Literature Review for Preterm Birth and Infant Mortality

Prepared for
Cradle Cincinnati Advisory Board
Oct 26, 2017
 TABLE OF CONTENTS
Click on links below to access full texts and documents, unless indicated otherwise.

WHAT WE KNOW ABOUT RISKS FOR PRETERM BIRTH

INTRODUCTION TO PRETERM BIRTH

Epidemiology and causes of preterm birth

LITERATURE – PRETERM BIRTH, STRONG EVIDENCE

SHORT CERVIX | ABSTRACT |
Health disparities in risk for cervical insufficiency
INADEQUATE PRENATAL CARE | ABSTRACT |
Inadequate Prenatal Care Utilization and Risks of Infant Mortality and Poor Birth Outcome: A
Retrospective Analysis of 28,729,765 U.S. Deliveries over 8 Years
PREVIOUS PRETERM BIRTH | ABSTRACT |
The Preterm Prediction Study: Effect of gestational age and cause of preterm birth on subsequent
obstetric outcome
MOM’S MEDICAL ISSUES | ABSTRACTS |
Prepregnancy Health Status and the Risk of Preterm Delivery
Prepregnancy Weight and Pregnancy Outcome
DISPARITY / RACISM | ABSTRACTS |
Racial Discrimination and the Black-White Gap in Adverse Birth Outcomes: A Review
Closing the Black-White Gap in Birth Outcomes: A Life-course Approach
Discrimination and racial disparities in health: evidence and needed research
Very Low Birthweight in African American Infants: The Role of Maternal Exposure to Interpersonal
Racial Discrimination
BEING UNDERWEIGHT | ABSTRACT |
The Preterm Prediction study: Association between maternal body mass index and spontaneous and
indicated preterm birth
SHORT SPACING | ABSTRACTS |
Birth Spacing and Risk of Adverse Perinatal Outcomes: A Meta-analysis
Interpregnancy interval and risk of preterm birth and neonatal death: retrospective cohort study
SMOKING | ABSTRACTS |
Relationship of trimester-specific smoking patterns and risk of preterm birth
Self-reported and laboratory evaluation of late pregnancy nicotine exposure and drugs of abuse
Association of Reported Trimester-Specific Smoking Cessation and Fetal Growth Restriction
Smoking in pregnancy revisited: Findings from a large population-based study
 To access the full text of the articles on this page, please download Part 2 of the Literature Review.

LITERATURE – PRETERM BIRTH, MIXED EVIDENCE

FATHER INVOLVEMENT | ABSTRACTS |
Assessing the Impact of Paternal Involvement on Racial/Ethnic Disparities in Infant Mortality Rates
Paternal support and preterm birth, and the moderation of effects of chronic stress: a study in Los
Angeles County mothers
The Effects of Father Involvement during Pregnancy on Receipt of Prenatal Care and Maternal Smoking
WORKING CONDITIONS | ABSTRACTS |
Physical Exertion at Work and the Risk of Preterm Delivery and Small-for-Gestational-Age Birth
Employment, working conditions, and preterm birth: results from the Europop case-control survey
Occupational fatigue and preterm premature rupture of membranes
SOCIAL SUPPORT | ABSTRACTS |
Perceived social support interacts with prenatal depression to predict birth outcomes
Maternal Social Support and Neighborhood Income Inequality as Predictors of Low Birth Weight and
Preterm Birth Outcome Disparities: Analysis of South Carolina Pregnancy Risk Assessment and
Monitoring System Survey, 2000–2003
Support during pregnancy for women at increased risk of low birthweight babies (Review)
Social Capital, Income Inequality, and Mortality
UNINTENDED PREGNANCY | ABSTRACTS |
The Effects of Unintended Pregnancy on Infant, Child, and Parental Health: A Review of the Literature
Unintended pregnancy and preterm birth
UNSAFE OR UNSTABLE HOUSING | ABSTRACTS |
From Redlined to Evicted: Understanding The Relationship Between Housing & Maternal Health
Housing influences among sleep-related infant injury deaths in the USA
Housing Transitions and Low Birth Weight Among Low-Income Women: Longitudinal Study of the
Perinatal Consequences of Changing Public Housing Policy
Adverse perinatal outcomes associated with homelessness and substance use in pregnancy
Severity of Homelessness and Adverse Birth Outcomes
MOM’S AGE GREATER THAN 35 | ABSTRACT |
Effects of Maternal Age and Age-Specific Preterm Birth Rates on Overall Preterm Birth Rates — United
States, 2007 and 2014
MOM’S STRESS | ABSTRACTS |
Maternal Adverse Childhood Experience and Infant Health: Biomedical and Psychosocial Risks as
Intermediary Mechanisms
The Effect of Maternal Stress on Birth Outcomes: Exploiting a Natural Experiment
Maternal Stress and Preterm Birth
The preterm prediction study: Maternal stress is associated with spontaneous preterm birth at less
than thirty-five weeks' gestation
 To access the full text of the articles on this page, please download Part 3 of the Literature Review.

LITERATURE – SOCIAL DETERMINANTS, ROLE IN PERTERM BIRTH | ABSTRACTS |

A Communicative Model of Mothers’ Lifestyles During Pregnancy with Low Birth Weight Based on
Social Determinants of Health: A Path Analysis
Living in stressful neighbourhoods during pregnancy: an observational study of crime rates and birth
outcomes
The role of social determinants in explaining racial/ethnic disparities in perinatal outcomes
Risk Prediction for Adverse Pregnancy Outcomes in a Medicaid Population
The Social Determinants of Infant Mortality and Birth Outcomes in Western Developed Nations: A
Cross-Country Systematic Review
LITERATURE – PRETERM BIRTH, GENERAL | ABSTRACTS |
Predicting preterm birth among participants of North Carolina’s Pregnancy Medical Home Program
A Case-Control Study of Preterm Delivery Risk Factors According to Clinical Subtypes and Severity
Predictive value of various risk factors for preterm labor
LITERATURE – SAFE SLEEP | ABSTRACTS |
New Frameworks for Understanding Sudden Unexpected Deaths in Infancy (SUDI) in Socially
Vulnerable Families
Race, Ethnicity, and SIDS
SIDS and Other Sleep-Related Infant Deaths: Updated 2016 Recommendations for a Safe Infant
Sleeping Environment
Relationship of Sudden Infant Death Syndrome to Maternal Smoking During and After Pregnancy
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What we know about risks for preterm birth – Strong Evidence

Factor Increased likelihood # of Hamilton County Women Notes
of preterm birth impacted annually
Twins, Triplets, Multiples 10X ~450 women “Nearly 60% of twins are born preterm.”
(OR 9.79)

Short Cervix 6X ~40 women “The shorter the cervix, the greater the risk.”
(OR 6.44)

Inadequate Prenatal Care 4X ~750 women not accessing care “Risk of prematurity, stillbirth, early and late
(OR 3.75)* before 3rd trimester neonatal death, and infant
death increased linearly with decreasing care.”

Previous Preterm Birth 4X ~790 women

(OR 3.65)

Mom’s Medical Issues 4X for Diabetes (3.64) ~975 women w/ diabetes “Thyroid disease, asthma, diabetes and
3X for Hypertension ~1575 women w/ hypertension hypertension are all associated with increased
(2.92) rates of preterm birth.”

Black racial disparity/racism 4X at <23 weeks** ~3700 women Not limited to socioeconomic status.
<2X at <28 weeks Disparity is biggest with earliest births.
High levels of reported racism seem to have an
impact where moderate levels do not.
Being Underweight 3X ~350 women “Obesity can be protective.”
(2.45)***

Short Spacing 2X at <6 months <6 months: ~575 women Potentially larger impact w/ earliest preterm.
<2X at <12 months <12 months: ~1875 women Potentially larger impact in African Americans.
(OR 1.39) Strong evidence at <6 months. Mixed at 6-18.

Smoking <2X (OR 1.40-1.50) ~2,000 women

Adapted from Epidemiology and causes of preterm birth by Goldenberg, et al & Predicting preterm birth among participants of North Carolina’s Pregnancy
Medical Home Program by Tucker, et al. Estimated number of women impacted from vital statistics, PRAMS, and national estimates for short cervix.
*Inadequate Prenatal Care Utilization and Risks of Infant Mortality and Poor Birth Outcome
**Local disparity
***A case-control study of preterm delivery risk factors according to clinical subtypes and severity
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What we know about risks for preterm birth – Mixed Evidence

Factor Increased likelihood of # of Hamilton County women Notes
preterm birth impacted annually

Father involvement 3X for infant death* Unknown Very limited research available
(OR 3.41) ~6000 unmarried births

Working conditions 2X Unknown “Working long hours and undertaking hard physical
(OR 2.38)** labor under stressful conditions are probably
associated.” Other studies find little impact.

Social Support 2X ~2200 women

(OR 1.90)*** (self-report from PRAMS)

Unintended Pregnancy 2X ~4700 women Some studies find an impact, others find none.
(OR 1.82)**** (self-report from PRAMS)

Unsafe or Unstable Housing <2X Unknown

(OR 1.46) ~2400 report fair or poor housing

Mom’s Age Greater than 35 <2X ~1100 women

(OR 1.38)

Mom’s Stress <2X Unknown (depends on specific Mixed results as to whether chronic or acute stress
(OR 1.16)***** definition of stress) matters more.

Mom’s Depression Unknown ~1,000 (self-report postpartum) Most studies show no impact on preterm birth.
Some show a small impact.

Infection / Inflammation Unknown Unknown “…studies suggest…infection might account for 25-40%
of preterm births.” Strong evidence that it matters;
little evidence that treatment improves risk.

Genetics Unknown Unknown Seems to play a role, but with many unknowns.
More research is needed.

Adapted from Epidemiology and causes of preterm birth by Goldenberg, et al & Predicting preterm birth among participants of North Carolina’s Pregnancy
Medical Home Program by Tucker, et al. Estimated number of women impacted from vital statistics, PRAMS, and Greater Cincinnati Health Status Survey.
*Assessing the Impact of Paternal Involvement on Racial/Ethnic Disparities in Infant Mortality Rates
**Predictive value of risk factors for preterm labor
***Maternal Social Support and Neighborhood Income Inequality as Predictors of Low Birth Weight and Preterm Birth Outcome Disparities
****Unintended Pregnancy and Preterm Birth
*****Maternal Stress is associated with spontaneous preterm birth at less than 35 weeks gestation
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INTRODUCTION TO PRETERM BIRTH

The following paper provides a general overview on preterm birth and discusses its various risk factors.
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Series

Preterm Birth 1
Epidemiology and causes of preterm birth
Robert L Goldenberg, Jennifer F Culhane, Jay D Iams, Roberto Romero

This paper is the first in a three-part series on preterm birth, which is the leading cause of perinatal morbidity and Lancet 2008; 371: 75–84
mortality in developed countries. Infants are born preterm at less than 37 weeks’ gestational age after: (1) spontaneous See Editorial page 2
labour with intact membranes, (2) preterm premature rupture of the membranes (PPROM), and (3) labour induction or This is the first in a Series of
caesarean delivery for maternal or fetal indications. The frequency of preterm births is about 12–13% in the USA and three papers about preterm birth
5–9% in many other developed countries; however, the rate of preterm birth has increased in many locations, Department of Obstetrics and
predominantly because of increasing indicated preterm births and preterm delivery of artificially conceived multiple Gynecology, Drexel
University College of Medicine,
pregnancies. Common reasons for indicated preterm births include pre-eclampsia or eclampsia, and intrauterine growth Philadelphia, PA, USA
restriction. Births that follow spontaneous preterm labour and PPROM—together called spontaneous preterm births—are (Prof R L Goldenberg,
regarded as a syndrome resulting from multiple causes, including infection or inflammation, vascular disease, and J F Culhane PhD); Department of
Obstetrics and Gynecology,
uterine overdistension. Risk factors for spontaneous preterm births include a previous preterm birth, black race,
Ohio State University,
periodontal disease, and low maternal body-mass index. A short cervical length and a raised cervical-vaginal fetal Columbus, OH, USA
fibronectin concentration are the strongest predictors of spontaneous preterm birth. (Prof J D Iams MD); Perinatology
Research Branch, National
Institute of Child Health and
Introduction all preterm births differs by ethnic group. Spontaneous
Human Development, National
Preterm deliveries are those that occur at less than preterm birth is most commonly caused by preterm Institutes of Health, Bethesda,
37 weeks’ gestational age; however, the low-gestational age labour in white women, but by PPROM in black women.8 MD and Detroit, MI, USA
cutoff, or that used to distinguish preterm birth from Preterm births can also be subdivided according to (Prof R Romero MD); and
Department of Obstetrics and
spontaneous abortion, varies by location. In the USA, the gestational age: about 5% of preterm births occur at less
Gynecology, Wayne State
preterm delivery rate is 12–13%; in Europe and other than 28 weeks’ (extreme prematurity), about 15% at 28–31 University, Detroit, MI, USA
developed countries, reported rates are generally 5–9%.1,2 weeks’ (severe prematurity), about 20% at 32–33 weeks’ (R Romero)
The preterm birth rate has risen in most industrialised (moderate prematurity), and 60–70% at 34–36 weeks’ Correspondence to:
countries, with the USA rate increasing from 9·5% in 1981 (near term). Prof Robert Goldenberg,
Department of Obstetrics and
to 12·7% in 2005 (figure 1),2 despite advancing knowledge Much of the increase in the singleton preterm birth rate
Gynecology, Drexel University
of risk factors and mechanisms related to preterm labour, is explained by rising numbers of indicated preterm births College of Medicine, 245 N
and the introduction of many public health and medical (figure 3).9 A high number of preterm multiple gestations 15th Street, 17th Floor,
interventions designed to reduce preterm birth.3 Potential associated with assisted reproductive technologies is also Room 17113, Philadelphia,
PA 19102, USA
methods used to reduce preterm birth will be discussed in an important contributor to the overall increase in preterm
rgoldenb@drexelmed.edu
the second paper in this series.4 births. Singleton pregnancies after in-vitro fertilisation are
Preterm births account for 75% of perinatal mortality also at increased risk of preterm birth.10 In the USA,
and more than half the long-term morbidity.5 Although increasing indicated preterm births mask a small, but
most preterm babies survive, they are at increased risk of
neurodevelopmental impairments and respiratory and 14
gastrointestinal complications. The outcome of preterm 13
births will be discussed in detail in the third paper in this 12
series.6 Here, we explore the epidemiology, causes, and 11
Proportion of preterm birth (%)

mechanisms leading to preterm births. 10

9
Epidemiology 8
7
The obstetric precursors leading to preterm birth are: (1)
6
delivery for maternal or fetal indications, in which labour
5
is either induced or the infant is delivered by prelabour 4
caesarean section; (2) spontaneous preterm labour with 3
intact membranes; and (3) preterm premature rupture of 2
the membranes (PPROM), irrespective of whether 1
delivery is vaginal or by caesarean section (figure 2).7 0
About 30–35% of preterm births are indicated, 40–45%
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follow spontaneous preterm labour, and 25–30% follow Year

PPROM; births that follow spontaneous labour and Figure 1: Percentage of all births classified as preterm in the USA, 1981–2004
PPROM are together designated spontaneous preterm Source: Martin JA, Kochanek KD, Strobino DM, Guyer B, MacDorman MF. Annual summary of vital statistics—2003.
births. The contribution of the causes of preterm births to Pediatrics 2005; 115: 619–34.

www.thelancet.com Vol 371 January 5, 2008 75

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Series
Delivery because of
Spontaneous maternal or fetal
preterm labour infections
30%
45%
25%
Premature preterm rupture
of the membranes (PPROM)
Preterm labour
Figure 2: Obstetric precursors of preterm birth
important, reduction in spontaneous preterm births,
especially in black women.11
PPROM is defined as spontaneous rupture of the
membranes at less than 37 weeks’ gestation at least 1 h
before the onset of contractions. The cause of membrane
rupture in most cases is unknown, but asymptomatic
intrauterine infection is a frequent precursor. Risk factors
for PPROM are generally similar to those for preterm
spontaneous labour with intact membranes, although
infections and tobacco exposure play important parts.12
Most women with PPROM begin labour spontaneously
within several days, but a small proportion of women
remains undelivered for weeks or months. Since the
membranes generally form a barrier to ascending infection,
a common complication of PPROM is development of
intrauterine infection and preterm labour.13
Preterm labour is usually defined as regular contractions
accompanied by cervical change at less than 37 weeks’
gestation. Pathogenesis of preterm labour is not well
understood, but preterm labour might represent early
idiopathic activation of the normal labour process or the
results of pathological insults. A role for the fetus in
determining the timing of the onset of labour has been
proposed on the basis of studies in sheep.14 Ablation of the
fetal hypophysis or adrenal glands, or both, prevents the
initiation of parturition; thus fetal cortisol is central to
labour initiation in sheep. The same mechanism might be
implicated in parturition in women, as suggested by
reports of protracted pregnancies with an anencephalic
fetus.15 Theories proposed to explain the initiation of term
labour are: (1) progesterone withdrawal, (2) oxytocin
initiation, and (3) decidual activation. The progesterone
withdrawal theory stems from studies in sheep.14,16 As
parturition nears, the fetal-adrenal axis becomes more
sensitive to adrenocorticotropic hormone, increasing the
secretion of cortisol. Fetal cortisol stimulates placental
76
17α-hydroxylase activity, which decreases progesterone
secretion and increases oestrogen production. The reversal
in the oestrogen/progesterone ratio results in increased
prostaglandin formation, initiating a cascade of events that
culminates in labour. In human beings, serum
progesterone concentrations do not fall as labour
approaches;16 however, because progesterone antag-
onists—such as RU486—initiate preterm labour and
progestational agents prevent preterm labour, a decrease
in local progesterone concentrations or in the number of
receptors is a plausible mechanism for initiation of
labour.16–18 Because intravenous oxytocin increases the
frequency and intensity of uterine contractions, the
assumption is that oxytocin plays a part in labour initiation.
However, blood concentrations of oxytocin do not rise
before labour and the clearance of oxytocin remains
constant; thus oxytocin is unlikely to initiate labour.
An important pathway leading to labour initiation
implicates inflammatory decidual activation.19 Although at
term, decidual activation seems to be mediated at least in
part by the fetal-decidual paracrine system (perhaps
through localised decreases in progesterone concen-
tration), in many cases of early preterm labour, decidual
activation seems to arise in the context of intrauterine
bleeding or an occult intrauterine infection.
Causes of preterm labour
Risk factors
Preterm labour is now thought to be a syndrome initiated
by multiple mechanisms, including infection or
inflammation, uteroplacental ischaemia or haemorrhage,
uterine overdistension, stress, and other immunologically
mediated processes.19 A precise mechanism cannot be
established in most cases; therefore, factors associated
with preterm birth, but not obviously in the causal pathway,
have been sought to explain preterm labour. An increasing
number of risk factors are thought to interact to cause a
transition from uterine quiescence toward preterm labour
or PPROM. Since many of the risk factors result in
increased systemic inflammation, increasing stimulation
of the infection or inflammation pathway might explain
some of the increases in preterm births associated with
multiple risk factors.20
Defining risk factors for prediction of preterm birth is a
reasonable goal for several reasons. First, identification of
at-risk women allows initiation of risk-specific treatment.21
Second, the risk factors might define a population useful
for studying specific interventions. Finally, identification
of risk factors might provide important insights into
mechanisms leading to preterm birth. There are many
maternal or fetal characteristics that have been associated
with preterm birth, including maternal demographic
characteristics, nutritional status, pregnancy history,
present pregnancy characteristics, psychological
characteristics, adverse behaviours, infection, uterine
contractions and cervical length, and biological and genetic
markers.21
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Series

Maternal risk factors A

In the USA and in the UK, women classified as black,
African-American, and Afro-Caribbean are consistently 12

reported to be at higher risk of preterm delivery: preterm

birth rates are in the range of 16–18% in black women
10
compared with 5–9% for white women. Black women are
also three to four times more likely to have a very early All preterm births

Preterm birth <37 weeks’ rate (%)

Spontaneous preterm birth
preterm birth than women from other racial or ethnic 8 Medically indicated
groups.22,23 Part of the discrepancy in preterm birth rates Ruptured membranes
between the USA and other countries might be explained
by the high rate of preterm births in the USA black 6

population. Over time, the disparity in preterm birth rates

between black and white women has remained largely 4
unchanged and unexplained, and contributes to a cycle of
reproductive disadvantage with far-reaching social and
medical consequences.24 East Asian and Hispanic women 2
typically have low preterm birth rates. Women from south
Asia, including the Indian subcontinent, have high rates of
0
low birthweight caused by decreased fetal growth, but
preterm delivery does not seem to be substantially
increased. Other maternal demographic characteristics B
associated with preterm birth include low socioeconomic
50
and educational status, low and high maternal ages, and
single marital status.25–27 The mechanisms by which the 40
maternal demographic characteristics are related to
Change in preterm birth rate relative to 1989 (%)

Medically indicated
preterm birth are unknown. 30 All preterm births
Observational studies of the type of work and physical Spontaneous preterm birth
Ruptured membranes
activity related to preterm birth have produced conflicting 20

results.28–31 Investigation of work-related risk is made

10
difficult by confounding factors; however, even after
accounting for population differences, working long hours 0
and undertaking hard physical labour under stressful
conditions are probably associated with an increase in –10
preterm birth. The level of physical activity is not
consistently related to the rate of preterm birth. –20
Whether differences in demographic, social, or economic
–30
risks, frequent absence of health insurance, and absence
of a strong supportive economic and social safety net –40
contribute to the disparity in preterm birth rates between 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001
the USA and other developed countries is unknown. Lower Year
gestational age cutoffs for defining preterm birth used in
Figure 3: Temporal changes in singleton preterm births overall and temporal changes resulting from ruptured
the USA might explain part of the difference in preterm membranes, medically indicated preterm labour, and spontaneous preterm labour in USA, 1989–2000
birth rates. What does seem clear, however, is that in many A) Rates in each group by year. B) The percentage change in rates relative to 1989. Figure adapted from reference 9.
USA immigrant groups, the greater the length of time
spent living in the USA, the higher the preterm birth rate; previous pregnancy. Maternal depletion might be another
the explanation for this finding is also unknown. cause because pregnancy consumes maternal stores of
There is a raised risk of preterm birth in pregnancies essential vitamins, minerals, and aminoacids. A short
arising within close temporal proximity to a previous interval decreases the opportunity to replenish these
delivery.32 An interpregnancy interval of less than 6 months nutrients.
confers a greater than two-fold increased risk of preterm Nutritional status during pregnancy can be described by
birth after adjustment for confounding variables.33 indicators of body size such as body-mass index (BMI),
Furthermore, women whose first birth was preterm are far nutritional intake, and serum assessments for various
more likely to have a short interval than women who had a analytes.34–36 For example, a low prepregnancy BMI is
term first birth, thus compounding the risk. Although the associated with a high risk of spontaneous preterm birth,
mechanism is not clear, one potential explanation is that whereas obesity can be protective (figure 4).35 Women with
the uterus takes time to return to its normal state, including low serum concentrations of iron, folate, or zinc have more
resolution of the inflammatory status associated with the preterm births than those with measurements within the

www.thelancet.com Vol 371 January 5, 2008 77


Series
18
16·6
15
Proportion of preterm births (%)
12 11·3
9 for the rate of increased spontaneous preterm births.19
6 5·8
4·8
3·7
3
0 amniotic fluid—polyhydramnios or oligohydramnios—are
<19 19–24·9
Figure 4: Comparison of spontaneous and indicated preterm birth by
maternal body-mass index (BMI)
Figure adapted from reference 35.
normal range.34,36 There are many potential mechanisms
by which maternal nutritional status might affect preterm
birth—eg, spontaneous preterm birth can be caused by
maternal thinness associated with decreased blood volume
and reduced uterine blood flow.37 Thin women might also
consume fewer vitamins and minerals, low concentrations
of which are associated with decreased blood flow and
increased maternal infections.37,38 Obese women are more
likely to have infants with congenital anomalies, such as
neural-tube defects, and these infants are more likely to be
delivered preterm.39 Obese women are also more likely to
develop pre-eclampsia and diabetes, and have indicated
preterm births associated with these disorders.
Pregnancy history
The recurrence risk in women with a previous preterm
delivery ranges from 15% to more than 50%, dependent on
the number and gestational age of previous deliveries.
Mercer and colleagues40 reported that women with previous
preterm deliveries had a 2·5–fold increased risk in their
next pregnancy. The risk of another preterm birth is
inversely related to the gestional age of the previous
preterm birth. The mechanism for the recurrence is not
always clear, but women with early spontaneous preterm
births are far more likely to have subsequent spontaneous
preterm births; women with indicated preterm births tend
to repeat such births.41,42 Persistent or recurrent intrauterine
infections probably explain many repetitive spontaneous
preterm births.41 The underlying disorder causing indicated
preterm births, such as diabetes, hypertension, or obesity,
frequently persists between pregnancies.
Pregnancy characteristics
Multiple gestations—accounting for only 2–3% of
infants—carry a substantial risk of preterm delivery, and
result in 15–20% of all preterm births. Nearly 60% of twins
78
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are born preterm. About 40% of twins will have spontaneous
labour or PPROM before 37 weeks’ gestation, with others
Spontaneous preterm births
Indicated preterm births having an indicated preterm delivery because of
pre-eclampsia, or other maternal or fetal disorders. Nearly
all higher multiple gestations will result in preterm
delivery. Uterine overdistension, resulting in contractions
and PPROM, is believed to be the causative mechanism
8·1
7·1 Vaginal bleeding caused by placental abruption or
placenta preavia is associated with a very high risk of
5·2
preterm delivery, but bleeding in the first and second
4·1 3·8
trimesters that is not associated with either placental
abruption or placenta preavia is also associated with
subsequent preterm birth.43 Extremes in the volume of
25–29·9 30–34·9 ≥35
associated with preterm labour and PPROM. Maternal
BMI kg/m² abdominal surgery in the second and third trimesters can
stimulate contractions culminating in preterm delivery.
Maternal medical disorders, such as thyroid disease,
asthma, diabetes, and hypertension, are associated with
increased rates of preterm delivery, many of which are
indicated because of maternal complications. History of
cervical cone biopsy sample or loop electrocautery excision
procedures secondary to premalignant cervical disorders
have also been associated with an increase in spontaneous
preterm delivery, as have various anomalies of the uterus
itself—such as the presence of a septum.44
Mothers experiencing high levels of psychological or
social stress are at increased risk of preterm birth (generally
<2–fold) even after adjustment for the effects of
sociodemographic, medical, and behavioural risk factors.45,46
Furthermore, exposure to objectively stressful conditions,
such as housing instability and severe material hardship,
has also been associated with preterm birth.47 Although the
mechanism underlying the association between
psychological or social stress and increased risk of preterm
birth is unknown, a role for corticotropin releasing
hormone has been proposed. 48–50 Women exposed to
stressful conditions also have increased serum concen-
trations of inflammatory markers—such as C-reactive
protein—an observation not accounted for by other
established risk factors for inflammation.51 These findings
suggest that systemic inflammation might be a pathway by
which stress could increase the risk of preterm birth.
Clinical depression during pregnancy has been reported
in up to 16% of women, with up to 35% having some
depressive symptoms.52,53 Although the results are
inconsistent, several reports suggest a relation (risks
generally rose <2–fold) between depression and preterm
birth.54–55 Depression is associated with an increase in
smoking, and drug and alcohol use; therefore, the relation
between depression and preterm birth might be mediated
by these behaviours.56–58 Nevertheless, in some studies that
adjusted for smoking and drug and alcohol use, the
association between depression and preterm birth
persisted, suggesting that this relationship might be
caused by more than confounding. Although, the
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mechanism(s) underlying the association of depression
and preterm birth is unknown, there is an association
between depressed mood and a reduction in natural killer
cell activity, and higher plasma concentrations of pro-
inflammatory cytokines and their receptors.59 Inflam-
mation, therefore, might also partly mediate the relation
between depression and preterm birth.
In the USA, about 20–25% of pregnant women smoke,
and, of these, 12–15% continue throughout pregnancy.60–62
Tobacco use increases the risk of preterm birth (<2–fold)
after adjustment for other factors.61,62 The mechanism(s) by
which smoking is related to preterm birth is unclear. There
are more than 3000 chemicals in cigarette smoke and the
biological effects of most are unknown;63 however, both
nicotine and carbon monoxide are powerful
vasoconstrictors, and are associated with placental damage
and decreased uteroplacental blood flow. Both pathways
lead to fetal growth restriction and indicated preterm
births. Smoking is also associated with a systemic
inflammatory response and can increase spontaneous
preterm birth through that pathway.64,65 Although heavy
alcohol consumption has been associated with preterm
birth, neither mild nor moderate alcohol use is generally
regarded as a risk factor for preterm birth. Cocaine and
heroin use have been associated with preterm birth in
several studies.
Intrauterine infection is a frequent and important
mechanism leading to preterm birth.66,67 The mechanisms
by which intrauterine infections lead to preterm labour are
related to activation of the innate immune system.68
Microorganisms are recognised by pattern-recognition
receptors—eg, toll-like receptors, which in turn elicit the
release of inflammatory chemokines and cytokines—such
as interleukin 8, interleukin 1β, and tumour necrosis factor
(TNF) α. Microbial endotoxins and proinflammatory
cytokines stimulate the production of prostaglandins,
other inflammatory mediators, and matrix-degrading
enzymes. Prostaglandins stimulate uterine contractility,
whereas degradation of extracellular matrix in the fetal
membranes leads to PPROM.67,68
Microbiological studies suggest that intrauterine
infection might account for 25–40% of preterm births;67
however, 25–40% might be a minimum estimate because
intrauterine infection is difficult to detect with conventional
culture techniques.69 Several investigators have shown
additional microbial footprints in the amniotic cavity by
using molecular microbiological techniques70–72—eg,
women with a positive amniotic fluid Ureaplasma
urealyticum PCR, but a negative culture, have similar rates
of preterm birth to women with positive cultures for the
same microorganism.73 Furthermore, since the rate of
microbial colonisation of the chorioamnion is twice that
seen in the amniotic cavity, rates of intrauterine infection
based only on amniotic fluid cultures substantially
underestimate the level of association.74
Accumulating evidence suggests that intra-amniotic
infection is a chronic process.67 Women with positive
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Series
U urealyticum amniotic fluid cultures or who are
PCR-positive for U urealyticum at the time of midtrimester
genetic amniocentesis often have spontaneous preterm
labour or PPROM weeks after the procedure.75–77
Importantly, the earlier the gestational age at which women
present with preterm labour, the higher the frequency of
intrauterine infection.78,79 At 21–24 weeks’ gestation, most
spontaneous births are associated with histological
chorioamnionitis compared with about 10% at
35–36 weeks.78,79
The microorganisms most commonly reported in the
amniotic cavity are genital Mycoplasma spp, and,
specifically, U urealyticum, but many other organisms have
been identified.80–83 Some common lower genital tract
microorganisms, such as Streptococcus agalactiae, are rarely
seen in the amniotic cavity before membrane rupture.67,84
The genital mycoplasmas and other organisms detected in
the uterus before membrane rupture are typically of low
virulence, probably accounting for both the chronicity of
intrauterine infections and the frequent absence of overt
clinical signs of infection.67
Intrauterine infection can be confined to the decidua,
extend to the space between the amnion and chorion, and
reach the amniotic cavity and the fetus.67,68 The amniotic
cavity is usually sterile for bacteria, but the significance of
microorganisms in the membranes is less clear. Bacteria
have been cultured from the chorioamnion in 15% of
non-labouring women with intact membranes undergoing
indicated caesarean delivery.67 Fluorescence in-situ
hybridisation with a DNA probe specific for conserved
regions of bacterial DNA (the 16S ribosomal RNA) has
detected bacteria in the membranes of up to 70% of women
undergoing elective caesarean section at term.85 These
findings suggest that the presence of bacteria in the
chorioamnion alone cannot be sufficient to cause an
inflammatory response, preterm labour, and preterm
birth.85 Nevertheless, bacteria in the membranes and an
associated inflammatory response in the amniotic fluid
have been identified in more than 80% of women in early
preterm labour with intact membranes who underwent
caesarean section.68 Thus, bacterial infection probably
predisposes to preterm birth.
Microorganisms can gain access to the amniotic cavity
by: (1) ascending from the vagina and the cervix;
(2) haematogenous dissemination through the placenta;
(3) accidental introduction at the time of invasive
procedures; and (4) by retrograde spread through the
fallopian tubes (figure 5).67,86 The most common pathway is
the ascending route. Although most investigators believe
that ascent happens during the second trimester, the
timing is unknown; some women have asymptomatic
endometrial colonisation before pregnancy.87 Irrespective
of when colonisation occurs, the hypothesis is that only
when the membranes become tightly applied to the
decidua at about 20 weeks’ gestation, essentially forming
an abscess, do colonised women become symptomatic and
progress to early preterm birth.67
79
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Series
Retrograde from
abdominal cavity
Amniocentesis
Haematogeneously
through placenta
Ascending from vagina
Figure 5: Potential routes of intrauterine infection
The most advanced and serious stage of ascending
intrauterine infection is fetal infection. Carroll and
colleagues88 reported that fetal bacteraemia is present in
33% of fetuses with positive amniotic fluid cultures versus
4% with negative cultures. In another study, genital
mycoplasma species were detected in 23% of umbilical
cord cultures from infants born at less than 32 weeks’
gestation.89 Both studies suggest that subclinical fetal
infection is far more common than traditionally recognised.
Microbial invasion of the amniotic cavity is frequently
associated with intra-amniotic inflammation and a fetal
inflammatory response.90,91 The fetal inflammatory
response has been linked to the onset of preterm labour,
and fetal injury and long-term handicap—including
periventricular leucomalacia, cerebral palsy, and chronic
lung disease.92–94
Bacterial vaginosis—a disorder defined by a change in
the microbial ecosystem of the vagina—is diagnosed
clinically by the presence of clue cells, a vaginal pH greater
than 4·5, a profuse white discharge, and a fishy odour
when the vaginal discharge is exposed to potassium
hydroxide.95 In the laboratory, bacterial vaginosis is defined
by the Nugent criteria in which gram-stained smears are
scored on the basis of numbers of lactobacilli, which tend
to be low, and the presence of organisms resembling
mobiluncus and bacteroides, the numbers of which tend
to be high.96 A score of 7–10 is used to diagnose bacterial
vaginosis, and has been associated with a 1·5-fold to 3-fold
increase in the rate of preterm birth.97,98 Black women in
80
both the USA and the UK are three times more likely to
have bacterial vaginosis than are white women, and this
difference might explain 50% of the excess preterm births
in black women.21,99,100 The mechanism by which bacterial
vaginosis is associated with preterm birth is unknown, but
microorganisms that cause the infection probably ascend
into the uterus before or early during pregnancy.101,102
Whether other genital infections are causally associated
with preterm birth is not always clear.103,104 For many
infections, a range of associations has been reported,
varying from none to strong. Women with genital
infections generally have other risk factors, and many
studies have not considered confounding variables.
Nevertheless, trichomoniasis seems to be associated with
preterm birth with a relative risk (RR) of about 1·3.105
Chlamydia is probably associated with preterm birth only
in the presence of a maternal immune response, and most
probably with a RR of about 2.106 Syphilis and gonorrhoea
are probably associated with preterm birth with a RR of
about 2.107 Vaginal group B streptococcus, U urealyticum,
and M hominus colonisations are not associated with
increased risk of preterm birth.103,104
Several non-genital tract infections, such as pyelonephritis
and asymptomatic bacteriuria, pneumonia, and
appendicitis, are associated with, and probably predispose
to, preterm birth.103,108 Periodontal disease has received
widespread scrutiny with some case-control studies
suggesting an increased risk independent of other
factors.109,110 One potential explanation for the relation is
that gingival crevice organisms, by way of maternal
bacteraemia and transplacental passage, result in an
intrauterine infection;111 however, after adjustment for
other factors, periodontal disease associated with preterm
birth was not related to increased intrauterine bacterial
colonisation or histological chorioamnionitis.112 The
biological pathway underlying the relation between
periodontal disease and preterm births remains elusive.
Compared with bacterial infections, there is sparse
evidence that viral infections predispose to preterm birth;
however, when the mother is severely ill, such as with
varicella pneumonia or severe acute respiratory syndrome,
a preterm delivery might occur.113,114 In several studies, the
viral DNAs—identified by PCR techniques—in the
amniotic fluid of asymptomatic women undergoing
genetic amniocentesis were generally unrelated to
subsequent preterm births;115 therefore, it seems unlikely
that maternal viral infection plays an important part in
preterm birth, but controversy persists, and with little
information, further study is needed.116
Several studies have shown an association between
uterine contraction frequency and preterm birth;117–119
however, uterine contractions do not predict preterm birth
well in singletons because of the wide variation in
frequency in normal pregnancy and the large overlap in
frequency between women who do and do not deliver
preterm.119 Newman and colleagues120 reported similar
results in a study in twins; however, women admitted with
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 RETURN TO TABLE OF CONTENTS
a diagnosis of preterm labour, if they do not deliver, remain
at increased risk of subsequent preterm labour and
PPROM.
As labour approaches, the cervix shortens, softens,
rotates anteriorly, and dilates. Both digital and ultrasound
examinations of the cervix have shown that cervical
shortening is a risk factor for preterm delivery.121–123
Ultrasound has proven especially useful in two
circumstances: the first is in asymptomatic women,
whereas the second is in those presenting with contractions.
In asymptomatic women, at 24 weeks’ gestation, a cervical
length of less than 25 mm defines increased risk of preterm
birth. The shorter the cervix, the greater the risk.122,123
Women with preterm contractions often present a clinical
dilemma, since nearly 60% of such women will, without
treatment, deliver at term. Such women are usually
observed for several hours before a decision is made to
initiate tocolytic treatment, give corticosteroids, or
discharge the patient. Cervical length can discriminate
between women not in labour and those who carry a
pronounced risk of early delivery. With a cervical length
greater than 30 mm, the likelihood of delivering in the next
week is about 1%, and most women can be safely
discharged without treatment.124
Cervical insufficiency caused by congenital cervical
weakness, surgery, or trauma has been implicated as causal
for some preterm births; however, distinguishing cervical
insufficiency from cervical shortening attributable to other
causes has proven difficult, and the exact contribution to
preterm birth is unknown.125
Biological and genetic markers
Biological fluids (eg, amniotic fluid, urine, cervical mucus,
vaginal secretions, serum or plasma, or both, and saliva)
have been used to assess the value of biomarkers for the
prediction of preterm birth.21,126 Cytokines, chemokines,
oestriol, and other analytes have been assessed, and many,
especially those related to inflammation, are associated
with preterm birth.. Studies of biomarkers have improved
the understanding of the mechanisms of disease leading
to spontaneous preterm birth, but few biomarkers have
shown clinical usefulness.21 An important consideration is
that, besides the specific nature of the analyte and its
origin, an understanding of timing related to gestational
age of collection and delivery is also necessary. For example,
the concentration of matrix metalloproteinase-9 in serum
rises substantially about 24 h before labour initiation.127
Such late prediction is of little value in prevention, but can
aid in understanding the pathophysiology of preterm
labour. Salivary oestriol concentration predicts late preterm
birth quite well, but is not especially useful for the
prediction of earlier preterm births.128 Prediction of late
preterm births is of little importance because morbidity in
these births is low.
The most powerful biochemical preterm birth predictor
identified to date is fetal fibronectin—a glycoprotein that
when present in cervicovaginal fluid is a marker of
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Series
choriodecidual disruption.129 Typically, fetal fibronectin is
absent from cervicovaginal secretions from 24 weeks’
until near term; however, 3–4% of women undergoing
routine screening at 24–26 weeks’ are positive, and are at
substantially increased risk of preterm delivery. For
clinical care, an important characteristic of the fetal
fibronectin test is its negative predictive value. In
questionable cases of preterm labour, only about 1% of
women with a negative test deliver in the next week.130
Each mechanism of disease responsible for preterm
labour and PPROM has the potential for a genetic
component. Women with sisters who gave birth pre-
term have an 80% higher risk of delivering preterm
themselves.131 Grandparents of women having a pre-
term birth are significantly more likely to have been born
preterm themselves.132 Genetic association studies have
been used to identify single-nucleotide polymorphisms
in several genes associated with preterm labour and
PPROM.133–135 The fetal and maternal genotypes modify
the risk of preterm delivery.135 A gene-environment
interaction has been shown with maternal carriage of an
allele of the TNFα gene and bacterial vaginosis.136
Although neither characteristic alone was associated with
spontaneous preterm birth, the combination increased
the risk of preterm birth. Similarly, maternal carriage of a
polymorphism in the IL6 gene did not result in increased
risk of spontaneous preterm birth for white or black
women;137 however, black women who were carriers of
the IL6 allele and had bacterial vaginosis had a
two-fold greater risk of preterm birth than did those who
carried the variant but did not have such infection. An
interaction between maternal smoking and gene
polymorphism on birthweight has also been described.138
The data provide evidence for gene-environment
interactions in spontaneous preterm birth. Technological
advances and completion of the HapMap project have
made possible the conduction of whole-genome association
studies;139 therefore, genetics is evolving from a candidate
gene approach in which the DNA variants of biologically
interesting genes are studied to a true genomic approach
that aims to examine the entire genome. High-density
arrays now allow simultaneous examination of 500 000 or
more DNA variants in the same individual. Such studies
have not been undertaken in relation to preterm birth.
The proteome is the entire set of proteins encoded by
the genome, and proteomics is the study of the global set
of proteins.140 Analysis of amniotic fluid and serum from
women with preterm labour and PPROM has been
undertaken to identify biomarkers for preterm labour
and PPROM. In one study, bacteria were inoculated into
the amniotic fluid of rhesus monkeys and the proteomic
response monitored over time;141 several novel infection
markers were identified. The same proteins were
identified in amniotic fluid of pregnant women with
chorioamnionitis-associated preterm labour. Thus, pro-
teomic techniques can be used to identify biomarkers in
women with premature labour and PPROM.
81
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Series
Additional research that clearly defines the mechanisms
by which risk factors are related to preterm birth is crucial.
Improved understanding of these mechanisms should
allow clinicians to design appropriate interventions so that
the incidence of preterm birth and related fetal and
neonatal morbidity and mortality will be reduced.
Conflict of interest statement
We declare that we have no conflict of interest.
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87 Andrews WW, Goldenberg RL, Hauth JC, Cliver SP, Conner M,
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88 Carroll SG, Papaioannou S, Ntumazah IL, Philpott-Howard J,
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90 Gomez R, Romero R, Ghezzi F, Yoon BH, Mazor M, Berry SM.
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91 Romero R, Gomez R, Ghezzi F, et al. A fetal systemic inflammatory
response is followed by the spontaneous onset of preterm parturition.
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92 Yoon BH, Romero R, Yang SH, et al. Interleukin-6 concentrations in
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83
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94 Yoon BH, Romero R, Kim KS, et al. A systemic fetal inflammatory
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95 Amstel R, Totten PA, Speigel CA, et al. Nonspecific vaginitis:
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96 Nugent RP, Krohn MA, Hillier SL. Reliability of diagnosing bacterial
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97 Meis PJ, Goldenberg RL, Mercer B, et al. The preterm prediction
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98 Hillier SL, Nugent RP, Eschenbach DA, et al. Association between
bacterial vaginosis and preterm delivery of a low-birthweight infant.
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1995; 333: 1737–42.
99 Goldenberg RL, Klebanoff MA, Nugent R, et al. Bacterial colonization
of the vagina during pregnancy in four ethnic groups.
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100 Fiscella, K. Racial disparities in preterm births. The role of urogenital
infections. Public Health Rep 1996; 111: 104–13.
101 Krohn MA, Hillier SL, Nugent RP, et al. The genital flora of women
with intraamniotic infection. J Infect Dis 1995; 171: 1475–80.
102 Hillier SL, Krohn MA, Cassen E, et al. The role of bacterial vaginosis
and vaginal bacteria in amniotic fluid infection in women in preterm
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103 Goldenberg RL, Culhane JF, Johnson DC. Maternal infection and
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104 Goldenberg RL, Andrews WW, Yuan AC, et al. Sexually transmitted
diseases and adverse outcomes of pregnancy. Clin Perinatol 1997;
24: 23–41.
105 Cotch MF, Pastorek JG 2nd, Nugent RP, et al. Trichomonas vaginalis
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106 Sweet RL, Landers DL, Walker C, et al. Chlamydia trachomatis infection
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107 Donders GG, Desmyter J, De Wet DH, et al. The association of
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109 Offenbacher S, Katz V, Fertik G, et al. Periodontal infection as a
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110 Jeffcoat MK, Geurs NC, Reddy MS, Cliver SP, Goldenberg RL,
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111 Offenbacher S, Jared HL, O’Reilly PG, et al. Potential pathogenic
mechanisms of periodontitis associated pregnancy complications.
Ann Periodontol 1998; 3: 233–50.
112 Goepfert AR, Jeffcoat M, Andrews WW, et al. Periodontal disease and
upper genital tract inflammation in early spontaneous preterm birth.
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115 Wenstrom KD, Andrews WW, Bowles NE, et al. Intrauterine viral
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121 Copper RL, Goldenberg RL, Davis RO, et al. Warning symptoms,
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122 Iams, JD, Goldenberg RL, Meis PJ, et al. The length of the cervix and
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124 Leitich H, Brumbauer M, Kaider A, et al. Cervical length and dilation
of the internal as detected by vaginal ultrasonography as markers for
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continuum: a study of ultrasonographic cervical length and obstetric
performance. Am J Obstet Gynecol 1995; 172: 1097–103.
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www.thelancet.com Vol 371 January 5, 2008
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ABSTRACTS
LITERATURE – PRETERM BIRTH, STRONG EVIDENCE

There is strong evidence that the following risk factors contribute to preterm birth.
• Short cervix
• Inadequate prenatal care
• Previous preterm birth
• Mom’s medical issues
• Black racial disparity/racism
• Being underweight
• Short spacing
• Smoking
This section includes abstracts of the literature reviewed for the risk factors above.

Click on the individual risk factors above to view the corresponding abstracts.
Click on the article titles to access full text in the following pages.
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Factor Increased # of Hamilton County Notes

likelihood Women impacted
of preterm annually
birth

Short Cervix 6X ~40 women “The shorter the cervix, the

(OR 6.44) greater the risk.”

Health disparities in risk for cervical insufficiency (Human Reproduction, 2010)

Background: The purpose of the study was to examine racial/ethnic differences in cervical insufficiency risk.
Methods: We used the US 2005 Natality data file. Analysis was limited to singleton births. The prevalence of
cervical insufficiency was examined by the maternal characteristic for each racial group. Unconditional logistic
regression modeling was used to assess the association between race and cervical insufficiency while
controlling for confounders.
Results: Cervical insufficiency risk for Black women was more than twice that for their White counterparts
[odds ratio (OR) (95% confidence interval (CI)) of 2.45 (2.22–2.71)]. Prior pregnancy termination showed a
dose–response relationship with cervical insufficiency. Compared with women with no history of prior
pregnancy termination, primiparous women who have had one pregnancy termination had an OR (95% CI) of
2.49 (2.23–2.77). The OR for two, three and four or more terminations were 4.66 (4.07–5.33), 8.07 (6.77–9.61)
and 12.36 (10.19–15.00), respectively. Other predictors of cervical insufficiency included previous preterm
birth, parity, marital status, renal disease, history of diabetes, polyhydramnios and anemia.
Conclusions: There were significant racial/ethnic disparities with Black women having increased cervical
insufficiency risk, independent of other studied factors. Prior pregnancy termination is also a major risk factor
for cervical insufficiency. The White/Black disparity is evident in both primiparous and multiparous women.
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Factor Increased # of Hamilton County Notes

likelihood Women impacted
of preterm annually
birth

Inadequate Prenatal Care 4X ~750 women not “Risk of prematurity, stillbirth,

(OR 3.75)* accessing care before early and late neonatal death,
3rd trimester and infant
death increased linearly with
decreasing care.”

Inadequate Prenatal Care Utilization and Risks of Infant Mortality and Poor Birth Outcome: A Retrospective
Analysis of 28,729,765 U.S. Deliveries over 8 Years (American Journal of Perinatology, 2012)
Objective: To evaluate the association between adequacy of prenatal care utilization and risk of fetal and
neonatal mortality and adverse outcomes.
Methods: We conducted a population-based cohort study using the Center for Disease Control and
Prevention’s Linked Birth-Infant Death and Fetal Death data on all deliveries in the United States between
1995 and 2002. Inclusion criteria were singleton births 22 weeks of gestation with no known congenital
malformation. Inadequate prenatal care was defined according to the Adequacy of Prenatal Care Utilization
Index, and its effect on fetal and neonatal death was estimated using unconditional logistic regression analysis
adjusting for maternal age, race, education, and other confounding variables.
Results: During our 8-year study period, 32,206,417 births occurred, 28,729,765 (89.2%) of which met
inclusion criteria. Inadequate prenatal care utilization occurred in 11.2% of expectant mothers, more
commonly among women ≤20 years, black non-Hispanic and Hispanic women, and those without high school
education. Relative to adequate care, inadequate care was associated with increased risk of prematurity 3.75
(3.73 to 3.77), stillbirth 1.94 (1.89 to 1.99), early neonatal dearth 2.03 (1.97 to 2.09), late neonatal death 1.67
(1.59 to 1.76), and infant death 1.79 (1.76 to 1.82).
Conclusion: Risk of prematurity, stillbirth, early and late neonatal death, and infant death increased linearly
with decreasing care. Given the population effect of this association, public health initiatives should target
program expansion to ensure timely and adequate access, particularly for women ≤20 years, Black non-
Hispanic and Hispanic women, and those without high school education.
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Factor Increased # of Hamilton County Notes

likelihood Women impacted
of preterm annually
birth

Previous Preterm Birth 4X ~790 women

(OR 3.65)

The Preterm Prediction Study: Effect of gestational age and cause of preterm birth on subsequent obstetric
outcome (American Journal of Obstetrics & Gynecology, 1999)
Objective: We sought to evaluate the association between prior spontaneous preterm delivery and
subsequent pregnancy outcome.
Study Design: A total of 1711 multiparous women with singleton gestations were prospectively evaluated at
23 to 24 weeks’ gestation. Prior pregnancies were coded for the presence or absence of a prior spontaneous
preterm delivery. If a prior spontaneous preterm delivery had occurred, the gestation of the earliest prior
delivery (13-22, 23-27, 28-34, and 35-36 weeks’ gestation) was recorded. Current gestations were categorized
as spontaneous preterm delivery at <28, <30, <32, <35, or <37 weeks’ gestation. The risk of spontaneous
preterm delivery in the current gestation was determined on the basis of the occurrence, gestational age, and
cause of the earliest prior spontaneous preterm delivery.
Results: The incidences of spontaneous preterm delivery before 28, 30, 32, 35, and 37 weeks’ gestation were
0.8%, 1.1%, 1.9%, 5.1%, and 11.9%, respectively. Those with a prior spontaneous preterm delivery carried a
2.5-fold increase in the risk of spontaneous preterm delivery in the current gestation over those with no prior
spontaneous preterm delivery (21.7% vs 8.8%; P ≤ .001). Gravid women with an early prior spontaneous
preterm delivery (23-27 weeks’ gestation) had a higher risk of recurrent spontaneous preterm delivery (27.1%
vs 8.8%; P ≤ .001). Prior spontaneous preterm delivery was more closely associated with subsequent early
spontaneous preterm delivery at <28 weeks’ gestation (relative risk, 10.6) than for spontaneous preterm
delivery overall (relative risk, 2.5). An early prior spontaneous preterm delivery (23-27 weeks’ gestation) was
most highly associated with early spontaneous preterm delivery (<28 weeks’ gestation) in the current
gestation (relative risk, 22.1). The relationship between prior spontaneous preterm delivery and current
outcome was not as strong for those with a very early spontaneous preterm delivery (13-22 weeks’ gestation).
Prior spontaneous preterm delivery caused by preterm premature rupture of the membranes and preterm
labor was significantly associated with similar outcomes in the current gestation (P < .001).
Conclusion: Prior spontaneous preterm delivery is highly associated with recurrence in the current gestation.
An early prior spontaneous preterm delivery is more predictive of recurrence and is most highly associated
with subsequent early spontaneous preterm delivery.
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Factor Increased # of Hamilton County Notes

likelihood Women impacted
of preterm annually
birth

Mom’s Medical Issues 4X for Diabetes ~975 women w/ “Thyroid disease, asthma,
(3.64) diabetes diabetes and hypertension are
3X for ~1575 women w/ all associated with increased
Hypertension hypertension rates of preterm birth.”
(2.92)

Prepregnancy Health Status and the Risk of Preterm Delivery (Archives of Pediatrics & Adolescent Medicine,
2005)
Background: Despite extensive evaluation, our understanding of risk factors for premature delivery is
incomplete.
Objective: To examine whether a woman’s health status and risk factors before pregnancy are associated with
a woman’s risk of preterm delivery, independent of risk factors that occur during pregnancy. Design, Setting,
and Participants: Prospective cohort of pregnant women in the San Francisco Bay area who delivered a
singleton infant (n=1619).
Main Outcome Measure: Preterm delivery (<37 weeks’ gestational age).
Results: Sociodemographic characteristics alone explained 13.0% of the risk of preterm delivery, whereas risk
factors that occurred before pregnancy explained 39.8% and risk factors that occurred during pregnancy
explained 47.1%. After we adjusted for sociodemographic characteristics, prepregnancy risk factors, and
pregnancy risk factors, women who reported poor physical function during the month before conception were
nearly twice as likely to experience a preterm delivery (odds ratio, 1.97;95%confidence interval, 1.18-3.30) as
women with better physical function.
Conclusion: A broader focus on the health of women prior to pregnancy may improve rates of preterm
delivery.

Prepregnancy Weight and Pregnancy Outcome (JAMA: Journal of the American Medical Association, 1996)
In this issue of THE JOURNAL, there are two articles that describe the relationship between maternal size and
a pregnancy with a neural tube defect (NTD).1,2 Both investigations are population-based, case-controlled
studies involving more than 500 NTD cases and controls. Information on maternal characteristics, including
pregnancy events, prepregnancy weight, and dietary intake, was obtained by in-person interviews with each
mother within 5 to 6 months of delivery. The risk of NTD-affected pregnancy was estimated after adjusting for
multiple confounders. These two groups of investigators independently reached a similar conclusion: women
who are obese (ie, women who have a body mass index [BMI] of >29 kg/m2 or body weight of more than 80
kg) at the beginning of pregnancy are more likely to have infants with NTDs and this association is
independent of folate intake. Since previous studies have indicated similar relationships,3,4 it is likely that this
association will hold up under further scrutiny.
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Factor Increased # of Hamilton County Notes

likelihood Women impacted
of preterm annually
birth

Black racial 4X at <23 ~3700 women Not limited to socioeconomic

disparity/racism weeks** status.
Disparity is biggest with earliest
<2X at <28
births.
weeks
High levels of reported racism
seem to have an impact where
moderate levels do not.

Racial Discrimination and the Black-White Gap in Adverse Birth Outcomes: A Review (Journal of Midwifery &
Women’s Health, 2011)
Introduction: The purpose of this integrative review was to evaluate what is known about the relationship
between racial discrimination and adverse birth outcomes.
Methods: A search of the Cumulative Index of Nursing and Allied Health Literature, MEDLINE, and PsycINFO
was conducted. The keywords used were: preterm birth, premature birth, preterm delivery, preterm labor,
low birth weight, very low birth weight, racism, racial discrimination, and prejudice. Ten research studies were
reviewed. All of the studies included African American women in their samples, were conducted in the United
States, and were written in English. We did not limit the year of publication for the studies. Data were
extracted based on the birth outcomes of preterm birth, low birth weight, or very low birth weight.
Results: A consistent positive relationship existed between perceptions of racial discrimination and preterm
birth, low birth weight, and very low birth weight. No relationship was found between racial discrimination
and gestational age at birth.
Discussion: Future research should explore the effects of racial discrimination as a chronic stressor
contributing to the persistent gap in birth outcomes between racial groups.
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Closing the Black-White Gap in Birth Outcomes: A Life-course Approach (Ethnicity & Disease, 2010)
In the United States, Black infants have significantly worse birth outcomes than White infants. Over the past
decades, public health efforts to address these disparities have focused primarily on increasing access to
prenatal care, however, this has not led to closing the gap in birth outcomes. We propose a 12-point plan to
reduce Black-White disparities in birth outcomes using a life-course approach. The first four points (increase
access to interconception care, preconception care, quality prenatal care, and healthcare throughout the life
course) address the needs of African American women for quality healthcare across the lifespan. The next four
points (strengthen father involvement, systems integration, reproductive social capital, and community
building) go beyond individual-level interventions to address enhancing family and community systems that
may influence the health of pregnant women, families, and communities. The last four points (close the
education gap, reduce poverty, support working mothers, and undo racism) move beyond the biomedical
model to address the social and economic inequities that underlie much of health disparities. Closing the
Black-White gap in birth outcomes requires a life course approach which addresses both early life
disadvantages and cumulative allostatic load over the life course.

Discrimination and racial disparities in health: evidence and needed research (Journal of Behavioral
Medicine, 2009)
This paper provides a review and critique of empirical research on perceived discrimination and health. The
patterns of racial disparities in health suggest that there are multiple ways by which racism can affect health.
Perceived discrimination is one such pathway and the paper reviews the published research on discrimination
and health that appeared in PubMed between 2005 and 2007. This recent research continues to document an
inverse association between discrimination and health. This pattern is now evident in a wider range of
contexts and for a broader array of outcomes. Advancing our understanding of the relationship between
perceived discrimination and health will require more attention to situating discrimination within the context
of other health-relevant aspects of racism, measuring it comprehensively and accurately, assessing its stressful
dimensions, and identifying the mechanisms that link discrimination to health.

Very Low Birthweight in African American Infants: The Role of Maternal Exposure to Interpersonal Racial
Discrimination (American Journal of Public Health, 2004)
Objectives: We determined whether African American women’s lifetime exposure to interpersonal racial
discrimination is associated with pregnancy outcomes.
Methods: We performed a case–control study among 104 African American women who delivered very low
birthweight (<1500 g) preterm (<37 weeks) infants and 208 African American women who delivered non–low-
birthweight (>2500g) term infants in Chicago, Ill.
Results: The unadjusted and adjusted odds ratio of very low birthweight infants for maternal lifetime exposure
to interpersonal racism in 3 or more domains equaled 3.2 (95% confidence intervals=1.5, 6.6) and 2.6 (1.2,
5.3), respectively. This association tended to persist across maternal sociodemographic, biomedical, and
behavioral characteristics.
Conclusions: The lifelong accumulated experiences of racial discrimination by African American women
constitute an independent risk factor for preterm delivery.
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Factor Increased # of Hamilton County Notes

likelihood Women impacted
of preterm annually
birth

Being Underweight 3X ~350 women “Obesity can be protective.”

(2.45)***

The Preterm Prediction study: Association between maternal body mass index and spontaneous and
indicated preterm birth (American Journal of Obstetrics & Gynecology, 2005)
Objective: The purpose of this study was to evaluate the relationship between prepregnancy maternal body
mass index and spontaneous preterm birth and indicated preterm birth.
Study design: This was a secondary analysis of the Maternal-Fetal Medicine Units Network, Preterm Prediction
study. Patients were classified into categories that were based on their body mass index. Rates of indicated
and spontaneous preterm birth were compared.
Results: Five hundred ninety-seven (20.5%) of 2910 women were obese. Obese women had fewer
spontaneous preterm births at <37 weeks of gestation (6.2% vs 11.2%; P < .001) and at <34 weeks of gestation
(1.5% vs 3.5%; P = .012). Women with a body mass index of <19 kg/m2 had 16.6% spontaneous preterm birth,
with a body mass index of 19 to 24.9 kg/m2 had 11.3% spontaneous preterm birth, with a body mass index of
25 to 29.9 kg/m2 had 8.1% spontaneous preterm birth, with a body mass index of 30 to 34.9 kg/m 2 had 7.1%
spontaneous preterm birth, and with a body mass index of ≥35 kg/m2 had 5.2% spontaneous preterm birth (P
< .0001). Indicated delivery was responsible for an increasing proportion of preterm births with increasing
body mass index (P = .001). Obese women had lower rates of cervical length <25 mm (5% vs 8%; P = .012).
Multivariable regression analysis confirmed a lower rate of spontaneous preterm birth in obese gravid women
(odds ratio, 0.57; 95% CI, 0.39-0.83; P = .003).
Conclusion: Obesity before pregnancy is associated with a lower rate of spontaneous preterm birth.
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Factor Increased # of Hamilton County Notes

likelihood Women impacted
of preterm annually
birth

Short Spacing 2X at <6 <6 months: ~575 Potentially larger impact w/

months women earliest preterm.
Potentially larger impact in
<2X at <12 <12 months: ~1875
African Americans.
months (OR women
Strong evidence at <6 months.
1.39)
Mixed at 6-18.

Birth Spacing and Risk of Adverse Perinatal Outcomes: A Meta-analysis (JAMA: Journal of the American
Medical Association, 2006)
Context: Both short and long interpregnancy intervals have been associated with an increased risk of adverse
perinatal outcomes. However, whether this possible association is confounded by maternal characteristics or
socioeconomic status is uncertain.
Objective: To examine the association between birth spacing and relative risk of adverse perinatal outcomes.
Data Sources: Studies published in any language were retrieved by searching MEDLINE (1966 through January
2006), EMBASE, ECLA, POPLINE, CINAHL, and LILACS, proceedings of meetings on birth spacing, and
bibliographies of retrieved articles, and by contact with relevant researchers in the field.
Study Selection: Included studies were cohort, cross-sectional, and case-control studies with results adjusted
for at least maternal age and socioeconomic status, reporting risk estimates and 95% confidence intervals (or
data to calculate them) of birth spacing and perinatal outcomes. Of 130 articles identified in the search, 67
(52%) were included.
Data Extraction: Information on study design, participant characteristics, measure of birth spacing used,
measures of outcome, control for potential confounding factors, and risk estimates was abstracted
independently by 2 investigators using a standardized protocol.
Data Synthesis: A random-effects model and meta-regression analyses were used to pool data from individual
studies. Compared with interpregnancy intervals of 18 to 23 months, interpregnancy intervals shorter than 6
months were associated with increased risks of preterm birth, low birth weight, and small for gestational age
(pooled adjusted odds ratios [95% confidence intervals]: 1.40 [1.24-1.58], 1.61 [1.39-1.86], and 1.26 [1.18-
1.33], respectively). Intervals of 6 to 17 months and longer than 59 months were also associated with a
significantly greater risk for the 3 adverse perinatal outcomes.
Conclusions: Interpregnancy intervals shorter than 18 months and longer than 59 months are significantly
associated with increased risk of adverse perinatal outcomes. These data suggest that spacing pregnancies
appropriately could help prevent such adverse perinatal outcomes.
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Interpregnancy interval and risk of preterm birth and neonatal death: retrospective cohort study (British
Medical Journal, 2003)
Objective: To determine whether a short interval between pregnancies is an independent risk factor for
adverse obstetric outcome.
Design: Retrospective cohort study.
Setting: Scotland.
Subjects: 89 143 women having second births in 1992-8 who conceived within five years of their first birth.
Main outcome measures: Intrauterine growth restriction (birth weight less than the 5th centile for gestational
age), extremely preterm birth (24-32 weeks), moderately preterm birth (33-36 weeks), and perinatal death.
Results: Women whose subsequent interpregnancy interval was less than six months were more likely than
other women to have had a first birth complicated by intrauterine growth restriction (odds ratio 1.3, 95%
confidence interval 1.1 to 1.5), extremely preterm birth (4.1, 3.2 to 5.3), moderately preterm birth (1.5, 1.3 to
1.7), or perinatal death (24.4, 18.9 to 31.5). They were also shorter, less likely to be married, and more likely
to be aged less than 20 years at the time of the second birth, to smoke, and to live in an area of high
socioeconomic deprivation. When the outcome of the second birth was analysed in relation to the preceding
interpregnancy interval and the analysis confined to women whose first birth was a term live birth (n = 69
055), no significant association occurred (adjusted for age, marital status, height, socioeconomic deprivation,
smoking, previous birth weight vigesimal, and previous caesarean delivery) between interpregnancy interval
and intrauterine growth restriction or stillbirth. However, a short interpregnancy interval ( < 6 months) was an
independent risk factor for extremely preterm birth (adjusted odds ratio 2.2, 1.3 to 3.6), moderately preterm
birth (1.6, 1.3 to 2.0), and neonatal death unrelated to congenital abnormality (3.6, 1.2 to 10.7). The adjusted
attributable fractions for these associations were 6.1%, 3.9%, and 13.8%. The associations were very similar
when the analysis was confined to married non-smokers aged 25 and above.
Conclusions: A short interpregnancy interval is an independent risk factor for preterm delivery and neonatal
death in the second birth.
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Factor Increased # of Hamilton County Notes

likelihood Women impacted
of preterm annually
birth

Smoking <2X (OR 1.40- ~2,000 women

1.50)

Relationship of trimester-specific smoking patterns and risk of preterm birth (American Journal of Obstetrics
& Gynecology, 2016)
Background: In 2011, the US national rate of smoking early in pregnancy was 11.5%. Unfortunately, our home
state of Ohio had a rate twice as high at 23%. Smoking in pregnancy remains one of the most important
modifiable risk factors for pregnancy complications, specifically preterm birth.
Objective: The objective of the study was to quantify the preterm birth risk to various trimester-specific
smoking behaviors.
Study Design: The study was a population-based, retrospective cohort study of singleton non-anomalous live
births, using Ohio birth records 2006 to 2012. Preterm birth rates were compared between nonsmokers and
women who smoked in the preconception period only, those who quit smoking after the 1st and 2nd
trimesters, and those who smoked throughout pregnancy. Multivariate logistic regression quantified the risk
of smoking with cessation at various times in pregnancy and preterm birth risk, adjusted for maternal race,
education, age, Medicaid use, marital status, and parity. A stratified analysis was performed on the basis of
preterm birth subtype: spontaneous preterm birth versus indicated preterm birth. We also performed an
additional analysis stratifying for maternal race using the 2 largest categories of race (non-Hispanic white and
non-Hispanic black).
Results: Of the 913,757 birth records analyzed, nearly 25% of the women reported some smoking behavior on
the birth certificate data. Of smokers, less than half quit during pregnancy (38.8% vs 61.2% smoked
throughout pregnancy). Early quitters had a similar preterm birth rate compared with non-smokers. Women
who smoked through the 1st trimester only did not have a significant increase in their overall preterm birth
odds ratio <37 weeks; however, it did increase the odds of extreme preterm birth <28 weeks by 20% (adjusted
odds ratio, 1.20; 95% confidence interval [CI], 1.02, 1.40). Quitting late in pregnancy resulted in the highest
odds ratio increase: 70% for preterm birth <37 weeks (adjusted odds ratio 1.70; CI, 1.60, 1.80), even after
adjustment for the confounding influences. Quitting smoking early in pregnancy after the 1 st trimester did not
increase the overall risk of spontaneous or indicated preterm birth <37 weeks significantly. However, quitting
after the 1st trimester was associated with a significant increase in risk of extreme spontaneous preterm birth
<28 weeks, an effect not seen with indicated preterm birth <28 weeks. Delaying cessation until late in
pregnancy—after the 2nd trimester—was associated with the highest risk increases, 65% increased odds of
spontaneous and 78% increase in odds of indicated preterm births. The rate of preterm births to non-Hispanic
black mothers was increased in all categories over those of non-Hispanic white mothers. The relative influence
of smoking cessation in pregnancy was similar in black compared with white mothers. The effect modification
in the regression model was analyzed and revealed no significant interaction between race and smoking
patterns on preterm birth risk.
Conclusion: Smoking throughout pregnancy is associated with an increased risk of preterm birth. However,
quitting early in pregnancy negates this risk. Widespread programs aimed at smoking cessation early in
pregnancy could have a significant impact on reducing the rate of preterm birth nationally.
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Self-reported and laboratory evaluation of late pregnancy nicotine exposure and drugs of abuse (Journal of
Perinatology, 2016)
Objective: The objective of this study was to evaluate the prevalence of late pregnancy nicotine exposures,
including secondhand smoke exposures, and to evaluate the associated risk of exposure to drugs of abuse.
Study Design: The study was a retrospective single-center cohort analysis of more than 18 months. We
compared self-reported smoking status from vital birth records with mass spectrometry laboratory results of
maternal urine using a chi-square test. Logistic regression estimated adjusted odds for detection of drugs of
abuse based on nicotine detection.
Results: Compared with 8.6% self-reporting cigarette use, mass spectrometry detected high-level nicotine
exposures for 16.5% of 708 women (P<0.001) and an additional 7.5% with low-level exposures. We identified
an increased likelihood of exposure to drugs of abuse, presented as adjusted odds ratios, (95% confidence
interval (CI)), for both low-level (5.69, CI: 2.09 to 15.46) and high-level (13.93, CI: 7.06 to 27.49) nicotine
exposures.
Conclusion: Improved measurement tactics are critically needed to capture late pregnancy primary and
passive nicotine exposures from all potential sources.

Association of Reported Trimester-Specific Smoking Cessation and Fetal Growth Restriction (Obstetrics &
Gynecology, 2015)
Objective: To assess the association of reported smoking cessation at various time points during pregnancy
with fetal growth restriction.
Methods: This was a population-based retrospective cohort study of singleton nonanomalous live births using
Ohio birth certificates, 2006–2012. Outcomes of women who reported smoking only in the 3 months before
conception and women who reported smoking through the first, second, or third trimester were compared
with a referent group of nonsmokers. Multivariate logistic regression assessed the association between
smoking cessation at various times in pregnancy and fetal growth restriction less than the 10th and 5th
percentiles.
Results: Of 927,424 births analyzed, 75% of mothers did not smoke. Of smokers, 24% smoked preconception
only, 10% quit after the first trimester, 4% quit after the second trimester, and 59% smoked throughout
pregnancy. The rate of fetal growth restriction less than the 10th and 5th percentiles among nonsmokers was
8.1% and 3.6%, respectively. Although smoking only in the preconception period did not significantly increase
fetal growth restriction risk, smoking in any trimester did. The adjusted odds ratio (95% confidence interval)
for fetal growth restriction less than the 10th and 5th percentiles, respectively, of cessation after the first
trimester was 1.19 (1.13–1.24) and 1.25 (1.17–1.33) and 1.67 (1.57–1.78) and 1.83 (1.68, 1.99) for cessation
after the second trimester. Women who reported smoking throughout pregnancy had the highest risks of fetal
growth restriction, 2.26 (2.22–2.31) and 2.44 (2.37–2.51), after accounting for the influence of race, low
socioeconomic status, and medical comorbidities.
Conclusion: Smoking of any duration during pregnancy is associated with an increased risk of fetal growth
restriction with decreasing risk the earlier that cessation occurs. Smoking cessation programs should focus on
the benefit of quitting as early in pregnancy as possible.
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Smoking in pregnancy revisited: Findings from a large population-based study (American Journal of
Obstetrics & Gynecology, 2005)
Objective: The purpose of this study was to characterize the effect of smoking on the incidence of various
pregnancy complications.
Study design: A population-based retrospective analysis with a perinatal database of 170,254 singleton
pregnancies was performed. The rate of pregnancy complications was calculated in 4 strata of smokers:
Nonsmokers, 1 to 5 cigarettes per day, 6 to 10 cigarettes per day, and >10 cigarettes per day. Logistic
regression was used to calculate odds ratios as measures of an association of smoking with various pregnancy
complications after correction for confounding factors.
Results: The mean age of the study population was 29 ± 4.8 years. The odds ratio for preeclampsia was 0.64
(95% CI, 0.59-0.70), for intrauterine growth restriction was 2.4 (95% CI, 2.34-2.53), and for preterm delivery
was 1.2 (95% CI, 1.13-1.28).
Conclusion: Smoking decreased the incidence of preeclampsia in a dose-effect manner and was shown to
increase the rate of intrauterine growth restriction and preterm delivery.
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ABSTRACTS
LITERATURE – PRETERM BIRTH, MIXED EVIDENCE

There is mixed evidence that the following risk factors contribute to preterm birth.
• Father involvement
• Working conditions
• Social Support
• Unintended Pregnancy
• Unsafe or Unstable Housing
• Mom’s Age Greater than 35
• Mom’s Stress
This section includes abstracts of the literature reviewed for the risk factors above.

Click on the individual risk factors above to view the corresponding abstracts.
Click on the article titles to access full text in the following pages.
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Factor Increased # of Hamilton County Notes

likelihood of women impacted
preterm birth annually

Father involvement 3X for infant Unknown Very limited research available

death* ~6000 unmarried
births
(OR 3.41)

Assessing the Impact of Paternal Involvement on Racial/Ethnic Disparities in Infant Mortality Rates (Journal
of Community Health, 2011)
We sought to assess the contribution of paternal involvement to racial disparities in infant mortality. Using
vital records data from singleton births in Florida between 1998 and 2005, we generated odds ratios (OR), 95%
confidence intervals (CI), and preventative fractions to assess the association between paternal involvement
and infant mortality. Paternal involvement status was based on presence/absence of paternal first and/or last
name on the birth certificate. Disparities in infant mortality were observed between and within racial/ethnic
subpopulations. When compared to Hispanic (NH)-white women with involved fathers, NH-black women with
involved fathers had a twofold increased risk of infant mortality whereas infants born to black women with
absent fathers had a seven-fold increased risk of infant mortality. Elevated risks of infant mortality were also
observed for Hispanic infants with absent fathers (OR = 3.33. 95%CI = 2.66–4.17). About 65–75% of excess
mortality could be prevented with increased paternal involvement. Paternal absence widens the black-white
gap in infant mortality almost four-fold. Intervention programs to improve perinatal paternal involvement may
decrease the burden of absent father-associated infant mortality.

Paternal support and preterm birth, and the moderation of effects of chronic stress: a study in Los Angeles
County mothers (Archives of Women's Mental Health, 2010)
Maternal psychosocial stress is an important risk factor for preterm birth, but support interventions have
largely been unsuccessful. The objective of this study is to assess how support during pregnancy influences
preterm birth risk and possibly ameliorates the effects of chronic stress, life event stress, or pregnancy anxiety
in pregnant women. We examined 1,027 singleton preterm births and 1,282 full-term normal weight controls
from a population-based retrospective case–control study of Los Angeles County, California women giving
birth in 2003, a mostly Latina population (both US-born and immigrant). We used logistic regression to assess
whether support from the baby’s father during pregnancy influences birth outcomes and effects of chronic
stress, pregnancy anxiety, and life event stress. Adjusted odds of preterm birth decreased with better support
(OR 0.73 [95%CI 0.52, 1.01]). Chronic stress (OR 1.46 [95%CI 1.11, 1.92]), low confidence of a normal birth (OR
1.57 [95% CI 1.17, 2.12]), and fearing for the baby’s health (OR 1.67 [95%CI 1.30, 2.14]) increased preterm
birth risk, but life events showed no association. Our data also suggested that paternal support may modify
the effect of chronic stress on the risk of preterm birth, such that among mothers lacking support, those with
moderate-to-high stress were at increased odds of delivering preterm (OR 2.15 [95%CI 0.92, 5.03]), but
women with greater support had no increased risk with moderate-to-high chronic stress (OR 1.13 [95%CI 0.94,
1.35]). Paternal support may moderate the effects of chronic stress on the risk of preterm delivery
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The Effects of Father Involvement during Pregnancy on Receipt of Prenatal Care and Maternal Smoking
(Maternal & Child Health Journal, 2007)
Objectives: To examine whether women whose partners are involved in their pregnancy are more likely to
receive early prenatal care and reduce cigarette consumption over the course of the pregnancy. This study
also examines sociodemographic predictors of father involvement during pregnancy.
Methods: Data on 5,404 women and their partners from the first wave of the Early Childhood Longitudinal
Study-Birth Cohort (ECLS-B) were used to examine the association between father involvement during
pregnancy and maternal behaviors during pregnancy. Multivariate linear and logistic regression analyses were
used and data were weighted to account for the complex survey design of the ECLS-B.
Results: Women whose partners were involved in their pregnancy were 1.5 times more likely to receive
prenatal care in the first trimester and, among those who smoked at conception, to reduce their cigarette
consumption 36% more than women whose partners were not involved in the pregnancy (p = .09). Fathers
with less than a high school education were significantly less likely to be involved in their partner’s pregnancy,
while first-time fathers and fathers who reported wanting the pregnancy were significantly more likely to be
involved.
Conclusions: The positive benefits of father involvement often reported in the literature on child health and
development can be extended into the prenatal period. Father involvement is an important, but understudied,
predictor of maternal behaviors during the prenatal period, and improving father involvement may have
important consequences for the health of his partner, her pregnancy, and their child.
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Factor Increased # of Hamilton County Notes

likelihood of women impacted
preterm birth annually

Working conditions 2X Unknown “Working long hours and

(OR 2.38)** undertaking hard physical labor
under stressful conditions are
probably associated.” Other studies
find little impact.

Physical Exertion at Work and the Risk of Preterm Delivery and Small-for-Gestational-Age Birth (Obstetrics &
Gynecology, 2005)
Objective: To assess whether exposure to standing, lifting, night work, or long work hours during 3 periods of
pregnancy are associated with an increased risk of preterm or small-for-gestational-age birth.
Methods: The Pregnancy, Infection and Nutrition study is a prospective cohort with a nested case–control
component that was conducted through clinic and hospital settings in Central North Carolina. A total of 1,908
women pregnant with a singleton gestation were recruited during prenatal visits from January 1995 through
April 2000 and provided information during telephone and face-to-face interviews about physical exertion for
the 2 longest-held jobs during pregnancy.
Results: No significant elevations in preterm delivery were observed among women who lifted repeatedly or
stood at least 30 hours per week, with no changes in risk estimates over the course of pregnancy. A 50%
elevation in the risk of preterm delivery (relative risk 1.5, 95% confidence interval 1.0 –2.0; first trimester) was
observed among women who reported working at night (10:00 PM to 7:00 AM), whereas a 40% reduction in
risk was observed among women working at least 46 hours per week (relative risk 0.6, 95% confidence interval
0.4–0.9; first trimester), regardless of period of exposure. No elevations in small-for-gestational-age birth were
observed among women exposed to any of the 4 types of occupational exertion.
Conclusion: Physically demanding work does not seem to be associated with adverse pregnancy outcomes,
whereas working at night during pregnancy may increase the risk of preterm delivery. Studies to examine the
effect of shift work on uterine activity would help to clarify the possibility of a causal effect on preterm birth.
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Employment, working conditions, and preterm birth: results from the Europop case-control survey (Journal
of Epidemiology & Community Health, 2004)
Study objective: To analyse the relation between preterm birth and working conditions in Europe using
common measures of exposure and to test whether employment related risks varied by country of residence.
Design: A case-control study in which cases included all consecutive singleton preterm births and controls
included one of every ten singleton term births in each participating maternity unit. Data about working
conditions were obtained by interview from women after delivery.
Setting: Sixteen European countries.
Participants: The analysis included 5145 preterm and 7911 term births of which 2369 preterm and 4098 term
births were to women employed during pregnancy. Analyses of working conditions were carried out for
women working through at least the third month of pregnancy.
Main results: Employed women did not have an excess risk of preterm birth. Among working women, a
moderate excess risk was observed for women working more than 42 hours a week (OR = 1.33, CI = 1.1 to 1.6),
standing more than six hours a day (OR = 1.26, CI = 1.1 to 1.5), and for women with low job satisfaction (OR =
1.27, CI = 1.1 to 1.5). There were stronger links in countries with a lower overall level of perinatal health and a
common practice of long prenatal leaves.
Conclusion: These findings show that specific working conditions affect the risk of preterm birth. They also
suggest employment related risks could be mediated by the social and legislative context.
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Occupational fatigue and preterm premature rupture of membranes (American Journal of Obstetrics &
Gynecology, 2001)
Objective: The aim of this study was to prospectively determine the relationship between occupational fatigue
and spontaneous preterm delivery segregated into the etiologically distinct categories of spontaneous
preterm labor, preterm premature rupture of membranes, and indicated preterm delivery.
Study Design: A total of 2929 women with singleton pregnancies at 22 to 24 weeks’ gestation were enrolled in
a multicenter (10 sites) Preterm Prediction Study. Patients reported the number of hours worked per week
and answered specific questions designed to determine the following 5 sources of occupational fatigue
described by Mamelle et al: posture, work with industrial machines, physical exertion, mental stress, and
environmental stress. Fatigue was quantified (0-5 index) according to the number of these sources positively
reported. Simple and Mantel-Haenszel χ2 tests were used to test the univariate association and hypothesis of a
linear trend between sources of occupational fatigue and spontaneous preterm delivery. Covariables were
considered by multivariate logistic regression analysis. Women who did not work outside the home were
considered separately from those who worked but did not report any sources of occupational fatigue.
Results: Each source of occupational fatigue was independently associated with a significantly increased risk of
preterm premature rupture of membranes among nulliparous women but not among multiparous women.
The risk of preterm premature rupture of membranes increased (P = .002) with an increasing number of
sources of occupational fatigue—not working outside the home, 2.1%; working but not reporting fatigue,
3.7%; working with 1 source of fatigue, 3.2%; working with 2 sources of fatigue, 5.2%; working with 3 sources
of fatigue, 5.1%; and working with 4 or 5 sources of fatigue, 7.4%. There was also a significant relationship (P =
.01) between preterm premature rupture of membranes and an increasing number of hours worked per week
among nulliparous women. Neither spontaneous preterm labor nor indicated preterm delivery was
significantly associated with occupational fatigue among either nulliparous or multiparous women.
Conclusion: The occupational fatigue index of Mamelle et al discriminated a group of nulliparous women at
increased risk for preterm premature rupture of membranes. The relationship between preterm premature
rupture of membranes and occupational fatigue or hours worked may provide guidelines according to which
nulliparous women and their employers can be advised.
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Factor Increased # of Hamilton County Notes

likelihood of women impacted
preterm birth annually

Social Support 2X ~2200 women

(OR 1.90)*** (self-report from
PRAMS)

Perceived social support interacts with prenatal depression to predict birth outcomes (Journal of Behavioral
Medicine, 2013)
Prenatal depression has been linked to adverse reproductive outcomes including preterm labor and delivery,
and low birth weight. Social support also has been linked to birth outcomes, and may buffer infants from the
adverse impact of maternal depression. In this prospective study, 235 pregnant women completed
questionnaires about depression and social support. Clinical interviews were administered to assess for DSM-
IV axis I disorders. Following delivery, birth outcomes were obtained from medical records. Babies of
depressed mothers weighed less, were born earlier and had lower Apgar scores than babies of nondepressed
mothers. Depressed women had smaller social support networks and were less satisfied with support from
social networks. We found no direct associations between perceived social support and birth weight.
However, depressed women who rated their partners as less supportive had babies who were born earlier and
had lower Apgar scores than depressed mothers with higher perceived partner support. Women’s perception
of partner support appears to buffer infants of depressed mothers from potential adverse outcomes. These
results are notable in light of the low-risk nature of our sample and point to the need for continued depression
screening in pregnant women and a broader view of risk for adverse birth outcomes. The results also suggest a
possible means of intervention that may ultimately lead to reductions in adverse birth outcomes.

Maternal Social Support and Neighborhood Income Inequality as Predictors of Low Birth Weight and
Preterm Birth Outcome Disparities: Analysis of South Carolina Pregnancy Risk Assessment and Monitoring
System Survey, 2000–2003 (Maternal & Child Health Journal, 2010)
Effects of income inequality on health and other social systems have been a subject of considerable debate,
but only a few studies have used multilevel models to evaluate these relationships. The main objectives of the
study were to (1) Evaluate the relationships among neighborhood income inequality, social support and birth
outcomes (low birth weight, and preterm delivery) and (2) Assess variations in racial disparities in birth
outcomes across neighborhood contexts of income distribution and maternal social support. We evaluated
these relationships by using South Carolina Pregnancy Risk Assessment and Monitoring System (PRAMS)
survey for 2000–2003 geocoded to 2000 US Census data for South Carolina. Multilevel analysis was used to
simultaneously evaluate the association between income inequality (measured as Gini), maternal social
relationships and birth outcomes (low birth weight and preterm delivery). The results showed residence in
neighborhoods with medium levels of income inequality was independently associated with low birth weight
(OR: 2.00; 95% CI 1.14–3.26), but not preterm birth; low social support was an independent risk for low birth
weight or preterm births. The evidence suggests that non-Hispanic black mothers were at increased risks of
low birth weight or preterm birth primarily due to greater exposures of neighborhood deprivations associated
with low income and reduced social support and modified by unequal income distribution.
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Support during pregnancy for women at increased risk of low birthweight babies (Review) (Cochrane
Database of Systematic Reviews, 2010)
Background: Studies consistently show a relationship between social disadvantage and low birthweight. Many
countries have programs offering special assistance to women thought to be at risk for giving birth to a low
birthweight infant. These programs may include advice and counseling (about nutrition, rest, stress
management, alcohol, and recreational drug use), tangible assistance (e.g., transportation to clinic
appointments, household help), and emotional support. The programs may be delivered by multidisciplinary
teams of health professionals, specially trained lay workers, or combination of lay and professional workers.
Objectives: The primary objective was to assess effects of programs offering additional social support
compared with routine care, for pregnant women believed at high risk for giving birth to babies that are either
preterm or weigh less than 2500 gm, or both, at birth. Secondary objectives were to determine whether
effectiveness of support was mediated by timing of onset (early versus later in pregnancy) or type of provider
(healthcare professional or lay woman).
Search methods: We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (January 2010).
Selection criteria: Randomized trials of additional support during at-risk pregnancy by either a professional
(social worker, midwife, or nurse) or specially trained lay person, compared to routine care. We defined
additional support as some form of emotional support (e.g., counseling, reassurance, sympathetic listening)
and information or advice or both, either in home visits or during clinic appointments, and could include
tangible assistance (e.g., transportation to clinic appointments, assistance with care of other children at
home).
Data collection and analysis: Two review authors evaluated methodological quality. We performed double
data entry.
Main results: We included 17 trials (12,264 women). Programs offering additional social support for at-risk
pregnant women were not associated with improvements in any perinatal outcomes, but there was a
reduction in the likelihood of antenatal hospital admission (three trials; n = 737; RR 0.79, 95% CI 0.68 to 0.92)
and caesarean birth (nine trials; n = 4522; RR 0.87, 95% CI 0.78 to 0.97).
Authors’ conclusions: Pregnant women need the support of caring family members, friends, and health
professionals. While programs which offer additional support during pregnancy are unlikely to prevent the
pregnancy from resulting in a low birthweight or preterm baby, they may be helpful in reducing the likelihood
of antenatal hospital admission and caesarean birth.
Plain Language Summary: Support during pregnancy for women at increased risk of low birthweight babies.
Programs offering additional support during pregnancy were not effective in reducing number of babies born
too early and babies with low birthweights. Babies born to mothers in socially disadvantaged situations are
more likely to be small and so have health problems. Programs providing emotional support, practical
assistance, and advice have been offered in addition to usual care. The Review of 17 randomized controlled
trials, involving 12,264 women, found that women who received additional support during pregnancy were
less likely to be admitted to the hospital for pregnancy complications and to have a caesarean birth. However,
the additional support did not reduce the likelihood of giving birth too early or that the baby was smaller than
expected.
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Social Capital, Income Inequality, and Mortality (American Journal of Public Health, 1997)
Objectives: Recent studies have demonstrated that income inequality is related to mortality rates. It was
hypothesized, in this study, that income inequality is related to reduction in social cohesion and that
disinvestment in social capital is in turn associated with increased mortality.
Methods: In this cross-sectional ecologic study based on data from 39 states, social capital was measured by
weighted responses to two items from the General Social Survey: per capita density of membership in
voluntary groups in each state and level of social trust, as gauged by the proportion of residents in each state
who believed that people could be trusted. Age-standardized total and cause-specific mortality rates in 1990
were obtained for each state.
Results: Income inequality was strongly correlated with both per capita group membership (r = -.46) and lack
of social trust (r = .76). In turn, both social trust and group membership were associated with total mortality,
as well as rates of death from coronary heart disease, malignant neoplasms, and infant mortality.
Conclusions: These data support the notion that income inequality leads to increased mortality via
disinvestment in social capital.
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Factor Increased # of Hamilton County Notes

likelihood of women impacted
preterm birth annually

Unintended 2X ~4700 women Some studies find an impact, others

Pregnancy (OR 1.82)**** (self-report from find none.
PRAMS)

The Effects of Unintended Pregnancy on Infant, Child, and Parental Health: A Review of the Literature
(Studied in Family Planning, 2008)
This article provides a critical review of studies assessing the effects of unintended pregnancy on the health of
infants, children, and parents in developed and developing countries. A framework for determining and
measuring the pathways between unintended pregnancy and future health outcomes is outlined. The review
highlights persistent gaps in the literature, indicating a need for more studies in developing countries and for
further research to assess the impact of unintended pregnancy on parental health and long-term health
outcomes for children and families. The challenges in measuring and assessing these health impacts are also
discussed, highlighting avenues in which further research efforts could substantially bolster existing
knowledge.

Unintended pregnancy and preterm birth (Paediatric and Perinatal Epidemiology, 2000)
About one-third of all pregnancies that result in live births in the US are unintended. Despite the large number
of these births, little is known about the outcomes of unintended pregnancies. The purpose of the current
study was to evaluate the association between intendedness of pregnancy and preterm birth in a large
prospective cohort of women who reported for prenatal care. Pregnant, black, low-income women were
enrolled into this study at four hospital-based prenatal care clinics and one off-site hospital-affiliated prenatal
clinic in Baltimore City. A self-administered questionnaire to assess demographic and psychosocial data was
completed by each woman in the cohort at the time of enrolment in the study. The questionnaire contained
an item to measure intendedness of the pregnancy. A total of 922 women comprised the final sample for
analysis. For the analyses, intendedness was dichotomised as: intended (wanted now or sooner) vs.
unintended (mistimed, unwanted or unsure). Overall, 13.7% of all births to women in the sample were
preterm. In a logistic regression model, after controlling for potential confounding by clinical and behavioural
predictors of preterm delivery, unintended pregnancy was significantly associated with preterm delivery
(adjusted RR = 1.82, 95% confidence interval [1.08,3.08], P = 0.026). In this study of a cohort of urban, clinic-
attending, low-income, pregnant black women, unintended pregnancy had a statistically significant
association with preterm birth. After adjustment for behavioural and clinical risks, women with unintended
pregnancies had almost twice the risk of a preterm delivery as women with intended pregnancies.
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Factor Increased # of Hamilton County Notes

likelihood of women impacted
preterm birth annually

Unsafe or Unstable <2X Unknown

Housing (OR 1.46) ~2400 report fair or
poor housing

From Redlined to Evicted: Understanding The Relationship Between Housing & Maternal Health (2017)
Presentation for the “Addressing Housing Instability, Inequity, and Inadequacy” panel at CityMatch’s 2017
Annual Conference.

Housing influences among sleep-related infant injury deaths in the USA (Health Promotion International,
2016)
This article examines the role of housing conditions in sleep-related infant injury death, a leading cause of
infant mortality in the USA. The use of an unsafe sleep surface is a major risk factor for sleep-related infant
injury. This exploratory study examined contextual circumstances, specifically those related to the physical
environment, which may contribute to caregivers’ decisions to place an infant on an unsafe sleep surface. It
employed a retrospective review of 255 sleep-related infant injury death cases in a large urban area from 2004
to 2010 where an infant was found sleeping on an unsafe sleep surface, including 122 cases where a crib or
bassinet was identified in the home. Quantitative findings indicated no differences in demographic or risk
characteristics between infants with cribs or bassinets and those without them. Qualitative findings suggested
the lack of crib or bassinet use may be related to environmental factors influenced by poverty, specifically
crowded living space, room temperature and vermin infestation. This study suggests that infants may be at
risk of sleep-related injury deaths even when a crib or bassinet is present in the home and supports the
consideration of housing conditions in health promotion efforts to reduce infant mortality. Understanding
environmental factors that may contribute to infants sleeping on an unsafe surface can help maternal child
health and public health professionals develop more appropriate interventions that address deleterious living
conditions.
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Housing Transitions and Low Birth Weight Among Low-Income Women: Longitudinal Study of the Perinatal
Consequences of Changing Public Housing Policy (American Journal of Public Health, 2012)
Objectives: We assessed the longitudinal association between housing transitions and pregnancy outcomes in
a sample of public housing residents.
Methods: A cohort of 2670 Black women residing in Atlanta, Georgia, housing projects with 1 birth occurring
between 1994 and 2007 was created from maternally linked longitudinal birth files and followed for
subsequent births. Traditional regression and marginal structural models adjusting for time-varying
confounding estimated the risk of preterm low birth weight (LBW) or small for gestational age LBW by
maternal housing transition patterns.
Results: Women moving from public to private housing as a result of housing project demolition were at
elevated risk for preterm LBW (risk ratio = 1.74; 95% confidence interval = 1.00–3.04) compared with women
not affected by project demolition. Other non–policy-related housing transition patterns were not associated
with pregnancy outcomes.
Conclusions: Further longitudinal study of housing transitions among public housing residents is needed to
better understand the relationship between housing, neighborhoods, housing policy, and perinatal outcomes.

Adverse perinatal outcomes associated with homelessness and substance use in pregnancy (Canadian
Medical Association Journal, 2005)
Background: Women who are homeless during pregnancy may be exposed to poor nutrition, violence and
substance use, yet the health status of their newborn infants has not been systematically evaluated. We
undertook a study to provide preliminary estimates of the risk of adverse perinatal outcomes among Canadian
women who are homeless or marginally housed during pregnancy, and the effect of concomitant substance
use.
Methods: We conducted a retrospective cohort study at a single downtown hospital from October 2002 to
December 2004, involving women who, during pregnancy, were homeless or underhoused (n = 80), substance
users (n = 59) or neither (n = 3756). We noted neonatal measures such as birth weight and gestational age; the
main study outcomes were preterm birth before 37 weeks’ gestation, birth weight less than 2000 g and small
for gestational age at birth.
Results: Homelessness or inadequate housing was associated with an odds ratio (adjusted for maternal age,
gravidity and being a current smoker of tobacco) of 2.9 (95% confidence interval [CI] 1.4–6.1) for preterm
delivery, 6.9 (95% CI 2.4– 20.0) for infant birth weight under 2000 g and 3.3 (95% CI 1.1–10.3) for delivery of a
newborn small for gestational age. Adjusted odds ratios for substance use during pregnancy were similar. In
the combined presence of an underhoused or homeless state and maternal substance use, the adjusted risk
estimates were 5.9 (95% CI 1.9–18.5), 16.6 (95% CI 3.5–79.3) and 5.6 (95% CI 1.1–28.7), respectively.
Interpretation: Homelessness and maternal substance use may reduce neonatal well-being through
prematurity and low birth weight.
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Severity of Homelessness and Adverse Birth Outcomes (Health Psychology, 2000)

Predictors and the prevalence of adverse birth outcomes among 237 homeless women interviewed at 78
shelters and meal programs in Los Angeles in 1997 were assessed. It was hypothesized that they would report
worse outcomes than national norms, that African Americans would report the worst outcomes because of
their greater risk in the general population, and that homelessness severity would independently predict
poorer outcomes beyond its association with other adverse conditions. Other predictors included
reproductive history, behavioral and health-related variables, psychological trauma and distress, ethnicity, and
income. African Americans and Hispanics reported worse outcomes than are found nationally, and African
Americans reported the worst outcomes. In a predictive structural equation model, severity of homelessness
significantly predicted low birth weight and preterm births beyond its relationship with prenatal care and
other risk factors.
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Factor Increased # of Hamilton County Notes

likelihood of women impacted
preterm birth annually

Mom’s Age Greater <2X ~1100 women

than 35 (OR 1.38)

Effects of Maternal Age and Age-Specific Preterm Birth Rates on Overall Preterm Birth Rates — United
States, 2007 and 2014 (Morbidity and Mortality Weekly Report, 2016)
Reductions in births to teens and preterm birth rates are two recent public health successes in the United
States (1,2). From 2007 to 2014, the birth rate for females aged 15–19 years declined 42%, from 41.5 to 24.2
per 1,000 females. The preterm birth rate decreased 8.4%, from 10.41% to 9.54% of live births (1). Rates of
preterm births vary by maternal age, being higher among the youngest and oldest mothers. It is unknown how
changes in the maternal age distribution in the United States have affected preterm birth rates. CDC used
birth data to assess the relative contributions of changes in the maternal age distribution and in age-specific
preterm birth rates to the overall decrease in preterm birth rates. The preterm birth rate declined in all age
groups. The effects of age distribution changes on the preterm birth rate decrease were different in younger
and older mothers. The decrease in the proportion of births to mothers aged ≤19 and 20–24 years and
reductions in age-specific preterm rates in all age groups contributed to the overall decline in the preterm
birth rate. The increase in births to mothers aged ≥30 years had no effect on the overall preterm birth rate
decrease. The decline in preterm births from 2007 to 2014 is related, in part, to teen pregnancy prevention
and the changing maternal age distribution. Effective public health strategies for further reducing preterm
birth rates need to be tailored to different age groups.
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Factor Increased # of Hamilton County Notes

likelihood of women impacted
preterm birth annually

Mom’s Stress <2X Unknown (depends on Mixed results as to whether chronic

(OR 1.16)***** specific definition of or acute stress matters more.
stress)

Maternal Adverse Childhood Experience and Infant Health: Biomedical and Psychosocial Risks as
Intermediary Mechanisms (Journal of Pediatrics, 2017)
Objective: To assess the mechanisms accounting for the transfer of risk from one generation to the next,
especially as they relate to maternal adverse childhood experiences and infant physical and emotional health
outcomes.
Study design: Participants were 501 community mother-infant dyads recruited shortly after the birth and
followed up at 18 months. Mothers retrospectively reported on their adverse childhood experiences. The
main outcome measures were parent-reported infant physical health and emotional problems. Potential
mechanisms of intergenerational transmission included cumulative biomedical risk (eg, prenatal and perinatal
complications) and postnatal psychosocial risk (eg, maternal depression, single parenthood, marital conflict).
Results: Four or more adverse childhood experiences were related to a 2- and 5-fold increased risk of
experiencing any biomedical or psychosocial risk, respectively. There was a linear association between number
of adverse childhood experiences and extent of biomedical and psychosocial risk. Path analysis revealed that
the association between maternal adverse childhood experiences and infant physical health operated
specifically through cumulative biomedical risk, while the relationship between adverse childhood experiences
and infant emotional health operated specifically through cumulative psychosocial risk. This pattern was not
explained by maternal childhood disadvantage or current neighborhood poverty.
Conclusions: Maternal adverse childhood experiences confer vulnerability to prenatal, perinatal, and postnatal
psychosocial health. The association between adverse childhood experiences and offspring physical and
emotional health operates through discrete intermediary mechanisms.

The Effect of Maternal Stress on Birth Outcomes: Exploiting a Natural Experiment (Demography, 2011)
A growing body of research highlights that in utero conditions are consequential for individual outcomes
throughout the life cycle, but research assessing causal processes is scarce. This article examines the effect of
one such condition—prenatal maternal stress—on birth weight, an early outcome shown to affect cognitive,
educational, and socioeconomic attainment later in life. Exploiting a major earthquake as a source of acute
stress and using a difference-in-difference methodology, I find that maternal exposure to stress results in a
significant decline in birth weight and an increase in the proportion of low birth weight. This effect is focused
on the first trimester of gestation, and it is mediated by reduced gestational age rather than by factors
affecting the intrauterine growth of term infants. The findings highlight the relevance of understanding the
early emergence of unequal outcomes and of investing in maternal well-being since the onset of pregnancy.
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Maternal Stress and Preterm Birth (American Journal of Epidemiology, 2003)

This study examined a comprehensive array of psychosocial factors, including life events, social support,
depression, pregnancy-related anxiety, perceived discrimination, and neighborhood safety in relation to
preterm birth (<37 weeks) in a prospective cohort study of 1,962 pregnant women in central North Carolina
between 1996 and 2000, in which 12% delivered preterm. There was an increased risk of preterm birth among
women with high counts of pregnancy-related anxiety (risk ratio (RR) = 2.1, 95% confidence interval (CI): 1.5,
3.0), with life events to which the respondent assigned a negative impact weight (RR = 1.8, 95% CI: 1.2, 2.7),
and with a perception of racial discrimination (RR = 1.4, 95% CI: 1.0, 2.0). Different levels of social support or
depression were not associated with preterm birth. Preterm birth initiated by labor or ruptured membranes
was associated with pregnancy-related anxiety among women assigning a high level of negative impact
weights (RR = 3.0, 95% CI: 1.7, 5.3). The association between high levels of pregnancy-related anxiety and
preterm birth was reduced when restricted to women without medical comorbidities, but the association was
not eliminated. The prospective collection of multiple psychosocial measures on a large population of women
indicates that a subset of these factors is associated with preterm birth.

The preterm prediction study: Maternal stress is associated with spontaneous preterm birth at less than
thirty-five weeks' gestation (American Journal of Obstetrics & Gynecology, 1996)
Objective: Our purpose was to determine whether various measures of poor psychosocial status in pregnancy
are associated with spontaneous preterm birth, fetal growth restriction, or low birth weight.
Study Design: Anxiety, stress, self-esteem, mastery, and depression were assessed at 25 to 29 weeks in 2593
gravid women by use of a 28-item Likert scale. Scores for each psychosocial subscale were determined, and an
overall psychosocial score was calculated. Scores were divided into quartiles, and the lowest quartile scores
were used to define poor psychosocial status. The percent spontaneous preterm birth, low birth weight, and
fetal growth restriction in women with low and high psychosocial scores were compared. Logistic regression
analyses provided the odds ratios and 95% confidence intervals.
Results: Analyses revealed that stress was significantly associated with spontaneous preterm birth and with
low birth weight with odds ratios of 1.16, p = 0.003, and 1.08, p = 0.02, respectively, for each point on the
scale. A low score on the combined scale or on any subscale other than stress did not predict spontaneous
preterm birth, fetal growth restriction, or low birth weight. After multivariate adjustment was performed for
psychosocial status, substance use, and demographic traits, black race was the only variable significantly
associated with spontaneous preterm birth, fetal growth restriction, and low birth weight; stress and low
education were associated with spontaneous preterm birth and low birth weight.
Conclusion: Stress was associated with spontaneous preterm birth and low birth weight even after adjustment
for maternal demographic and behavioral characteristics. Black race continues to be a significant predictor of
spontaneous preterm birth, fetal growth restriction, and low birth weight even after adjustment for stress,
substance use, and other demographic factors.
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ABSTRACTS
LITERATURE – SOCIAL DETERMINANTS, ROLE IN PERTERM BIRTH

The following abstracts are from articles that discuss the role of social determinants in preterm birth.

Click on the article titles to access full text in the following pages.
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A Communicative Model of Mothers’ Lifestyles During Pregnancy with Low Birth Weight Based on Social
Determinants of Health: A Path Analysis (Oman Medical Journal, 2017)
Objectives: Low birth weight (LBW) is one of the major health problems worldwide. It is important to identify
the factors that play a role in the incidence of this adverse pregnancy outcome. This study aimed to develop a
tool to measure mothers’ lifestyles during pregnancy with a view to the effects of social determinants on
health and develop a correlation model of mothers’ lifestyles with LBW.
Methods: This study was conducted using methodological and case-control designs in four stages by selecting
750 mothers with infants weighing less than 4000 g using multistage sampling. The questionnaire contained
160 items. Face, content, criterion, and construct validity were used to study the psychometrics of the
instrument.
Results: After psychometrics, 132 items were approved in six domains. Test results indicated the utility and
the high fitness of the model and reasonable relationships adjusted for variables based on conceptual models.
Based on the correlation model of lifestyle, occupation (-0.263) and social relationships (0.248) had the
greatest overall effect on birth weight.
Conclusions: The review of lifestyle dimensions showed that all of the dimensions directly, indirectly, or both
affected birth weight. Thus, given the importance and the role of lifestyle as a determinant affecting birth
weight, attention, and training interventions are important to promote healthy lifestyles.

Living in stressful neighbourhoods during pregnancy: an observational study of crime rates and birth
outcomes (European Journal of Public Health, 2017)
Background: Patterns of adverse birth outcomes vary spatially and there is evidence that this may relate to
features of the physical environment such as air pollution. However, other social characteristics of the
environment such as levels of crime are relatively understudied. This study examines the association between
crime rates and birth weight and prematurity.
Methods: Maternity inpatient data recorded at birth, including residential postcode, was linked to a
representative 5% sample of Scottish Census data and small area crime rates from Scottish Police forces.
Coefficients associated with crime were reported from crude and confounder adjusted models predicting low
birth weight (< 2500 g), mean birthweight, small for gestational age and prematurity for all singleton live
births.
Results: Total crime rates were associated with strong and significant reductions in mean birth weight and
increases in the risks of both a small for gestational age baby and premature birth. These effects, with the
exception of prematurity, were robust to adjustment for individual characteristics including smoking, ethnicity
and other socio-economic variables as well as area based confounders including air pollution. Mean birth
weight was robust to additional adjustment for neighbourhood income deprivation.
Conclusion: The level of crime in a mother’s area of residence, which may be a proxy for the degree of threat
felt and therefore stress experienced, appears to be an important determinant of the risk of adverse birth
outcomes.
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The role of social determinants in explaining racial/ethnic disparities in perinatal outcomes (Pediatric
Research, 2016)
In the United States, there continue to be significant racial/ethnic disparities in preterm birth (PTB) rates,
infant mortality, and fetal mortality rates. One potential mediator of these disparities is social determinants of
health, including individual socioeconomic factors; community factors such as crime, poverty, housing, and the
racial/ethnic makeup of the community; and the physical environment. Previous work has identified
statistically significant associations between each of these factors and adverse pregnancy outcomes. However,
there are recent studies that provide new, innovative insights into this subject, including adding social
determinant data to population-based datasets; exploring multiple constructs in their analysis; and examining
environmental factors. The objective of this review will be to examine this recent research on the association
of each of these sets of social determinants on racial/ethnic disparities PTB, infant mortality, and fetal
mortality to highlight potential areas for targeted intervention to reduce these differences.

Risk Prediction for Adverse Pregnancy Outcomes in a Medicaid Population (Journal of Women's Health,
2015)
Background: Despite prior efforts to develop pregnancy risk prediction models, there remains a lack of
evidence to guide implementation in clinical practice. The current aim was to develop and validate a risk tool
grounded in social determinants theory for use among at-risk Medicaid patients.
Methods: This was a retrospective cohort study of 409 women across 17 Cincinnati health centers between
September 2013 and April 2014. The primary outcomes included preterm birth, low birth weight, intrauterine
fetal demise, and neonatal death. After random allocation into derivation and validation samples, a
multivariable model was developed, and a risk scoring system was assessed and validated using area under
the receiver operating characteristic curve (AUROC) values.
Results: The derived multivariable model (n = 263) included: prior preterm birth, interpregnancy interval, late
prenatal care, comorbid conditions, history of childhood abuse, substance use, tobacco use, body mass index,
race, twin gestation, and short cervical length. Using a weighted risk score, each additional point was
associated with an odds ratio of 1.57 for adverse outcomes, p < 0.001, AUROC= 0.79. In the validation sample
(n = 146), each additional point conferred an odds ratio of 1.20, p = 0.03, AUROC= 0.63. Using a cutoff of 20%
probability for the outcome, sensitivity was 29%, with specificity 82%. Positive and negative predictive values
were 22% and 85%, respectively.
Conclusions: Risk scoring based on social determinants can discriminate pregnancy risk within a Medicaid
population; however, performance is modest and consistent with prior prediction models. Future research is
needed to evaluate whether implementation of risk scoring in Medicaid prenatal care programs improves
clinical outcomes.
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The Social Determinants of Infant Mortality and Birth Outcomes in Western Developed Nations: A Cross-
Country Systematic Review (International Journal of Environmental Research and Public Health, 2013)
Infant mortality (IM) and birth outcomes, key population health indicators, have lifelong implications for
individuals, and are unequally distributed globally. Even among western industrialized nations, striking cross-
country and within-country patterns are evident. We sought to better understand these variations across and
within the United States of America (USA) and Western Europe (WE), by conceptualizing a social determinants
of IM/birth outcomes framework, and systematically reviewing the empirical literature on hypothesized social
determinants (e.g., social policies, neighbourhood deprivation, individual socioeconomic status (SES)) and
intermediary determinants (e.g., health behaviours). To date, the evidence suggests that income inequality
and social policies (e.g., maternal leave policies) may help to explain cross-country variations in IM/birth
outcomes. Within countries, the evidence also supports neighbourhood SES (USA, WE) and income inequality
(USA) as social determinants. By contrast, within-country social cohesion/social capital has been
underexplored. At the individual level, mixed associations have been found between individual SES,
race/ethnicity, and selected intermediary factors (e.g., psychosocial factors) with IM/birth outcomes.
Meanwhile, this review identifies several methodological gaps, including the underuse of prospective designs
and the presence of residual confounding in a number of studies. Ultimately, addressing such gaps including
through novel approaches to strengthen causal inference and implementing both health and non-health
policies may reduce inequities in IM/birth outcomes across the western developed world.
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ABSTRACTS
LITERATURE – PRETERM BIRTH, GENERAL

The following abstracts are from articles that provide a general overview on preterm birth and its risk factors.

Click on the article titles to access full text in the following pages.
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Predicting preterm birth among participants of North Carolina’s Pregnancy Medical Home Program
(Maternal & Child Health Journal, 2015)
Objective: To determine which combination of risk factors from Community Care of North Carolina’s (CCNC)
Pregnancy Medical Home (PMH) risk screening form was most predictive of preterm birth (PTB) by parity and
race/ethnicity.
Methods: This retrospective cohort included pregnant Medicaid patients screened by the PMH program
before 24 weeks gestation who delivered a live birth in North Carolina between September 2011-September
2012 (N=15,428). Data came from CCNC’s Case Management Information System, Medicaid claims, and birth
certificates. Logistic regression with backward stepwise elimination was used to arrive at the final models. To
internally validate the predictive model, we used bootstrapping techniques.
Results: The prevalence of PTB was 11%. Multifetal gestation, a previous PTB, cervical insufficiency, diabetes,
renal disease, and hypertension were the strongest risk factors with odds ratios ranging from 2.34 to 10.78.
Non-Hispanic black race, underweight, smoking during pregnancy, asthma, other chronic conditions,
nulliparity, and a history of a low birth weight infant or fetal death/second trimester loss were additional
predictors in the final predictive model. About half of the risk factors prioritized by the PMH program
remained in our final model (ROC=0.66). The odds of PTB associated with food insecurity and obesity differed
by parity. The influence of unsafe or unstable housing and short interpregnancy interval on PTB differed by
race/ethnicity.
Conclusions: Evaluation of the PMH risk screen provides insight to ensure women at highest risk are
prioritized for care management. Using multiple data sources, salient risk factors for PTB were identified,
allowing for better-targeted approaches for PTB prevention.

A Case-Control Study of Preterm Delivery Risk Factors According to Clinical Subtypes and Severity (The
Journal of Obstetrics & Gynaecology Research, 2010)
Aims: To examine risk factors of preterm delivery (PTD) among Thai women.
Methods: Our case-control study included 467 term controls and 467 PTD cases. PTD was studied in aggregate
and in subgroups (i.e., spontaneous preterm labor and delivery [SPTD], preterm premature rupture of
membrane [PPROM], medically indicated preterm delivery [MIPTD], moderate preterm delivery [32–36
weeks], and very preterm delivery [<32 weeks]). We used multivariable logistic regression procedures to
estimate odds ratio (OR) and 95% confidence intervals (CI) of potential PTD risk factors.
Results: Advanced maternal age (≥35 years) was associated with a 2.27-fold increased PTD risk overall (95%CI:
1.40, 3.68); and with a 3.79-fold increased risk of MIPTD (95%CI: 1.89, 7.59). Young maternal age (<20 years)
was associated with a 2.07-fold increased risk of SPTD (95%CI: 1.19, 3.61). Prior history of PTD was associated
with a 3.64-fold increased PTD risk overall (95%CI: 1.87, 7.09), and with a 5.69-fold increased risk of MIPTD
(95%CI: 2.44, 13.24). No prenatal care was associated with all PTD subtypes. Lean women (BMI<18.5 kg/m2),
compared with normal weight women (18.5–24.9 kg/m2), had a 1.70-fold increased risk of PTD (95%CI: 1.21,
2.39). Risk of SPTD (OR=2.16, 95%CI: 1.44, 3.24) and very PTD (OR=2.45, 95%CI: 1.35, 4.45) were also elevated
in lean women.
Conclusions: Maternal age, pre-pregnancy body mass index, prior history of PTD and no utilization of prenatal
care were covariates identified in this study as risk factors for PTD. Our findings also suggest heterogeneity in
risk factors for clinical subtypes of PTD.
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Predictive value of various risk factors for preterm labor (The Journal of Obstetrics & Gynaecology of India,
2010)
Objective(s): To evaluate the predictive value of risk factors for spontaneous preterm labor.
Method(s): This prospective study was conducted on 390 pregnant women, of which 290 in preterm labor
were taken as the study group and 100 in term labor were taken as controls. Risk factors were studied and
various risk factors were identified. Statistical analysis was done by logistic regression analysis using SPSS
software.
Result(s): Presence of factors like chorioamnionitis, bacterial vaginosis, urinary tract infection, heavy work,
prior preterm labor, medical disorders and placental abnormalities were significantly associated with preterm
labor.
Conclusion(s): Risk factors like previous preterm birth and placental abnormalities can not be modified hence
preventive efforts should be directed towards modifying working conditions during current pregnancy, good
antenatal care, and appropriate management of infections and medical disorders.
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ABSTRACTS
LITERATURE – SAFE SLEEP

The following abstracts are from articles on safe sleep and its impact on infant mortality.

Click on the article titles to access full text in the following pages
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New Frameworks for Understanding Sudden Unexpected Deaths in Infancy (SUDI) in Socially Vulnerable
Families (Journal of Pediatric Nursing, 2017)
Theoretical Principles: Sociological frameworks may enhance understanding of the complex and
multidimensional nature of disadvantage, which is prevalent among families who experience Sudden
Unexpected Death in Infancy (SUDI).
Phenomena Addressed: SUDI is the largest category of postneonatal death and largely associated with the
social determinants of health. The highly successful ‘Back to Sleep’ campaign has resulted in a more than 85%
decrease in SUDI. However, social inequalities have accompanied this decrease, and the burden of SUDI now
lies with the most disadvantaged and socially vulnerable families. A considerable body of research on the
phenomena of SUDI and disadvantage has been published over the last decade, demonstrating the widening
social gradient in SUDI, and the importance in recognising structural factors and the multifactorial nature of
disadvantage. Gaps in understanding of risk factors and scepticism about the received wisdom of health
professionals have emerged as central themes in understanding why socially vulnerable families may adopt
unsafe infant care practices. The direct impact of social disadvantage on infant care has also been recognised.
Research Linkages: The translation of epidemiological findings regarding SUDI risk into public health
recommendations for health professionals and families alike has to date focused on eliminating individual
level risk behaviours. Unfortunately, such a model largely ignores the broader social, cultural, and structural
contexts in which such behaviours occur. Translating the new knowledge offered by sociological frameworks
and the principles of behavioural economics into evidence based interventions may assist in the reduction of
SUDI mortality in our most socially vulnerable families.

Race, Ethnicity, and SIDS (Pediatrics, 2017)

In the United States, race and ethnicity predict different outcomes in known diseases. Race and ethnicity also
predict different outcomes in sudden infant death syndrome (SIDS) and sudden unexpected infant death
(SUID), categories of mortality that are arguably as yet undiscovered diseases. It is important to monitor
disparities affecting the health of children and to understand the impact of interventions aimed at them.
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SIDS and Other Sleep-Related Infant Deaths: Updated 2016 Recommendations for a Safe Infant Sleeping
Environment (Pediatrics, 2016)
Approximately 3500 infants die annually in the United States from sleep-related infant deaths, including
sudden infant death syndrome (SIDS; International Classification of Diseases, 10th Revision [ICD-10], R95), ill-
defined deaths (ICD-10 R99), and accidental suffocation and strangulation in bed (ICD-10 W75). After an initial
decrease in the 1990s, the overall death rate attributable to sleep-related infant deaths has not declined in
more recent years. Many of the modifiable and nonmodifiable risk factors for SIDS and other sleep-related
infant deaths are strikingly similar. The American Academy of Pediatrics recommends a safe sleep
environment that can reduce the risk of all sleep-related infant deaths. Recommendations for a safe sleep
environment include supine positioning, the use of a firm sleep surface, room-sharing without bed-sharing,
and the avoidance of soft bedding and overheating. Additional recommendations for SIDS reduction include
the avoidance of exposure to smoke, alcohol, and illicit drugs; breastfeeding; routine immunization; and use of
a pacifier. New evidence is presented for skin-to-skin care for newborn infants, use of bedside and in-bed
sleepers, sleeping on couches/armchairs and in sitting devices, and use of soft bedding after 4 months of age.
The recommendations and strength of evidence for each recommendation are included in this policy
statement. The rationale for these recommendations is discussed in detail in the accompanying technical
report

Relationship of Sudden Infant Death Syndrome to Maternal Smoking During and After Pregnancy (Pediatrics,
1992)
Sudden infant death syndrome (SIDS) is associated with maternal smoking during pregnancy. However, the
relationship between tobacco exposure during infancy and SIDS is unknown. The examination of infants whose
mothers smoked only after pregnancy will help determine the relationship between passive cigarette
exposure during infancy and SIDS risk. This case-control analysis used data on normal birth weight (> or = 2500
g) infants included in the National Maternal and Infant Health Survey, a nationally representative sample of
approximately 10,000 births and 6000 infant deaths. Infants were assigned to one of three exposure groups:
maternal smoking during both pregnancy and infancy (combined exposure), maternal smoking only during
infancy (passive exposure), and no maternal smoking. SIDS death was determined from death certificate
coding. Logistic regression was used to adjust for potentially confounding variables. Infants who died of SIDS
were more likely to be exposed to maternal cigarette smoke than were surviving infants. Among black infants
the odds ratio was 2.4 for passive exposure and 2.9 for combined exposure. Among white infants the odds
ratio was 2.2 for passive exposure and 4.1 for combined exposure. After adjustment for demographic risk
factors, the odds ratio for SIDS among normal birth weight infants was approximately 2 for passive exposure
and 3 for combined exposure for both races. These data suggest that both intrauterine and passive tobacco
exposure are associated with an increased risk of SIDS and are further inducement to encourage smoking
cessation among pregnant women and families with children.
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Human Reproduction, Vol.25, No.11 pp. 2894–2900, 2010

Advanced Access publication on July 19, 2010 doi:10.1093/humrep/deq177

ORIGINAL ARTICLE Reproductive epidemiology

Health disparities in risk for cervical

insufficiency
Emmanuel A. Anum 1, Haywood L. Brown 2, and Jerome F. Strauss III 1,*
1
Department of Obstetrics and Gynecology, Virginia Commonwealth University, Center on Health Disparities and Institute for Women’s
Health, MCV Campus, Sanger Hall, 1st Floor, Room 1-071, 1101 East Marshall Street, PO Box 980565, Richmond, VA 23298, USA
2
Department of Obstetrics and Gynecology, Duke University, Durham, NC 27710, USA

*Correspondence address. Tel: +1-804-828-9788; Fax: +1-804-828-7628; E-mail: jfstrauss@vcu.edu

Submitted on May 2, 2010; resubmitted on June 10, 2010; accepted on June 15, 2010

background: The purpose of the study was to examine racial/ethnic differences in cervical insufficiency risk.
methods: We used the US 2005 Natality data file. Analysis was limited to singleton births. The prevalence of cervical insufficiency was
examined by the maternal characteristic for each racial group. Unconditional logistic regression modeling was used to assess the association
between race and cervical insufficiency while controlling for confounders.
results: Cervical insufficiency risk for Black women was more than twice that for their White counterparts [odds ratio (OR) (95% con-
fidence interval (CI)) of 2.45 (2.22–2.71)]. Prior pregnancy termination showed a dose –response relationship with cervical insufficiency.
Compared with women with no history of prior pregnancy termination, primiparous women who have had one pregnancy termination
had an OR (95% CI) of 2.49 (2.23–2.77). The OR for two, three and four or more terminations were 4.66 (4.07–5.33), 8.07 (6.77–
9.61) and 12.36 (10.19–15.00), respectively. Other predictors of cervical insufficiency included previous preterm birth, parity, marital
status, renal disease, history of diabetes, polyhydramnios and anemia.
conclusions: There were significant racial/ethnic disparities with Black women having increased cervical insufficiency risk, indepen-
dent of other studied factors. Prior pregnancy termination is also a major risk factor for cervical insufficiency. The White/Black disparity
is evident in both primiparous and multiparous women.
Key words: cervical insufficiency / pregnancy termination / race/ethnicity

Surgical and medical treatments such as cervical biopsy, treatment

Introduction
Preterm birth accounts for 70% of all neonatal morbidity and mor-
tality (Mathews and MacDorman, 2008). One of the known risk
factors for preterm birth is cervical insufficiency. A cervix that
shows a painless dilation and shortening during the second trimester
of pregnancy with resultant recurrent pregnancy loss or delivery is
considered incompetent (Norman, 2007). Ultrasound assessment of
cervical length suggests that cervical sufficiency may be continuous
with incompetence occupying the extreme end of a continuum
(Warren and Silver, 2009).
About 27% of women with cervical insufficiency have been
reported to have first-degree female relatives who also have cervical
insufficiency (Warren et al., 2007). Cervical insufficiency has been
reported in pregnancies in women with the Ehlers–Danlos syndrome
(Leduc and Wasserstrum, 1992; De Vos et al., 1999) and Marfan syn-
drome (Paternoster et al., 1998; Rahman et al., 2003; Meijboom et al.,
2006; Tzialidou et al., 2007). Polymorphisms in the COL1A1 and
TGFB1 genes have been associated with cervical insufficiency.
for cervical cancer, routine dilation and curettage for diagnostic and
therapeutic purposes and termination of pregnancy, and trauma may
all result in structural damage to the cervix, which may lead to cervical
insufficiency. Forceful dilatation of the cervix performed during surgical
procedures, and termination of pregnancy has the potential to damage
the endocervix and result in cervical insufficiency, (Grunberger and
Riss, 1979) and subsequent preterm delivery. The length of the
cervix is an important risk factor in preterm delivery evaluation
(Petrovic et al., 2008) and the damage that repeated terminations
may cause to the cervix includes shortening of the cervix. A short cer-
vical length is a strong predictor of spontaneous preterm birth (Iams
et al., 1996; Goldenberg et al., 2008). In a study among women
with multiple prior-induced abortions, Visintine et al. (2008) reported
preterm birth incidence of 47% in women with a short cervix (cervical
length ,25 mm) compared with 14% among those without a short
cervix. Women who have had a prior spontaneous preterm delivery
at ,24 weeks have been found to have a higher incidence of cervical
shortening compared with those whose preterm delivery was at a

& The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which
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 RETURN TO TABLE OF CONTENTS
Disparities in risk for cervical insufficiency
later date (Szychowski et al., 2009). Cervical length has also been
found to be highly predictive of preterm birth in twin gestations (To
et al., 2006).
Although the association between cervical insufficiency and preterm
birth is well established, no study has at yet examined cervical insuffi-
ciency rates and risk by race. Blacks have a higher preterm birth rate
compared with Whites, and since having a preterm delivery is in itself
a risk factor for cervical insufficiency, this study examined cervical
insufficiency among primiparous women to determine if there are
ethnic and racial differences in cervical insufficiency risk.
Materials and Methods
We used the US 2005 Natality data file that includes data based on the
1989 Revision of the US Standard Certificate of Live Birth for deliveries
in 2004. The complete data set is available online at http://www.cdc.
gov/nchs/data_access/VitalStatsOnline.htm#Period_Linked. Data from
states that used the 2003 revised version of the Birth Certificate
[Pennsylvania, South Carolina, Tennessee, Texas, Washington, Florida,
Idaho, Kansas, Kentucky, New York (excluding New York City), Nebraska
and New Hampshire] could not be used since information on cervical
insufficiency, the outcome variable of interest, was only reported on the
unrevised 1989 version of the Certificate of Live Birth. Cervical insuffi-
ciency is considered to be present if the term ‘cervical incompetency’ is
checked on the birth certificate. The sample from New York City, the
District of Columbia and the 37 states that used the unrevised Certificate
represent 69% of all live births (ftp://ftp.cdc.gov/pub/Health_Statistics/
NCHS/Dataset_Documentation/DVS/natality/UserGuide2005.pdf). Our
analysis focused on primiparous women. All twins and any higher order
gestations were excluded from the analysis. Records with missing infor-
mation on cervical insufficiency were also excluded. The exposure variable
was mother’s race (given as White, Black, Asian/Pacific Islander or
American Indian/Alaskan native). Covariates included mother’s age and
education level, marital status, number of prior pregnancy terminations,
weight gain during pregnancy, maternal medical conditions (diabetes, preg-
nancy induced hypertension, anemia in pregnancy, hemoglobinopathy,
genital herpes, renal disease or hydramnios), tobacco and alcohol use
and adequacy of prenatal care. Mean ages and weight gain during preg-
nancy, and proportions of the various maternal characteristics were com-
puted for each racial group. The prevalence of cervical insufficiency
within each level of maternal characteristic was also assessed for each
racial group. ORs for the association between each covariate and cervical
insufficiency were computed. All clinically significant variables and any vari-
able showing a P-value of 0.25 or less from the crude analysis were con-
sidered candidates for the multivariate model. Unconditional logistic
regression modeling was used to assess the association between race and
cervical insufficiency while controlling for confounders. Contribution of
variables to the model was assessed by comparing the –2loglikelihood of
the models with and without the covariate. Model adequacy was assessed
using the Hosmer and Lemeshow Goodness-of-fit statistic. To check the
stability of our effect estimates from the primiparous-only model, we fitted
a second regression model that included women of all parity, controlling
also for number of live births now living, number of live births now dead,
and history of previous preterm birth. SAS 9.2 was used for statistical analysis.
Results
Of the 4 145 883 total live births recorded in 2004, 4 005 869 were
singleton births. The number of singleton births based on the 1989
Revision of the US Standard Certificate of live birth was 2 771 890.
2895
Of this number, 1 115 541 were deliveries to primiparous women.
A racial breakdown showed 852 296 (76.4%) were White, 166 966
(15.0%) were Black, 82 965 (7.4%) were Asian/Pacific Islanders and
the rest were American Indians/Alaskan natives (Table I). Their
mean ages ranged from 21.6 to 28.5 years. Approximately 0.23% of
records had missing information on cervical insufficiency. The pro-
portion of missing cervical insufficiency data among the different
racial groups was 0.22% for Whites, 0.27% for Blacks, 0.23% for
Asians and 0.66% for American Indians/Alaskan natives. Among
preterm and term deliveries, the missing proportions were 0.34 and
0.21%, respectively. While 60.5% of Whites gave their marital status
as ‘married’, among Blacks the proportion of married women was
21.9%. Asians/Pacific Islanders had the highest proportion of
married women (81.3%). All racial groups had some fraction of their
population with a history of at least one previous pregnancy termin-
ation. Blacks, however, had a significantly greater proportion of their
population with two or more pregnancy terminations. Anemia in preg-
nancy was most prevalent in American Indians/Alaskan natives (4.2%)
and least prevalent in Asians/Pacific Islanders (1.5%). Tobacco use
during pregnancy was more prevalent among Whites and American
Indians/Alaskan natives.
Approximately, one-half (49%) of all pregnancies among primipar-
ous women with cervical insufficiency ended in preterm delivery. Of
the preterm babies, 44% were delivered at 27 weeks of gestation or
less. Cervical insufficiency prevalence and 95% confidence interval
(95 % CI) for the different racial groups were 0.19% (0.19–0.20%)
for Whites, 0.53% (0.49–0.56%) for Blacks, 0.18% (0.15–0.21%)
for Asians/Pacific Islanders and 0.20% (0.14– 0.30%) for American
Indian/Alaskan natives (Table II). Cervical insufficiency prevalence
showed an increasing trend with increasing number of pregnancy ter-
minations. Whereas women with no history of pregnancy termination
had a cervical insufficiency prevalence of 0.15%, among those with
four or more terminations the prevalence was 3.15%. The cervical
insufficiency prevalence associated with one, two and three pregnancy
terminations were 0.46, 0.99 and 1.92%, respectively. High prevalence
rates were also recorded in women with diabetes, hemoglobinopa-
thies, renal disease and hydramnios. Women who had more than ade-
quate prenatal care (i.e. the ‘adequate plus’ group) also had a high
cervical insufficiency prevalence.
In the multivariate logistic regression that controlled for known cer-
vical insufficiency risk factors, the adjusted cervical insufficiency risk for
primiparous Black women was still more than twice that for their
White counterparts [odds ratio (OR) (95% CI) of 2.45 (2.22– 2.71)]
(Table III). American Indians/Alaskan natives also had an OR (95%
CI) of 1.62 (1.10–2.37) compared with Whites. The difference in cer-
vical insufficiency risk between Whites and Asians/Pacific Islanders
was not statistically significant. Pregnancy termination showed a
strong association with cervical insufficiency, with the risk increasing
as the number of previous pregnancy terminations increases. Com-
pared with women with no history of prior pregnancy termination, pri-
miparous women who have had one pregnancy termination had an
OR (95% CI) of 2.49 (2.23–2.77). The ORs for two, three and four
or more terminations were 4.66 (4.07–5.33), 8.07 (6.77–9.61) and
12.36 (10.19 –15.00), respectively. Other strong predictors of cervical
insufficiency were renal disease, history of diabetes, hydramnios and
anemia. Compared with women who received adequate prenatal
care, women who received adequate-plus care had an OR (95% CI)
 RETURN TO TABLE OF CONTENTS

2896 Anum et al.

Table I Maternal characteristics among primiparous women with singleton births by race, US 2005 Natality file.

Maternal characteristic White Black Asian/Pacific American Indian/Alaskan

Islander Native
.............................................................................................................................................................................................
N 852 296 166 966 82 965 13 314
Mother’s age* 25.4 (6.03) 22.8 (5.78) 28.5 (5.46) 21.6 (4.89)
Mother’s education
Some high school or less 159 359 (19.0%) 41 460 (25.2%) 6209 (7.6%) 4247 (32.3%)
High school graduate 237 711 (28.3%) 59 409 (36.2%) 15 479 (19.1%) 5194 (39.5%)
College 44 3770 (52.8%) 63 451 (38.6%) 59 537 (73.3%) 3717 (28.3%)
Married 516 009 (60.5%) 36 478 (21.9%) 67 457 (81.3%) 3459 (26.0%)
Previous pregnancy terminations
None 716 447 (84.1%) 132 332 (79.4%) 70 096 (84.5%) 11 363 (85.4%)
One 100 919 (11.9%) 23 221 (13.9%) 9414 (11.4%) 1469 (11.0%)
Two 24 626 (2.9%) 7512 (4.5%) 2505 (3.0%) 355 (2.7%)
Three 6594 (0.8%) 2371 (1.4%) 652 (0.8%) 82 (0.6%)
Four or more 3133 (0.4%) 1326 (0.8%) 268 (0.3%) 38 (0.3%)
Anemia 13 978 (1.6%) 5425 (3.3%) 1242 (1.5%) 554 (4.2%)
Diabetes 23 301 (2.7%) 4301 (2.6%) 4521 (5.5%) 589 (4.5%)
Genital herpes 8746 (1.0%) 2202 (1.3%) 363 (0.4%) 105 (0.8%)
Hemoglobinopathy 378 (0.04%) 567 (0.34%) 89 (0.11%) 5 (0.04%)
Renal disease 2900 (0.34%) 284 (0.17%) 142 (0.17%) 54 (0.41%)
Hydramnios/oligohydramnios 13 682 (1.6%) 3593 (2.2%) 1365 (1.7%) 265 (2.0%)
Pregnancy induced hypertension 44 324 (5.2%) 8832 (5.3%) 2008 (2.4%) 896 (6.8%)
Tobacco use 72 197 (10.5%) 6961 (4.5%) 832 (1.6%) 1822 (15.0%)
Alcohol use 4981 (0.7%) 598 (0.4%) 161 (0.3%) 224 (1.8%)
Adequacy of prenatal care
Inadequate 72 985 (8.8%) 24 018 (15.1%) 7405 (9.2%) 2555 (19.8%)
Intermediate 112 755 (13.6%) 23 445 (14.7%) 11 888 (14.8%) 2188 (16.9%)
Adequate 380 880 (45.9%) 60 907 (38.2%) 37 214 (46.3%) 4999 (38.7%)
Adequate plus 263 920 (31.8%) 51 099 (32.0%) 23 964 (29.8%) 3183 (24.6%)
Cervical insufficiency 1654 (0.19%) 876 (0.53%) 146 (0.18%) 27 (0.2%)
Weight gain during pregnancy* 33.3 (13.69) 31.0 (14.72) 31.2 (11.57) 33.5 (14.96)

*Mean (SD).
Cervical insufficiency is reported on the 1989 Revision of the US Certificate of Live Birth but not on the 2003 revised version. Thus, the analysis data set is only from States that report data
based on the 1989 Revision of the US Certificate of Live Birth.

of 2.91 (2.64– 3.22). This is not unexpected as women with cervical
insufficiency and other high-risk medical conditions are more likely
to begin prenatal care early and to have more prenatal visits. Their
prenatal care index would thus seem to be more than adequate.
Alcohol use, unmarried status and weight gain during pregnancy
each showed a reduction in incompetent cervix risk, but after fitting
the logistic regression model for multiparous women, alcohol use
was found not to be associated with an incompetent cervix
(Table III). Blacks still showed an OR (95% CI) of 2.18 (2.02– 2.36)
compared with Whites after adjustment for multiparous women.
This model also showed that the cervical insufficiency risk for
Whites did not differ from that of the other two racial groups.
Women with no college education also had a reduction in risk. Pro-
blems with small cell sizes may account for the unstable effect esti-
mates that alcohol use and American Indians/Alaskan natives
showed with the primiparous-only model. The model for multiparous
women showed previous preterm birth, number of live births living
and number of live births dead as strong predictors of cervical insuffi-
ciency. The strong positive trend associated with increasing number of
pregnancy terminations was still evident.
Discussion
Disparities in preterm delivery between Blacks and Whites in the USA
have existed for decades. Among the factors mentioned as contribut-
ing to these ethnic disparities are behavioral and socioeconomic
factors, maternal stress, racism and genetic factors. Studies on the
association of single gene defects with prematurity have provided evi-
dence that genetic factors may also contribute to preterm birth (Anum
et al., 2009). The present analysis highlights that race/ethnicity differ-
ences exist in the diagnosis of cervical insufficiency, a cause of preterm
delivery. The increased risk for cervical insufficiency among Black
 RETURN TO TABLE OF CONTENTS

Disparities in risk for cervical insufficiency 2897

Table II Prevalence of cervical insufficiency by Table II Continued

maternal characteristics among primiparous women
with singleton births, US 2005 Natality file. Variable Prevalence LL UL P-value
(%)
........................................................................................
Variable Prevalence LL UL P-value
Alcohol use 0.056
(%)
........................................................................................ No 0.26 0.25 0.27
Race ,0.0001 Yes 0.13 0.06 0.27
White 0.19 0.19 0.20 Adequacy of prenatal care ,0.0001
Black 0.53 0.49 0.56 Inadequate 0.14 0.12 0.17
Asian/Pacific Islander 0.18 0.15 0.21 Intermediate 0.12 0.11 0.14
American Indian/Alaskan 0.20 0.14 0.30 Adequate 0.14 0.13 0.15
native
Adequate plus 0.47 0.45 0.49
Previous pregnancy ,0.0001
terminations Confidence intervals were computed with the Clopper-Pearson (exact) method.
None 0.15 0.14 0.16 Two-sided P-values from Fisher’s exact test ( * ). Where 25% or more of cells had
expected counts less than five two-sided P-values from Fisher’s exact test was reported.
One 0.46 0.43 0.50
Two 0.99 0.89 1.10
Three 1.92 1.66 2.21
Four or more 3.15 2.68 3.69 women remained after controlling for other major risk factors, particu-
Mother’s education ,0.0001 larly prior pregnancy terminations.
Some high school or less 0.17 0.15 0.19 It should be noted that cervical insufficiency is often a diagnosis of
High school graduate 0.25 0.23 0.27 exclusion based upon a finding of advanced cervical dilatation or
history of pregnancy loss (Craigo, 1996). Moreover, the diagnosis of
College 0.27 0.26 0.28
cervical insufficiency was not made by standardized criteria across all
Marital status 0.003
obstetrical services. This represents a limitation of our study. It is poss-
Married 0.26 0.24 0.27
ible that women who delivered preterm would be more likely to
Not-married 0.23 0.21 0.24
check cervical insufficiency on the birth certificate as a complication
Anemia ,0.0001 compared with women who had cervical changes earlier in pregnancy,
No 0.24 0.23 0.25 but delivered at term. Women with a history of multiple prior preg-
Yes 0.39 0.31 0.48 nancy terminations who delivered preterm may also be more likely
Diabetes ,0.0001 to check cervical insufficiency as a complication. American Indians/
No 0.23 0.22 0.24 Alaskan natives had the highest proportion of missing cervical insuffi-
Yes 0.72 0.64 0.82 ciency data, but there were no significant differences in the proportion
Pregnancy induced 0.001 missing among the other racial groups. The diagnosis of cervical insuf-
hypertension ficiency can be challenging in women having their first delivery, and this
No 0.24 0.23 0.25 may result in cases of the condition not having been captured on the
Yes 0.31 0.26 0.36 birth certificate. There may also be under reporting of the number of
Genital Herpes ,0.0001 previous pregnancy terminations. These factors also represent limit-
ations of this study. It should also be noted that there is a high likeli-
No 0.24 0.23 0.25
hood of blank responses to some variables on the birth certificate,
Yes 0.47 0.36 0.62
which would lead to a list-wise deletion of such records in a logit
Hemoglobinopathy 0.015*
model. In this study, however, over 80% of all the records were uti-
No 0.24 0.23 0.25
lized in the multivariate logistic regression model.
Yes 0.67 0.27 1.38 Although findings on the association between prior pregnancy ter-
Renal disease 0.0006 mination and subsequent preterm delivery have been mixed (Pickering
No 0.24 0.23 0.25 and Forbes, 1985; Henriet and Kaminski, 2001; Moreau et al., 2005;
Yes 0.53 0.32 0.84 Raatikainen et al., 2006; Virk et al., 2007; Brown et al., 2008; Voigt
Hydramnios ,0.0001 et al., 2008, 2009; Freak-Poli et al., 2009), the observed ‘dose –
No 0.24 0.23 0.25 response relationship’ between number of pregnancy terminations
Yes 0.47 0.38 0.58 and preterm risk, as demonstrated in a recent meta-analysis by Shah
Tobacco use 0.328 and Zao (2009) provides strong evidence in favor of an association
between pregnancy termination and preterm birth. The strong associ-
No 0.26 0.25 0.27
ation between prior pregnancy termination and cervical insufficiency
Yes 0.24 0.21 0.28
irrespective of race/ethnicity was confirmed in our analysis. This
Continued relationship is presumed to be due to cervical trauma from the
 RETURN TO TABLE OF CONTENTS

2898 Anum et al.

Table III Crude and adjusted OR (95% CI) for cervical insufficiency by maternal characteristic among singleton live births,
US 2005 Natality file.

Variable Crude OR Adjusted OR* Adjusted OR**

.............................................................................................................................................................................................
Race (ref ¼ White)
Black 2.66 (2.43 –2.90) 2.45 (2.22– 2.71) 2.18 (2.02 –2.36)
Asian/Pacific Islander 1.10 (0.90 –1.34) 0.96 (0.79– 1.18) 0.97 (0.81 –1.16)
American Indian/Alaskan Native 1.16 (0.79 –1.70) 1.62 (1.10– 2.37) 1.02 (0.75 –1.38)
Pregnancy terminations (ref ¼ 0)
1 2.80 (2.53 –3.12) 2.49 (2.23– 2.77) 1.71 (1.57 –1.85)
2 6.03 (5.30 –6.87) 4.66 (4.07– 5.33) 2.86 (2.60 –3.16)
3 12.12 (10.26–14.32) 8.07 (6.77– 9.61) 3.55 (3.10 –4.06)
4+ 20.76 (17.31–24.91) 12.36 (10.19–15.00) 5.96 (5.24 –6.78)
Mother’s age 1.06 (1.06 –1.07) 1.03 (1.03– 1.04) 1.02 (1.02 –1.03)
Marital status: not married versus married 0.87 (0.80 –0.95) 0.89 (0.80– 0.99) 0.80 (0.73 –0.87)
Alcohol use 0.41 (0.18 –0.91) 0.37 (0.17– 0.84) 1.00 (0.69 –1.44)
History of diabetes 3.04 (2.63 –3.53) 1.69 (1.45– 1.98) 1.30 (1.15 –1.47)
Pregnancy-induced hypertension 1.19 (1.01 –1.41) 1.02 (0.86– 1.21) 0.90 (0.76 –1.06)
Anemia in pregnancy 1.55 (1.22 –1.96) 1.38 (1.08– 1.75) 1.25 (1.05 –1.49)
Genital herpes 1.88 (1.41 –2.51) 1.25 (0.93– 1.68) 1.57 (1.25 –1.96)
Renal disease 2.26 (1.40 –3.64) 2.21 (1.36– 3.59) 1.61 (1.10 –2.35)
Hydramnios/oligohydramnios 1.97 (1.58 –2.47) 1.48 (1.18– 1.86) 1.39 (1.13 –1.71)
Mother’s education level (ref ¼ college)
Some High school or less 0.58 (0.50 –0.66) 0.93 (0.79– 1.08) 0.66 (0.59 –0.74)
High school graduate 0.90 (0.82 –0.99) 1.05 (0.95– 1.17) 0.86 (0.80 –0.94)
Prenatal care adequacy (ref ¼ adequate)
Inadequate 1.04 (0.87 –1.26) 1.00 (0.82– 1.21) 0.70 (0.59 –0.82)
Intermediate 0.93 (0.78 –1.10) 0.88 (0.73– 1.05) 0.80 (0.70 –0.92)
Adequate plus 3.41 (3.09 –3.76) 2.91 (2.64– 3.22) 2.57 (2.38 –2.78)
Weight gain during pregnancy 0.97 (0.96 –0.97) 0.97 (0.97– 0.98) 0.99 (0.99 –0.99)
Previous preterm birth 8.16 (7.49 –8.89)
Live births now living (ref ¼ three or more)
0 4.18 (3.48 –5.02)
1 1.77 (1.60 –1.97)
2 1.38 (1.24 –1.55)
Live births now dead (ref ¼ 0)
One 4.90 (4.38 –5.48)
Two or more 5.69 (4.69 –6.90)

*Primiparous-only model; Hosmer and Lemeshow Goodness-of-fit test: P-value ¼ 0.18.

**Model with multiparous women. Cervical insufficiency is reported on the 1989 Revision of the US Certificate of Live Birth but not on the 2003 revised version. Thus, analysis data set is
only from States that report data based on the 1989 Revision of the US Certificate of Live Birth.

procedures. However, there are a number of relevant questions that
cannot be addressed in our study because information was not avail-
able, including whether the gestational age at which pregnancies were
terminated influences risk of cervical insufficiency, whether the
method and protocol for the procedures is a determinant of risk,
and whether the technical skill of the operator is a factor.
The association between risk for cervical insufficiency and diabetes,
and renal disease may reflect the biochemical sequela of glucose intol-
erance that influence tissue proteins. Post-translational modification of
tissue proteins (glycation) associated with hyperglycemia could
influence the structural integrity of the cervix. For example, collagen
glycation is known to occur in diabetes and is associated with diabetic
renal disease (Valcourt et al., 2007; Sell et al., 2010). Thus, there is
precedent for non-enzymatic post-translational protein modification
affecting extracellular matrix function. The relationship between
protein glycation and cervical insufficiency merits further evaluation.
Alternatively, the association between diabetes and cervical insuffi-
ciency could reflect the impact of body composition, assuming that
obesity is a factor contributing to diabetes and associated diabetic
nephropathy. African-American women have higher obesity rates in
 RETURN TO TABLE OF CONTENTS
Disparities in risk for cervical insufficiency
pregnancy than women of other races (Salihu et al., 2009). Since body
mass index was not available in the databases queried, we could not
test for associations between cervical insufficiency and obesity.
However, in a study of obese German women, cervical insufficiency
was less frequent in the obese population (Briese et al., 2010).
The risk differences for cervical insufficiency among ethnic groups
could be explained by environmental factors not assessed in our
study, such as infection leading to inflammatory changes in the
cervix. The incidence of sexually transmitted diseases and bacterial
vaginosis is higher in Blacks than Whites (Goldenberg et al., 1996;
Centers for Disease Control and Prevention, 2007) and this may be
one contributing factor to the increased risk among Blacks.
Genetic factors might also contribute to increased risk for cervical
insufficiency among Blacks. However, at present, there are no known
genetic variants that can explain this increased risk. It is of interest to
note that pelvic organ prolapse is less frequent in Black women than in
White women (Nygaard et al., 2008; Weiss et al., 2009; Whitcomb
et al., 2009; Sears et al., 2009; Chen et al., 2010). Thus, if variation in
genes encoding proteins involved in maintaining tissue integrity in the
pelvic floor and reproductive tract are involved, the disparate risks for
cervical insufficiency and pelvic floor dysfunction would predict that
the gene effects were highly specific to the uterine cervix.
In conclusion, our results strongly suggest that prior pregnancy ter-
mination is a major risk factor for cervical insufficiency. However, we
found significant racial/ethnic disparities with both primiparous and
multiparous Black women having an increased risk independent of
the influence of prior pregnancy terminations. This increased risk
among Blacks contributes to the racial/ethnic disparities in preterm
birth. The underlying cause(s) for the disparity in risk of cervical insuf-
ficiency are not known, but could include environmental factors
(reproductive tract infection/inflammation), biochemical changes
resulting from comorbid conditions (diabetes), and yet to be
defined genetic factors.
Funding
This work was supported by NIH P60 MD002256 and RO1
HD34612.
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Whitehead WE, Wu J, Brody DJ et al. Prevalence of symptomatic pelvic
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Original Article 787

Inadequate Prenatal Care Utilization and Risks

of Infant Mortality and Poor Birth Outcome:
A Retrospective Analysis of 28,729,765 U.S.
Deliveries over 8 Years
Sarah Partridge, M.D., B.Sc. 1 Jacques Balayla, M.D. 1 Christina A. Holcroft, Sc.D. 1
Haim A. Abenhaim, M.D., M.P.H. 1

1 Centre for Clinical Epidemiology and Community Studies, Jewish
General Hospital, Montreal, Quebec, Canada
Am J Perinatol 2012;29:787–794.
Address for correspondence and reprint requests Haim A. Abenhaim,
M.D., M.P.H., F.R.C.S.C., Department of Obstetrics and Gynecology,
Jewish General Hospital, McGill University, Pav H, 325, 5790 Cote-
Des-Neiges, Montréal, QC H3S 1Y9, Canada
(e-mail: haim.abenhaim@gmail.com).

Abstract Objective To evaluate the association between adequacy of prenatal care utilization

Downloaded by: University of Cincinnati. Copyrighted material.

and risk of fetal and neonatal mortality and adverse outcomes.
Methods We conducted a population-based cohort study using the Center for Disease
Control and Prevention’s Linked Birth-Infant Death and Fetal Death data on all deliveries
in the United States between 1995 and 2002. Inclusion criteria were singleton births

22 weeks of gestation with no known congenital malformation. Inadequate prenatal
care was defined according to the Adequacy of Prenatal Care Utilization Index, and its
effect on fetal and neonatal death was estimated using unconditional logistic regression
analysis adjusting for maternal age, race, education, and other confounding variables.
Results During our 8-year study period, 32,206,417 births occurred, 28,729,765
(89.2%) of which met inclusion criteria. Inadequate prenatal care utilization occurred
in 11.2% of expectant mothers, more commonly among women 20 years, black non-
Hispanic and Hispanic women, and those without high school education. Relative to
adequate care, inadequate care was associated with increased risk of prematurity 3.75
Keywords (3.73 to 3.77), stillbirth 1.94 (1.89 to 1.99), early neonatal dearth 2.03 (1.97 to 2.09),
► prenatal care late neonatal death 1.67 (1.59 to 1.76), and infant death 1.79 (1.76 to 1.82).
► risk factors Conclusion Risk of prematurity, stillbirth, early and late neonatal death, and infant
► pregnancy outcome death increased linearly with decreasing care. Given the population effect of this
► infant mortality association, public health initiatives should target program expansion to ensure timely
► population and adequate access, particularly for women 20 years, Black non-Hispanic and
characteristics Hispanic women, and those without high school education.

Adequate prenatal care (PNC) is a widely accepted determi-
nant of maternal and child health and a focus of public health
programming, despite ongoing controversy over whether
PNC prevents poor birth outcomes, particularly infant mor-
tality. PNC is considered adequate, based on the American
College of Obstetricians and Gynecologists guidelines for
prenatal visits in low-risk pregnancy, if it is initiated in the
first trimester with regular visits of increasing frequency as
term approaches.1 There is an absence of high-quality evi-
dence from randomized controlled trials to establish either

received Copyright © 2012 by Thieme Medical DOI http://dx.doi.org/

October 27, 2011 Publishers, Inc., 333 Seventh Avenue, 10.1055/s-0032-1316439.
accepted after revision New York, NY 10001, USA. ISSN 0735-1631.
February 29, 2012 Tel: +1(212) 584-4662.
published online
July 26, 2012
 RETURN TO TABLE OF CONTENTS
788 Inadequate Prenatal Care Utilization Partridge et al.
the overall benefit of PNC or what frequency or content of care
has maximal benefit. Observational and retrospective cohort
studies have yielded conflicting results: Some failed to estab-
lish prevention of poor outcomes,2–4 but others showed that
minimal or no PNC is associated with low birth weight,
preterm birth, or being small for gestational age.4–9 Trials
comparing reduced to standard PNC had insufficient power to
expose associations with infant mortality.10,11 Limitations in
the definition and measurement of adequate care may un-
derlie these conflicting results.
Despite dramatic declines in U.S. infant mortality rates over
the past 50 years, there has been an increasing disparity in
infant mortality rate by race and maternal education, which
has been thought to be in part due to discrepancies in access to
or utilization of adequate PNC.12 Unfortunately, given the
paucity of evidence measuring associations between PNC
and perinatal mortality, justification for public health initia-
tives promoting the implementation of programs increasing
access to timely and adequate PNC may be limited given the
increasing overall costs of health care in Westernized coun-
tries. The purpose of our study was thus to measure the rates of
inadequate PNC as defined by the Adequacy of Prenatal Care
Utilization (APNCU) index and estimate the magnitude of the
relationship between inadequate care and fetal and neonatal
mortality.13 We used a large administrative database of over
32 million births over 8 years to ensure sufficient power to
detect differences in mortality that may exist.
Materials and Methods
We conducted a retrospective cohort study for 8 consecutive
years, from 1995 to 2002, using the “Birth Cohort Linked
Birth-Infant Death” and the “Fetal Death” data files from the
National Center for Health Statistics (Centers for Disease
Control and Prevention). The birth cohort files contain infor-
mation on 3.5 million live births per year to residents and
nonresidents in the United States. This information is ob-
tained from the birth certificate and is available for all births.
The infant death file contains information on all infant deaths
in the United States and can be linked to its corresponding
birth record in the birth cohort through a unique identifier.
The fetal death cohort file contains the record on all fetal
deaths and can be readily appended to the live birth cohort
file to obtain a final cohort containing all deliveries, whether
born dead or alive. We selected from these databases all
records for the contiguous United States, Hawaii, and Alaska.
The territories Puerto Rico, Guam, and the Virgin Islands were
excluded from our cohort. Furthermore, our analysis did not
include births of U.S. citizens outside of the United States. This
resulted in an aggregate of 32,206,417 deliveries. We
then sequentially excluded all nonsingleton gestations
(1,287,495); deliveries that occurred prior to 22 weeks
(317,135) or after 44 weeks of gestational age (944,273)
and those with a congenital anomaly reported on the birth
certificate (1,244,884). This resulted in an 8-year cohort of
28,729,765 deliveries.
The variables used in this analysis were defined as follows.
The APNCU index is a sum of two independent dimensions:
American Journal of Perinatology Vol. 29 No. 10/2012
Adequacy of Initiation of PNC and Adequacy of Received
Services (a ratio of PNC visits completed relative to those
expected based on gestational age and the American Congress
of Gynecologists and Obstetricians recommended PNC sched-
ule for low-risk pregnancies). Deliveries were categorized by
receipt of, in increasing order of PNC utilization, “inadequate
care” (initiated after 4 months’ gestation or fewer than half of
predicted visits), “intermediate care” (initiated prior to
4 months and between 50% and 79% of expected visits),
“adequate care” (initiated by 4 months and 80 to 109% of
expected visits), or “adequate-plus care” (initiated by
4 months and 110% or more of expected visits). A final group,
“missing care data,” was created for cases where PNC ade-
quacy could not be calculated due to the absence of essential
information. The following variables were used to calculate
the APNCU with a previously published SAS algorithm dis-
tributed by Dr. Milton Kotelchuck, developer of the APNCU
index14,15: gestational age at initiation of PNC (2-month
intervals), total number of PNC visits (excluding hospital-
izations), and the gestational age in weeks. In the event of
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missing gestational age data, the gestational age was imputed
from the sex and birth weight. Improbable birth weight (less
than 250 g and more than 4999 g) was corrected for.
Birth outcomes included small for gestational age (SGA)
and intrauterine growth restriction (IUGR), respectively de-
fined as birth weight below the 10th and 3rd percentiles, and
large for gestational age (LGA), defined as birth weight above
the 90th percentile, using a standard reference developed for
male and female singleton births.16 Preterm birth was de-
fined as live birth under 37 weeks’ gestation. Stillbirth was
defined, based on the 1950 World Health Organization defi-
nition, as an intrauterine demise irrespective of the duration
of pregnancy and excluding all induced terminations of
pregnancy. Stillbirths with missing gestational age data
were proportionally distributed across gestational ages and
thus were unlikely to represent a significant confounding
factor. Early neonatal death was defined as any infant death
that occurred from birth to 7 days; late neonatal as death
between 7 and 27 days; and infant death as any fatality
between birth and 365 days of life. Deliveries that had
incomplete records were included in the analysis, through
the creation of dummy values to represent missing data.
Our analysis was conducted in three steps. First, we
performed descriptive statistics for the annual frequency
distribution of APNCU categories from 1995 to 2002. Second,
we did a sensitivity analysis to investigate the robustness of
our findings, as there was possible bias introduced by incom-
plete or inconsistent data collection. We examined the ma-
ternal and gestational characteristics of each APNCU class.
These characteristics were the maternal age (10-year inter-
vals), maternal race (white non-Hispanic, black non-Hispanic,
Hispanic, or other non-Hispanic), maternal education (in
years), marital status (married, not married), parity (zero,
one, two, three or more prior births), smoking during the
pregnancy (yes, no), and alcohol consumption during the
pregnancy (yes, no). Finally, we performed logistic regression
analysis to estimate the crude and adjusted odds ratio of eight
poor birth outcomes for each APNCU category. All outcomes
 RETURN TO TABLE OF CONTENTS
were modeled separately. We defined adequate care as the
reference group and calculated 95% confidence intervals. The
eight outcomes of interest were: SGA, IUGR, LGA, preterm
birth, stillbirth, early neonatal death, late neonatal death, and
infant death. All outcomes were adjusted for maternal age,
maternal race, maternal education, marital status, parity,
maternal smoking, or alcohol consumption during pregnan-
cy. All analyses were conducted using SAS version 9.2 (SAS
Institute, Cary, NC). This protocol was approved by the
Medical Research Ethics Department of the Jewish General
Hospital in Montreal, Quebec.
Results
Of the 32,206,417 births recorded during our 8-year study
period, 28,729,765 (89.2%) met the study inclusion criteria. In
the first analysis, we examined the frequency distribution of
deliveries from 1995 to 2002 by APNCU class. Despite annual
fluctuations in the relative proportions of each class, the
percent annual frequency of the intermediate and adequate
care groups was relatively stable over 8 years (►Fig. 1).
Inadequate care showed modest decreases each year, chang-
ing overall from 11.8% in 1995 to 10.74% in 2002; this was
offset by an increase in adequate-plus care from 27.6% in 1995
to 30.0% in 2002.
►Table 1 summarizes sociodemographic and gestational
characteristics by APNCU group. The proportion of mothers
receiving inadequate care was greatest among those under
15 and 15 to 19 years of age, black non-Hispanic or Hispanic,
not married, with less than 12 years of education, with three
or more prior live births, and with smoking or drinking
alcohol during the pregnancy. Among those who received
adequate care, there were proportionately more mothers
who were 30 to 39 years old, white non-Hispanic, married,
with greater than 16 years of education, who had one or fewer
prior live births. Most mothers received adequate care:
12,374,128 (43.1%).
Figure 1 Percent annual frequency by Adequacy of Prenatal Care Utilization (APNCU) class 1995–2002.
Inadequate Prenatal Care Utilization Partridge et al. 789
►Table 2 shows the odds ratio and frequency of stillbirth,
infant mortality, and adverse outcomes by APNCU category.
All outcomes were modeled separately; adequate care was
used as the reference, and results were significant with
p < 0.0001. Inadequate PNC was associated with increased
risk of all adverse outcomes. Stillbirth, early neonatal death,
late neonatal death, and infant death showed a linear increase
in risk with decreasing PNC relative to adequate care. There
was a bimodal distribution according to PNC, with the great-
est risks associated with the adequate-plus care and missing
care data groups. The adequate-plus care group had reduced
risk of IUGR and SGA and more risk of LGA; this group also had
a substantially increased risk of preterm birth. Adjusting for
confounding variables reduced risk estimates for all outcomes
(nonadjusted data not reported).
►Table 3 shows a subgroup analysis of 27,900,165 births at
34 or more weeks’ gestation, with odds ratio and frequency of
stillbirth, early neonatal death, late neonatal death, and infant
death by APNCU category. All outcomes were modeled and
corrected for in a fashion identical to the analysis in ►Table 2
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and were significant with p < 0.0001. The linear relationship
between risk of adverse outcome and decreasing PNC was
preserved; however, the odds ratios were notably smaller.
Discussion
Adequacy of PNC utilization is an important predictor of
maternal and fetal health. Over an 8-year span from 1995
to 2002, a consistent annual decrease in rates of inadequate
care was offset by a rise in rates of adequate-plus care. The
proportion of mothers receiving inadequate care was greatest
among women under 20 years of age who were black non-
Hispanic or Hispanic, were not married, had less than 12 years
of education, had three or more prior live births, and smoked
or drank alcohol during the pregnancy. Inadequate PNC was
associated with increased risk for all adverse outcomes of
interest. Risk of prematurity, stillbirth, early neonatal death,
American Journal of Perinatology Vol. 29 No. 10/2012
 RETURN TO TABLE OF CONTENTS

790 Inadequate Prenatal Care Utilization Partridge et al.

Table 1 Baseline Characteristics by APNCU Prenatal Care Category

APNCU Category
Missing Care Data Inadequate Care Intermediate Care Adequate Care Adequate-Plus Care
(n ¼ 1,063,776), % (n ¼ 3,224,001), % (n ¼ 3,765,225), % (n ¼ 12,374,128), % (n ¼ 8,302,635), %
Age (y)
<15 5.6 32.1 11.8 27.1 23.4
15–19 4.5 20.3 13.5 35.8 26.0
20–29 3.7 11.7 53.0 42.8 28.5
30–39 3.4 7.0 12.7 46.5 30.4
>39 4.0 9.4 11.6 41.2 33.7
Race
White non-Hispanic 2.7 7.3 12.6 47.3 30.1
Black non-Hispanic 5.7 18.4 12.4 34.0 29.5
Hispanic 4.8 17.4 14.7 37.3 25.8
Other non-Hispanic 3.9 12.6 14.6 42.5 26.5
Unknown 10.2 9.9 15.1 41.3 23.5
Marital status

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Married 3.1 7.1 13.0 46.7 30.0
Not married 4.9 19.6 13.4 35.6 26.5
Maternal education (y)
0–8 4.8 25.1 15.5 32.4 22.1
9–11 4.6 21.2 14.0 34.5 25.6
12 3.7 11.8 13.1 42.0 29.3
13–15 2.9 7.2 12.5 46.0 31.3
>16 2.6 3.6 12.4 50.9 30.5
Prior live births
None 3.5 9.8 12.8 44.1 29.8
One 3.3 9.6 13.2 44.7 29.2
Two 3.7 12.2 13.5 42.2 28.4
Three or more 4.7 20.2 14.0 35.9 25.1
Smoking during pregnancy
Yes 3.8 16.6 13.1 38.0 28.4
No 3.8 10.6 13.0 43.7 28.9
Alcohol during pregnancy
Yes 5.1 23.7 13.1 35.3 22.7
No 3.8 11.2 13.1 43.2 28.7

Table values are percentages rounded to one decimal, thus not all rows sum to 100%.

late neonatal death, and infant death increased linearly with
decreasing PNC. Inadequate PNC utilization was associated
with an increased risk of poor birth outcomes; however,
patients with above-adequate care and missing PNC data
also had substantial risk.
To date the most widely used indices of PNC utilization are
the Kessner and the APNCU Index. The Kessner Index was
developed in 197317 and largely did not show differences in
outcome between groups, possibly secondary to inadequate
separation of groups.15 In the 1990s, Kotelchuck proposed the
APNCU Index as a modification of the Kessner: Its most
interesting contribution is the distinction of patients with
adequate-plus care who previously had been included in the
adequate care group. The adequate-plus care group has since
been demonstrated to have poor birth outcomes, and it has
been suggested that inclusion of high-risk patients in the
reference group may have obscured relationships between
PNC and outcome.13 The APNCU has also been shown to
generate a smaller inadequate care group than the Kessner,
which is likely a more precise categorization.18 For these
reasons, we elected to use the APNCU Index.
Our finding of a significant association between PNC and
infant mortality is consistent with that of a random sample
from the 2003 Centers for Disease Control birth cohort, where
inadequate care had a twofold increase in risk of infant
mortality relative to adequate care.19 Our finding of a linear
relationship between decreasing PNC and increasing risk of
stillbirth, early neonatal death, late neonatal death, and infant

American Journal of Perinatology Vol. 29 No. 10/2012

 Table 2 OR and Frequency of Outcome by APNCU Prenatal Care Category for the 1995–2002 Singleton Birth Cohort (n ¼ 28,729,765)

APNCU Category
Missing Care Data Inadequate Care Intermediate Care Adequate Care Adequate-Plus Care
(n ¼ 1,063,776) (n ¼ 3,224,001) (n ¼ 3,765,225) (n ¼ 12,374,128) (n ¼ 8,302,635)
% OR (95% CI) % OR (95% CI) % OR (95% CI) % Reference % OR (95% CI)
Preterm birth 16.3 4.77 (4.74–4.81) 13.3 3.75 (3.73–3.77) 3.5 1.05 (1.04–1.06) 3.1 1 22.5 9.10 (9.07–9.13)
IUGR 5.3 1.10 (1.09–1.11) 6.3 1.30 (1.29–1.31) 5.7 1.48 (1.47–1.49) 3.7 1 3.1 0.78 (0.78–0.79)
SGA 8.5 1.03 (1.02–1.04) 9.7 1.11 (1.11–1.12) 9.4 1.26 (1.25–1.27) 7.2 1 6.1 0.80 (0.79–0.80)
LGA 12.2 1.20 (1.19–1.21) 11.6 1.20 (1.19–1.20) 8.7 0.80 (0.80–0.80) 10.7 1 17.4 1.80 (1.79–1.80)
Stillbirth 1.0 1.07 (1.03–1.10) 0.7 1.94 (1.89–1.99) 0.3 1.21 (1.18–1.25) 0.3 1 0.6 2.24 (2.20–2.29)
Early neonatal death 0.6 4.44 (4.29–4.59) 0.2 2.03 (1.97–2.09) 0.1 1.20 (1.16–1.24) 0.1 1 0.3 3.07 (3.00–3.14)
Late neonatal death 0.1 2.80 (2.63–2.98) 0.1 1.67 (1.59–1.76) 0.0 1.08 (1.02–1.15) 0.0 1 0.1 2.52 (2.43–2.61)
Infant death 1.0 2.83 (2.77–2.90) 0.7 1.79 (1.76–1.82) 0.3 1.14 (1.12–1.17) 0.3 1 0.6 2.22 (2.19–2.26)

Each outcome modeled separately. All p <0.0001. Adjusted for maternal race, maternal age, marital status, maternal education, prior live births, and maternal smoking and maternal alcohol in pregnancy. APNCU,
Adequacy of Prenatal Care Utilization; CI, confidence interval; IUGR, intrauterine growth restriction; LGA, large for gestational age; OR, odds ratio; SGA, small for gestational age.

Table 3 Births at 34 or More Weeks’ Gestation: OR and Frequency of Outcome by APNCU Prenatal Care Category for the 1995–2002 Singleton Birth Cohort (n ¼ 27,900,165)
RETURN TO TABLE OF CONTENTS

APNCU Category
Missing Care Data Inadequate Care Intermediate Care Adequate Care Adequate-Plus Care
(n ¼ 1,063,776) (n ¼ 3,224,001) (n ¼ 3,765,225) (n ¼ 12,374,128) (n ¼ 8,302,635)
% OR (95% CI) % OR (95% CI) % OR (95% CI) % Reference % OR (95% CI)
Stillbirth 0.47 0.68 (0.66–0.72) 0.24 1.76 (1.69–1.82) 0.16 1.32 (1.27–1.38) 0.11 1 0.16 1.46 (1.41–1.50)
Early neonatal death 0.09 2.27 (2.11–2.45) 0.06 1.72 (1.62–1.82) 0.04 1.23 (1.16–1.30) 0.03 1 0.05 1.63 (1.56–1.71)
Late neonatal death 0.05 1.60 (1.45–1.77) 0.05 1.45 (1.36–1.55) 0.03 1.11 (1.04–1.19) 0.03 1 0.04 1.42 (1.34–1.49)
Inadequate Prenatal Care Utilization

American Journal of Perinatology

Infant death 0.36 1.59 (1.53–1.65) 0.42 1.56 (1.53–1.60) 0.23 1.14 (1.11–1.17) 0.18 1 0.25 1.34 (1.32–1.37)

Each outcome modeled separately. All p <0.0001. Adjusted for maternal race, maternal age, marital status, maternal education, prior live births, maternal smoking and maternal alcohol in pregnancy. APNCU,

Vol. 29
Adequacy of Prenatal Care Utilization; CI, confidence interval; OR, odds ratio.

No. 10/2012
Partridge et al.
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 RETURN TO TABLE OF CONTENTS
792 Inadequate Prenatal Care Utilization Partridge et al.
death supports a direct relationship. The relative risks of
adverse neonatal and infant outcomes by APNCU class were
smaller in a subgroup analysis of births at 34 or more weeks’
gestation, suggesting that an association between inadequate
PNC and prematurity is involved in some poor outcomes.
The relationship between level of PNC and birth outcomes can
be accounted for in a variety of ways. Some components of
PNC are clearly protective, such as diagnosis and treatment of
maternal genital tract infection,20 HIV infection,21 or promo-
tion of exclusive breast-feeding.22 Another possibility is that a
maternal factor, such as care-seeking behavior, could, in
association with other health-promoting behaviors, account
for differential risk.2,23 This possibility is reinforced by evi-
dence that utilization of PNC is associated with increased
utilization of preconception care, infant care, and infant
vaccination.24–26 This “healthy adherer bias” was recently
described through a meta-analysis showing that patients who
adhere to drug therapy have lower all-cause mortality, even
when that therapy is a placebo, suggesting that patient
adherence may itself be a surrogate for health-promoting
behaviors.27 Adoption of PNC is likely multifactorial and can
be predicted by factors such as having an unplanned preg-
nancy, late recognition of pregnancy, race, socioeconomic
status, and geographic location.28–31 Demographic character-
istics disproportionately prevalent in the inadequate care
group likely reflect underlying heterogeneity in this group,
ranging from mothers under 15 years of age to multiparous
women who may not appreciate the need for PNC.
Our study showed that women with adequate-plus PNC
have an increased risk of perinatal mortality. It has previously
been suggested that this group contains disproportionately
more identified high-risk pregnancies that required more
prenatal visits and subsequent interventions.13,15 This possi-
bility is supported by our finding that this group also had
increased risk of LGA, perhaps reflecting macrosomic infants
of diabetic mothers who are likely to be more closely followed
both before and during the pregnancy than women who were
not diabetic. There may also be an iatrogenic contribution to
poor birth outcomes seen with above-adequate PNC: Mater-
nal care providers who are categorized as “more aggressive
testers” have a greater incidence of low birth weight, even
after risk factors were controlled for.32
An element of all studies that use large administrative
databases is the treatment of missing data. In their analysis of
Californian births, Gould et al found that incomplete records
were an independent and linearly related risk marker for
infant mortality.33 For this reason, we did not exclude
deliveries with incomplete records from our analysis and
elected to treat those with missing PNC data as a separate
subset of the population. This missing care data group had
the highest relative risk for early and late neonatal and infant
death. This relatively small subpopulation, with 1,063,776
deliveries over 8 years, may represent an important subset of
high-risk mothers who are largely unknown to the health
care system or a bias toward underdocumentation in some at
risk groups. With respect to cases where PNC data were
available, our results remained significant despite the inclu-
sion of missing variables and likely underrepresent the true
American Journal of Perinatology Vol. 29 No. 10/2012
relative risk, as the bias of inclusion of missing data are
toward the null.
One limitation of the APNCU index is a previously de-
scribed gestational age bias. Gestational age affects categori-
zation within the index and could be expected to have a
greater effect on some outcomes of interest, such as low birth
weight, than adequacy of PNC. Short gestation may result in
delivery before the opportunity to initiate care or misclassi-
fication in the adequate-plus category, as fewer visits are
recommended in early pregnancy and 110% utilization could
be met with one extra visit. Postdate gestations would require
more visits and thus be less likely to meet criteria for inclusion
in the adequate-plus group. Our finding of a ninefold increase
in preterm birth for the adequate-plus group relative to the
adequate group likely reflects this bias, and caution should be
used in the interpretation of prematurity risks in this context.
Gestational age bias can be overcome by the use of dependant
variables that correct for gestational age, such as SGA in place
of low birth weight,10,19,34,35 as we did in this study. A
comparison of four adequacy of care indices, including the
Downloaded by: University of Cincinnati. Copyrighted material.
Kessner and the APNCU, showed comparable association
between PNC and SGA across indices, demonstrating the
robustness of this measure.19
Limitations of this study include the potential for an
ecological fallacy, whereby relationships between PNC and
outcome for the U.S. population as a whole may not apply to
subpopulations; there is evidence that some groups are at
greater risk for poor birth outcomes in the absence of PNC,
and these relationships bear further investigation.36 Use of
birth and death certificate data limited our assessment to an
analysis of adequacy as defined by utilization, rather than the
content of PNC. Reporting bias is also possible, as an indepen-
dent assessment of the quality of national birth record data
was not performed, and misclassification and measurement
error have previously been reported with birth certificate
data: 5.1% of prenatal visits were missing in birth certificates
relative to chart review in a sample of low-risk pregnancies in
Washington state from 1988 to 1989.37 In a study comparing
birth certificate data to medical records in New York for 1999,
the date of initiation of care was concordant within 1 week
for 76% of records; however, there was only a 38% absolute
concordance for the number of prenatal visits, which in-
creased to 70% with a two-visit range; last, the last menstrual
period was correct 87% of the time and was 93% accurate with
a 1-week range.38 Fortunately the large sample size this data
affords was sufficient to expose significant associations even
with this source of statistical noise. Our study is, however,
unique in that it has considerable power to find associations
with relatively rare outcomes.
In conclusion, this is the largest population-based cohort
study to date to evaluate the association between adequacy of
PNC utilization and the risk of adverse outcomes. We found a
strong linear association between inadequate PNC and in-
creased risk of prematurity, stillbirth, and neonatal and infant
mortality. This increase in risk may have a small effect for
individual mothers, but the population-level effect in a
country with more than 3.5 million annual singleton deliver-
ies is substantial. Mothers who disproportionately receive
 RETURN TO TABLE OF CONTENTS
inadequate care were under 20 years of age, black non-
Hispanic and Hispanic women, and those without high school
education. Given the population effect of this association,
public health initiatives should target program expansion to
ensure timely and adequate access to adequate PNC, particu-
larly for women at risk.
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between adequacy of prenatal care utilization and subsequent
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Gálvez-Vargas R. Unplanned pregnancy as a major determinant
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36 Murray JL, Bernfield M. The differential effect of prenatal care on
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37 Dobie SA, Baldwin LM, Rosenblatt RA, Fordyce MA, Andrilla CH,
Hart LG. How well do birth certificates describe the pregnancies
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American Journal of Perinatology Vol. 29 No. 10/2012
 RETURN TO TABLE OF CONTENTS

The Preterm Prediction Study: Effect of gestational age and

cause of preterm birth on subsequent obstetric outcome
Brian M. Mercer, MD, Robert L. Goldenberg, MD, Atef H. Moawad, MD, Paul J. Meis, MD, Jay D.
Iams, MD, Anita F. Das, MS, Steve N. Caritis, MD, Menachem Miodovnik, MD, M. Kathryn
Menard, MD, Gary R. Thurnau, MD, Mitchell P. Dombrowski, MD, James M. Roberts, MD, and
Donald McNellis, MD, for the National Institute of Child Health and Human Development
Maternal-Fetal Medicine Units Network

OBJECTIVE: We sought to evaluate the association between prior spontaneous preterm delivery and sub-
sequent pregnancy outcome.
STUDY DESIGN: A total of 1711 multiparous women with singleton gestations were prospectively evaluated
at 23 to 24 weeks’ gestation. Prior pregnancies were coded for the presence or absence of a prior sponta-
neous preterm delivery. If a prior spontaneous preterm delivery had occurred, the gestation of the earliest
prior delivery (13-22, 23-27, 28-34, and 35-36 weeks’ gestation) was recorded. Current gestations were cate-
gorized as spontaneous preterm delivery at <28, <30, <32, <35, or <37 weeks’ gestation. The risk of sponta-
neous preterm delivery in the current gestation was determined on the basis of the occurrence, gestational
age, and cause of the earliest prior spontaneous preterm delivery.
RESULTS: The incidences of spontaneous preterm delivery before 28, 30, 32, 35, and 37 weeks’ gestation
were 0.8%, 1.1%, 1.9%, 5.1%, and 11.9%, respectively. Those with a prior spontaneous preterm delivery
carried a 2.5-fold increase in the risk of spontaneous preterm delivery in the current gestation over those
with no prior spontaneous preterm delivery (21.7% vs 8.8%; P ≤ .001). Gravid women with an early prior
spontaneous preterm delivery (23-27 weeks’ gestation) had a higher risk of recurrent spontaneous preterm
delivery (27.1% vs 8.8%; P ≤ .001). Prior spontaneous preterm delivery was more closely associated with
subsequent early spontaneous preterm delivery at <28 weeks’ gestation (relative risk, 10.6) than for sponta-
neous preterm delivery overall (relative risk, 2.5). An early prior spontaneous preterm delivery (23-27 weeks’
gestation) was most highly associated with early spontaneous preterm delivery (<28 weeks’ gestation) in the
current gestation (relative risk, 22.1). The relationship between prior spontaneous preterm delivery and cur-
rent outcome was not as strong for those with a very early spontaneous preterm delivery (13-22 weeks’ ges-
tation). Prior spontaneous preterm delivery caused by preterm premature rupture of the membranes and
preterm labor was significantly associated with similar outcomes in the current gestation (P < .001).
CONCLUSION: Prior spontaneous preterm delivery is highly associated with recurrence in the current ges-
tation. An early prior spontaneous preterm delivery is more predictive of recurrence and is most highly asso-
ciated with subsequent early spontaneous preterm delivery. (Am J Obstet Gynecol 1999;181:1216-21.)

Key words: Prematurity; preterm birth; fetal membranes, premature rupture; prediction

Spontaneous preterm delivery caused by preterm labor
or premature rupture of the membranes accounts for
80% to 84% of preterm low-birth-weight infants, with
preterm labor accounting for approximately 50% and
preterm premature rupture of the membranes account-
ing for 33% of preterm deliveries.1-4 A number of investi-
A complete list of members of the National Institute of Child Health and
Human Development Maternal-Fetal Medicine Units Network and their
institutional affiliations appears at the end of the article.
Supported by grants HD-21410, HD-21414, HD-21434, HD-27860,
HD-27861, HD-27869, HD-27883, HD-27889, HD-27905, HD-
27915, HD-27917, and HD-19897 from the National Institute of
Child Health and Human Development, Bethesda, Maryland.
Received for publication February 12, 1999; revised April 1, 1999; ac-
cepted May 21, 1999.
Reprints not available from the authors
6/1/100144
gators have evaluated clinical risk scoring systems for the
identification of populations at risk for preterm
delivery.5-10 A history of preterm delivery has frequently
been cited as a potential predictor of subsequent out-
come.4, 5, 11-16 The risk of preterm birth appears to in-
crease with an increasing number of prior adverse out-
comes.7, 9, 10 Moreover, early preterm delivery may be
associated with an increased risk of subsequent prematu-
rity.12-15 However, the effects of the gestational age of the
prior preterm birth and the cause of that delivery have
not been fully evaluated.
The National Institute of Child Health and Human
Development Preterm Prediction Study is a population-
based observational study with the goal of identifying his-
torical, clinical, and laboratory markers that are predic-
tive of spontaneous preterm birth caused by either

1216
 RETURN TO TABLE OF CONTENTS
Volume 181, Number 5, Part 1
Am J Obstet Gynecol
preterm labor or preterm premature rupture of the
membranes. We hoped to identify relationships between
these markers that would improve the predictive value of
individual tests or help elucidate the mechanisms lead-
ing to preterm birth. The principal analyses of the study’s
results have been reported.17-21 In a recent analysis we
found women with a prior preterm birth to have signifi-
cant additional risk of recurrence if there was a positive
fetal fibronectin screen or a short cervix on vaginal ultra-
sonography in the subsequent gestation.22
The purpose of this secondary analysis is to further
evaluate the relationship between the gestational age of
the earliest prior spontaneous preterm delivery and sub-
sequent pregnancy outcome. Additionally, we evaluate
the importance of the cause of prior spontaneous
preterm birth on preterm birth in the current gestation.
Methods
This evaluation includes multiparous women partici-
pating in a prospective study of 3073 gravid women from
10 centers of the Maternal-Fetal Medicine Units Network
of the National Institute of Child Health and Human
Development. The study was approved by each center’s
institutional review board, and each participant provided
written consent. Women without symptoms and with sin-
gleton gestations were evaluated at 23 to 24 weeks’ gesta-
tion. For the purpose of this analysis, multiparous women
were defined as women with at least one prior preterm or
term delivery (≥20 weeks 0 days).
All women underwent ultrasonography to rule out pla-
centa previa and major fetal malformations before en-
rollment. Other exclusion criteria for the Preterm
Prediction Study were as follows: cervical cerclage, poly-
hydramnios, oligohydramnios, and cervical dilatation of
≥2 cm for nulliparous women and ≥3 cm for multiparous
women. Gestational age was determined according to the
onset of the last menstrual period or on the basis of the
earliest ultrasonographic estimation of gestational age in
the absence of a reliable last menstrual period date. If sig-
nificant discordance was identified between ultrasonog-
raphy and last menstrual period dating (ie, ≥10 days for
the purpose of this study), ultrasonographic estimation
was used to assign gestational age.
Each participant underwent a detailed structured in-
terview in a private office. The interview was designed to
ascertain information regarding demographic factors, so-
cioeconomic status, home and work environment, drug
or alcohol use, and medical and obstetric history.
Participants were questioned in a standardized fashion
regarding symptoms, positive cultures, treatments and
medications, hospitalizations, and restriction of activity
during the current gestation. Medical history and prior
and current obstetric information were documented
through review of the participant’s medical record.
When a history of preterm birth or low birth weight was
Mercer et al 1217
Table I. Demographic and baseline characteristics of
1711 multiparous women participating in study
Age (y, mean) 25.5 ± 5.4
Race
African American (%) 65.3
White (%) 33.2
Other (%) 1.5
Married (%) 33.8
Unmarried living with an adult (%) 40.7
Schooling ≥13 y (%) 26.7
Smoking (%) 33.8
Alcohol use (%) 13.0
Illicit drug use (%) 5.4
Gravidity (median) 3
Parity (median) 1
≥1 prior first-trimester miscarriage (%) 26.1
≥1 prior second-trimester miscarriage (%) 3.9
≥1 prior spontaneous preterm delivery (%) 24.0
Gestation at first prenatal visit (wk, mean ± SD) 11.1 ± 4.4
obtained, the gestational age at the prior preterm birth
was documented through medical record review where
possible, and the birth was characterized as having oc-
curred after preterm labor, after spontaneous premature
rupture of the membranes before labor, or because of
maternal or fetal indication necessitating birth. In addi-
tion, screening for bacterial vaginosis and cervicovaginal
fetal fibronectin, as well as transvaginal ultrasonography
for cervical length, was performed at 23 to 24 weeks’ ges-
tation. The patient’s caregivers were blinded to these re-
sults, which are reported elsewhere.18-21
Patients were followed prospectively, and the current
pregnancy was evaluated for spontaneous preterm deliv-
ery. Women with a prior spontaneous preterm delivery
caused by preterm labor or a spontaneous preterm deliv-
ery caused by preterm rupture of the membranes were
evaluated separately for risk of spontaneous preterm de-
livery of the same cause in the current gestation.
Additionally, the presence of a prior spontaneous
preterm delivery of either cause was correlated with
spontaneous preterm delivery in the current gestation.
For the purpose of this analysis, the prior preterm birth
with the earliest gestational age at delivery was used irre-
spective of chronologic order. Statistical analysis was per-
formed by using SAS (SAS Institute, Inc, Cary, NC) statis-
tical software. Descriptive statistics, the χ2 test, and the
Fisher exact test were used where appropriate. Relative
risks with 95% confidence intervals were calculated. A
nominal P value of < .05 was considered statistically sig-
nificant.
Results
Of 3073 women recruited into the study between
October 1992 and July 1994, 71 (2.4%) were lost to fol-
low-up, and 73 were initially evaluated outside the pre-
scribed 23- to 24-week gestational age limit. Among the
remaining 2929 women, 1711 were multiparous (58.4%),
 RETURN TO TABLE OF CONTENTS

1218 Mercer et al November 1999

Am J Obstet Gynecol

Table II. Risk of spontaneous preterm delivery before defined gestations in current pregnancy on basis of gestational
age at earliest prior spontaneous preterm delivery associated with preterm premature rupture of membranes or
preterm labor
Gestation of earliest prior preterm delivery

Gestation No prior 13-22 wk 23-27 wk 28-34 wk 35-36 wk Any prior preterm

at delivery preterm (n = 98) (n = 59) (n = 167) (n = 86) delivery (N = 410)
in current delivery
pregnancy (n = 1301) Relative Relative Relative Relative Relative
(wk) (%) % risk % risk % risk % risk % risk

<28 0.23 1.0 4.4 5.1 22.1* 3.0 13.0† 1.2 5.0 2.4 10.6†
<30 0.46 2.0 4.4 5.1 11.0* 3.6 7.8* 1.2 2.5 2.9 6.4†
<32 0.85 3.1 3.6 10.2 12.0† 5.4 6.4† 3.5 4.1 5.1 6.1†
<35 2.5 8.2 3.3* 20.3 8.3† 14.4 5.8† 12.8 5.2† 13.4 5.5†
<37 8.8 15.3 1.7‡ 27.1 3.1† 24.0 2.7† 20.9 2.4† 21.7 2.5†

Relative risks are for spontaneous preterm delivery in current gestation compared with risk for gravid women with no prior sponta-
neous preterm delivery.
*P < .01.
†P ≤ .001.
‡P < .05.

and 1218 (41.6%) were nulliparous. Demographic, ob-
stetric, and gynecologic characteristics of the multi-
parous women are shown in Table I. In the current gesta-
tion spontaneous preterm delivery occurred before 37,
35, 32, 30, and 28 weeks’ gestation in 11.9%, 5.1%, 1.9%,
1.1%, and 0.8% of pregnancies, respectively. The inci-
dence of clinically diagnosed amnionitis was 2.0%, 6.6%,
and 23.5% with delivery at 35 to 36, 28 to 34, and 23 to 27
weeks’ gestation, respectively. A significant increase in
amnionitis was seen between 28 and 34 weeks’ gestation,
with those delivering at 32 to 34 weeks’ gestation having a
2.7% incidence and those delivering at 28 to 31 weeks’
gestation having a 16.1% incidence.
Effect of prior spontaneous preterm delivery on the cur-
rent pregnancy. Table II illustrates the risk of sponta-
neous preterm delivery at various cutoff points in the cur-
rent gestation on the basis of the gestation of earliest
prior spontaneous preterm delivery. Women with any
prior spontaneous preterm delivery carried a 2.5-fold in-
crease (95% confidence interval, 1.9-3.2) in risk of spon-
taneous preterm delivery before 37 weeks’ gestation in
the current gestation (21.7% vs 8.8%; P < .001). Prior
spontaneous preterm delivery was more closely associ-
ated with early preterm delivery in the current gestation.
Gravid women with a prior spontaneous preterm delivery
carried a 10.6-fold increase (95% confidence interval,
2.9-38.3) in relative risk of spontaneous preterm delivery
before 28 weeks in the current gestation (2.4% vs 0.23%;
P < .001).
Effect of timing of prior spontaneous preterm delivery
on the current pregnancy. The risk of spontaneous
preterm delivery before 37 weeks in the current gestation
increased with decreasing gestational age of the earliest
prior spontaneous preterm delivery. A prior spontaneous
preterm delivery at 23 to 27 weeks’ gestation carried the
highest risk of spontaneous preterm delivery in the cur-
rent gestation (relative risk, 2.4, 2.7, and 3.1 for earliest
prior delivery at 35-36, 28-34, and 23-27 weeks’ gestation,
respectively). A similar pattern was identified when early
spontaneous preterm delivery in the current gestation
was considered. There was an increasing relative risk of
spontaneous preterm delivery before 35, 32, 30, and 28
weeks’ gestation with earlier prior spontaneous preterm
delivery (Table II). The strongest association between his-
tory and current outcome was found between early prior
spontaneous preterm delivery (23-27 weeks’ gestation)
and early delivery in the current gestation (<28 weeks’
gestation), with a 22.1-fold increase (95% confidence in-
terval, 4.6-106.9) in relative risk for early delivery (5.1% vs
0.23%; P = .001).
Although a prior previable pregnancy loss (13-22
weeks’ gestation) was associated with an increased risk of
spontaneous preterm delivery in the current gestation
and carried a higher relative risk of earlier delivery, the
association was not as strong as for that seen with prior
deliveries subsequent to fetal viability. Further evaluation
of the entire study population revealed 69 women with
prior losses at 13 to 22 weeks’ gestation but no other
preterm deliveries. Analysis of these women failed to
identify an increased risk of preterm delivery in this pop-
ulation when compared with those having no prior spon-
taneous preterm delivery (10.1% vs 8.8%; P = .69). Those
with an earliest delivery at 13 to 18 weeks’ gestation had
an 8.7% risk of preterm birth (relative risk, 1.0; P = 1.0) in
the current gestation, whereas those with a prior earliest
delivery at 19 to 22 weeks’ gestation had a 12.5% risk (rel-
ative risk, 1.4; P = .46).
Effect of cause of prior spontaneous preterm delivery on
the current pregnancy. Tables III and IV illustrate the risk
of spontaneous preterm delivery caused by preterm labor
and caused by preterm premature rupture of the mem-
branes, respectively, in the current gestation on the basis
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Volume 181, Number 5, Part 1 Mercer et al 1219

Am J Obstet Gynecol

Table III. Incidence of spontaneous preterm delivery caused by preterm labor in current pregnancy on basis of pres-
ence or absence of spontaneous preterm delivery caused by preterm labor in a prior gestation
Gestation
at delivery Prior spontaneous No prior spontaneous
in current preterm delivery caused preterm delivery caused
pregnancy by preterm labor by preterm labor 95% Confidence
(wk) (n = 274) (%) (n = 1437) (%) Relative risk interval

<28 1.8* 0.21 8.7 2.1-36.4

<30 2.2* 0.42 5.3 1.7-16.1
<32 3.3* 0.77 4.3 1.8-10.3
<35 7.3† 2.0 3.8 2.1-6.6
<37 12.4† 5.8 2.2 1.5-3.1

*P < .01.
†P ≤ .001.

Table IV. Incidence of spontaneous preterm delivery caused by preterm premature rupture of membranes in current
pregnancy on basis of presence or absence of spontaneous preterm delivery caused by preterm premature rupture of
membranes in a prior gestation
Gestation
at delivery Prior spontaneous No prior spontaneous
in current preterm delivery caused preterm delivery caused
pregnancy by preterm labor by preterm labor 95% Confidence
(wk) (n = 171) (%) (n = 1540) (%) Relative risk interval

<28 1.8* 0.13 13.5 23.0-80.3

<30 2.3* 0.13 18.0 3.3-97.6
<32 2.9* 0.45 6.4 2.1-20.0
<35 8.2† 1.6 5.0 2.7-9.5
<37 13.5† 4.1 3.3 2.1-5.2

*P < .01.
†P ≤ .001.

of the presence or absence of a similar outcome in a Comment

prior gestation. The incidences of spontaneous preterm
delivery caused by preterm labor and spontaneous
preterm delivery caused by spontaneous preterm rupture
of the membranes before labor among multiparous
women in the current gestation were 6.8% and 5.0%, re-
spectively. Those women with a history of spontaneous
preterm delivery caused by preterm labor carried a 2.2-
fold increase in risk of spontaneous preterm delivery
caused by preterm labor in the current gestation (12.4%
vs 5.8%; P < .001, Table III). Prior spontaneous preterm
delivery caused by preterm labor was more closely associ-
ated with early preterm delivery in the current gestation,
with a relative risk of 8.7 for spontaneous preterm deliv-
ery before 28 weeks’ gestation (1.8% vs 0.21%; P < .01). A
prior spontaneous preterm delivery caused by sponta-
neous preterm rupture of the membranes before labor
significantly increased the risk of preterm delivery
caused by preterm premature rupture of the membranes
in the current gestation (13.5% vs 4.1%; relative risk, 3.3;
P < .001; Table IV). Furthermore, a prior spontaneous
preterm delivery caused by spontaneous preterm rupture
of the membranes before labor was highly associated
with delivery caused by preterm premature rupture of
the membranes before 28 weeks in the current gestation
(1.8% vs 0.13%; relative risk, 13.5; P < .01).
The correlation between prior preterm birth and sub-
sequent preterm delivery has been described previously.5-16
Such a history has been given significant weight in clini-
cal risk scoring systems for the prediction of premature
delivery.5, 8, 9 In a separate multivariate analysis we have
confirmed that the number of previous preterm deliver-
ies correlates with preterm delivery in the current preg-
nancy.20 In this analysis we demonstrate that a prior
spontaneous preterm delivery caused by preterm labor
or premature rupture of the membranes is associated
with an increased risk of spontaneous prematurity in the
current gestation. Both preterm labor and preterm pre-
mature rupture of the membranes are individually asso-
ciated with similar outcomes in subsequent gestations. In
addition, a history of spontaneous preterm delivery is
more closely associated with early preterm than late
preterm delivery in the current gestation, and a prior
early preterm delivery is more predictive than a late
preterm delivery. In our study gravid women with any
prior spontaneous preterm delivery carried a 2.5-fold in-
creased risk of spontaneous preterm delivery in the cur-
rent gestation and a 10.6-fold increased risk of sponta-
neous preterm delivery before 28 weeks’ gestation.
Those with a prior early preterm delivery (23-27 weeks’
gestation) had a 22-fold increased risk of delivery before
 RETURN TO TABLE OF CONTENTS
1220 Mercer et al
28 weeks’ gestation in the current pregnancy. Although
we note that the confidence interval about this estimate
is broad because of the infrequency of recurrent early
preterm delivery, there was a consistent trend toward in-
creasing risk of spontaneous preterm delivery and early
spontaneous preterm delivery with decreasing gestation
of earliest prior delivery. For multiparous women evalu-
ated in this study, the incidence of clinical amnionitis in-
creased with decreasing gestational age at delivery. This
finding supports microbiologic and histologic data from
previous studies regarding preterm birth.23-25 We pro-
pose that an early preterm delivery serves as a marker for
a population at increased risk of preterm delivery be-
cause of either ongoing infection or increased suscepti-
bility to recurrent intrauterine infection in subsequent
gestations.
In this study a prior loss at 13 to 22 weeks’ gestation
was not as strongly correlated with subsequent preterm
delivery as that seen with prior preterm delivery subse-
quent to 23 weeks’ gestation. The finding that women
with prior losses at 13 to 22 weeks’ gestation but no other
preterm deliveries were not at increased risk for preterm
delivery (10.1% vs 8.8%; P = .69) is at variance with other
studies that suggest an increased risk after second-
trimester pregnancy loss.5, 8, 12-14 Goldenberg et al14 eval-
uated 78 women with pregnancy loss at 13 to 22 weeks’
gestation. Those with a loss at 19 to 22 weeks’ gestation
had a 62.1% risk of a preterm delivery in the next preg-
nancy compared with a 13.5% risk for those with a term
delivery in the index pregnancy (relative risk, 4.6; 95%
confidence interval, 3.4-6.2). Alternatively, those with a
loss at 13 to 18 weeks’ gestation in the index pregnancy
had a 22.5% risk of prematurity (relative risk, 1.7; 95%
confidence interval, 1.0-2.8). Although the gestational
age cutoff point between the 2 studies is slightly differ-
ent, both studies found that losses early in the second
trimester were less likely to be followed by a preterm
birth than losses that occurred later in the second
trimester. The fact that infection is highly associated with
preterm birth around 24 weeks’ gestation supports the
belief that the repetitive early preterm births may be re-
lated to infection. The findings of Goldenberg et al14
may be more sensitive in delineating this relationship be-
cause consecutive gestations were studied. Nevertheless,
it is possible that our findings reflect differences in the
pathologic processes leading to pregnancy loss before
the current limit of fetal viability and those occurring
subsequently. Perhaps abnormal placentation rather
than infection is the predominant abnormality with early
midtrimester loss and is less likely to recur in subsequent
pregnancies.
In summary, we have found gestational age of the ear-
liest prior delivery to be predictive of a similar adverse
outcome in subsequent gestations. Prior preterm deliv-
ery caused by either preterm labor or preterm premature
November 1999
Am J Obstet Gynecol
rupture of the membranes carries a similar risk for recur-
rence. The information obtained may be useful in coun-
seling gravid women regarding recurrence risk, as well as
in identifying high-risk populations.
Protocol Subcommittee: Robert L. Goldenberg, MD
(Chair), Brian M. Mercer, MD, Atef H. Moawad, MD, Jay
D. Iams, MD, Paul J. Meis, MD, Rachel L. Copper, MSN,
Francee Johnson, RN, Anita F. Das, MS, Elizabeth Thom,
PhD, and Donald McNellis, MD.
Participating members of the National Institute of
Child Health and Human Development Maternal-Fetal
Medicine Units Network were as follows: Paul J. Meis.
MD, Eberhard Mueller-Heubach, MD, Melissa Swain,
RN, and Allison Frye, RN, Bowman Gray School of
Medicine; Steve N. Caritis, MD, James H. Harger, MD,
Margaret Cotroneo, RN, and Cynthia Stallings, MSN,
Magee Women’s Hospital, Pittsburgh; Anita F. Das, MS,
Elizabeth A. Thom, PhD, Raymond P. Bain, PhD, Lucy
Leuchtenburg, and Molly Fischer, MPH, CRNP, George
Washington University Biostatistics Coordinating Center;
Donald McNellis, MD, Sumner J. Yaffe, MD, Charlotte
Catz, MD, and Mark Klebanoff, MD, National Institute of
Child Health and Human Development; Jay D. Iams,
MD, Mark B. Landon, MD, Francee Johnson, RN, and
Carol Mueller, RNC, Ohio State University; Gary R.
Thurnau, MD, J. Christopher Carey, MD, and Arlene
Meier, RN, University of Oklahoma; John C. Hauth, MD,
Robert L. Goldenberg, MD, and Rachel L. Copper, MSN,
University of Alabama; Atef H. Moawad, MD, Marshall
Lindheimer, MD, and Phyllis Jones, MPH, RN, University
of Chicago; Menachem Miodovnik, MD, Tariq A. Siddiqi,
MD, and Nancy Elder, MSN, University of Cincinnati; J.
Peter Van Dorsten, MD, M. Kathryn Menard, MD, Roger
B. Newman, MD, Beth A. Collins, PhD, and Faye
LeBoeuf, MSN, University of South Carolina; Baha M.
Sibai, MD, Brian M. Mercer, MD, Risa Ramsey, BSN, and
Joyce Fricke, RNC, University of Tennessee; Sidney F.
Bottoms, MD (deceased), Mitchell P. Dombrowski, MD,
and Gwendolyn S. Norman, MPH, RN, Wayne State
University; and James M. Roberts, MD, Steering
Committee Chairman, University of Pittsburgh.
REFERENCES
1. Robertson PA, Sniderman SH, Laros RK Jr, Cowan R, Heilbron
D, Goldenberg RL, et al. Neonatal morbidity according to gesta-
tional age and birth weight from five tertiary care centers in the
United States, 1983 through 1986. Am J Obstet Gynecol
1992;166:1629-45.
2. Copper RL, Goldenberg RL, Creasy RK, DuBard MB, Davis RO,
Entman SS, et al. A multicenter study of preterm birth weight
and gestational age-specific neonatal mortality. Am J Obstet
Gynecol 1993;168:78-84.
3. Meis PJ, Ernest JM, Moore ML. Causes of low birth weight births
in public and private patients. Am J Obstet Gynecol
1987;156:1165-8.
4. Savitz DA, Blackmore CA, Thorp JM. Epidemiologic characteris-
tics of preterm delivery: etiologic heterogeneity. Am J Obstet
Gynecol 1991;164:467-71.
5. Creasy RK, Gummer BA, Liggins GC. System for predicting
spontaneous preterm birth. Obstet Gynecol 1980;55:692-5.
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Volume 181, Number 5, Part 1
Am J Obstet Gynecol
6. Main DM, Richardson D, Richardson D, Strong S, Weller SC.
Prospective evaluation of a risk scoring system for predicting
preterm delivery in black inner city women. Obstet Gynecol
1987;69:61-6.
7. Mueller-Heubach E, Guzick DS. Evaluation of risk scoring in a
preterm birth prevention study of indigent patients. Am J
Obstet Gynecol 1989;160:829-37.
8. Holbrook RH, Laros RK, Creasy RK. Evaluation of a risk-scoring
system for prediction of preterm labor. Am J Perinatol 1989;6:62-8.
9. Owen J, Goldenberg RL, Davis RO, Kirk KA, Copper RL.
Evaluation of a risk scoring system as a predictor of preterm birth
in an indigent population. Am J Obstet Gynecol 1990;163:873-9.
10. Herron MA, Katz M, Creasy RK. Evaluation of a preterm birth
prevention program: preliminary report. Obstet Gynecol
1982;59:452-6.
11. Bakketeig LS, Hoffman HJ. Epidemiology of preterm birth: re-
sults from a longitudinal study of births in Norway. In: Elder
MG, Hendricks, editors. Preterm labor. London: Butterworth
International Medical Reviews; 1981. p. 17.
12. Bakketeig LS, Hoffman HJ, Harley EE. The tendency to repeat
gestational age and birth weight in successive births. Am J
Obstet Gynecol 1979;135:1086-103.
13. Funderbunk SJ, Guthrie D, Meldrum D. Suboptimal pregnancy
outcome among women with prior abortions and premature
births. Am J Obstet Gynecol 1976;126:55-60.
14. Goldenberg RL, Mayberry SK, Copper RL, Dubard MB, Hauth
JC. Pregnancy outcome following a second-trimester loss.
Obstet Gynecol 1993;81:444-6.
15. Carr-Hill RA, Hall MH. The repetition of spontaneous preterm
labour. Br J Obstet Gynaecol 1985;92:921-8.
16. Hoffman HJ, Bakketeig LS. Risk factors associated with the oc-
currence of preterm birth. Clin Obstet Gynecol 1984;27:539-52.
Mercer et al 1221
17. Goldenberg RL, Iams JD, Mercer BM, Meis PJ, Moawad AH,
Copper RL, et al. The preterm prediction study: the value of
new versus standard risk factors in predicting early and all spon-
taneous preterm birth. Am J Public Health 1997;88:233-8.
18. Meis P, Goldenberg R, Iams J, Mercer B, Moawad A, McNellis D,
et al. The preterm prediction study: significance of vaginal in-
fections. Am J Obstet Gynecol 1995;173:1231-5.
19. Iams J, Goldenberg R, Meis P, Mercer BM, Moawad A, Das A, et
al. The length of the cervix and the risk of spontaneous prema-
ture delivery. N Engl J Med 1996;334:567-72.
20. Mercer BM, Goldenberg RL, Das A, Moawad AH, Iams JD, Meis
PJ, et al. The preterm prediction study: a clinical risk assessment
system. Am J Obstet Gynecol 1996;174:1885-95.
21. Goldenberg RL, Mercer BM, Meis PJ, Copper RL, Das A,
McNellis D. The preterm prediction study: fetal fibronectin test-
ing and spontaneous preterm birth. NICHD Maternal-Fetal
Medicine Units Network. Obstet Gynecol 1996;87:643-8.
22. Iams JD, Goldenberg RL, Mercer BM, Moawad A, Thom E,
Meis PJ, et al. The Preterm Prediction Study: recurrence risk of
spontaneous preterm birth. Am J Obstet Gynecol 1998;178:
1035-40.
23. Hillier SL, Martius J, Krohn M, Kiviat N, Holmes KK,
Eschenbach DA. A case-control study of chorioamniotic infec-
tion and histologic chorioamnionitis in prematurity. N Engl J
Med 1988;319:972-8.
24. Mueller-Heubach E, Rubenstein DN, Shen Schwarz S.
Histologic chorioamnionitis and preterm delivery in different
patient populations. Obstet Gynecol 1990;75:622-6.
25. Watts DH, Krohn MA, Hillier SL, Eschenbach DA. The associa-
tion of occult amniotic fluid infection with gestational age and
neonatal outcome among women in preterm labor. Obstet
Gynecol 1992;79:351-7.
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Editorials represent the opinions of the authors and The Journal and
Prepregnancy Weight and Pregnancy Outcome
In this issue of THE JOURNAL, there are two articles that
describe the relationship between maternal size and a preg-
nancy with a neural tube defect (NTD).1,2 Both investigations
are population-based, case-controlled studies involving more
than 500 NTD cases and controls. Information on maternal
characteristics, including pregnancy events, prepregnancy
weight, and dietary intake, was obtained by in-person inter-
views with each mother within 5 to 6 months of delivery. The
risk of NTD-affected pregnancy was estimated after adjust-
ing for multiple confounders. These two groups of investi-
gators independently reached a similar conclusion: women
who are obese (ie, women who have a body mass index [BMI]
of >29 kg/m2 or body weight of more than 80 kg) at the
beginning of pregnancy are more likely to have infants with
NTDs and this association is independent of folate intake.
Since previous studies have indicated similar relationships,3,4
it is likely that this association will hold up under further
scrutiny.
See also pp 1089 and 1093.
Neural tube defects, malformations of the vertebral col¬
umn, skull, meninges, spinal cord, and brain, are among the
most common major birth defects and have a devastating
effect on patients and their families. During the past several
years, it has been well established that periconceptional folie
acid supplementation reduces the risk of first occurrence or
recurrence of NTD-affected pregnancies5·6; however, the pre¬
ventive effect is not 100%. As many as 30% of the recurrences
of NTD pregnancies are not prevented by periconceptional
folie acid supplementation. The mechanisms ofthe preventive
effect of folie acid on NTDs are unknown.5 Other causes or
precursors of NTDs not relating to folate metabolism are
under investigation. Now, one such factor, maternal obesity,
has been identified.
In addition to NTDs, maternal obesity has been associated
with an increased risk of pregnancy complications and fetal
and neonatal mortality. Maternal obesity coexists with a num¬
ber of medical and behavioral risk factors and is more preva¬
lent in women of low socioeconomic status, itself a risk factor
for poor pregnancy outcome. In a recent review, Abrams and
Parker7 reported that obese women were seven times more
likely to have diabetes, four times more likely to manifest
essential hypertension, and twice as likely to develop preg¬
nancy-induced hypertension than were lean women. In ad¬
dition, during pregnancy, obesity has been shown to be a risk
factor for urinary tract infection, preeclampsia, and cesarean
delivery. Using data from the Collaborative Perinatal Study,
which involved nearly 60 000 women from 1959 to 1966, Na-
eye8 reported that perinatal mortality rates progressively
increased from 37 per 1000 deliveries among lean women to
121 per 1000 deliveries among obese women. Early preterm
delivery was responsible for nearly half of this increase, much
of which was associated with acute chorioamnionitis. It is not
From the Departments of Obstetrics and Gynecology (Dr Goldenberg) and Nutri-
tion Sciences (Dr Tamura), School of Medicine, University of Alabama at Birmingham.
Corresponding author: Robert L. Goldenberg, MD, University of Alabama at Bir-
mingham, 618 South 20 St, OHB 560, Birmingham, AL 35233-7333.
Downloaded From: by a University of Cincinnati Libraries User on 10/10/2017
not those of the American Medical Association.
known why obese women in that study had more infection
associated with early preterm deliveries than lean women.
Naeye8 also noted that other factors associated with neonatal
mortality in obese women included major congenital malfor¬
mations, diabetes mellitus, and twin pregnancies.
Balancing these relationships are other data that show that
the mean birth weight of the offspring of obese women is
greater than that of lean women, most likely because of
increased uteroplacental perfusion and elevated maternal blood
glucose levels, and that the risk of early preterm birth is
significantly less among obese women.9,10 The fact that many
studies use different or overlapping definitions for leanness,
normal weight, and obesity makes the relationships difficult
to untangle. Currently, the Institute of Medicine11 uses four
categories for prepregnancy BMI: low, less than 19.8 kg/m2;
moderate, 19.8 to 26.0 kg/m2; high, 26.1 to 29.0 kg/m2; and very-
high, more than 29.0 kg/m2. It would be helpful if future
studies used these categories to facilitate comparisons. In the
meantime, it is not clear if being obese has a worse prognosis
for pregnancy outcome than being lean.
Excessive leanness is associated with its own set of risk fac¬
tors, including cigarette smoking, low socioeconomic status,
and nutritional deprivation. Maternal leanness is also associ¬
ated with lower maternal blood glucose levels, lower blood
pressures, and less plasma volume expansion associated with
pregnancy compared with women of normal weight.1214 Lean
women are more likely to have growth-retarded infants and
preterm or early preterm delivery than women with normal
weight. Subsequently, these early preterm infants are at
great risk for death and long-term handicap.
There are a number of interesting observations relating
pregnancy outcome to various interventions in lean and obese
women. For example, maternal smoking, which has a strong
negative impact on fetal growth, has a much greater effect on
the fetuses of lean women than on fetuses of obese women;
cigarette smoking reduced the mean infant birth weight by
approximately 160 g in lean women, but only by about 80 g
in obese women. Obesity, therefore, seems to protect the
infant against the deleterious effects of maternal smoking on
fetal growth.15 Smoking probably acts to reduce fetal growth
in a number of ways, but certainly acts as a vasoconstrictor.
In fetuses of lean mothers who are served by a decreased
blood supply and are exposed to low levels of glucose as well
as other nutrients, it is not surprising that smoking-induced
vasoconstriction might have a stronger impact on fetal growth.
We have demonstrated that zinc supplementation during
pregnancy has a powerful impact on pregnancy outcome.16 Zinc
supplementation is associated with an increase in birth weight
and head circumference of infants and a nearly significant 50%
reduction in early preterm delivery. All of these effects oc¬
curred only in women having a BMI of less than 26.0 kg/m2,
while zinc supplementation had no impact on fetal growth or
any other outcome in the infants of obese mothers with a BMI
of 26 kg/m2 or more. In the infants of the leanest mothers with
a BMI of 19.8 kg/m2 or less, zinc supplementation was asso¬
ciated with a 425-g increase in birth weight, reaching a birth
weight nearly similar to the infants of obese mothers.
Furthermore, we have shown that the administration of
low-dose aspirin (60 mg/d) during pregnancy, which has an
enhancing effect on fetal growth probably through a decrease
 RETURN TO TABLE OF CONTENTS
in thromboxane production and an increase in uteroplacental
perfusion, affects fetal growth only in the mothers who were
short or lean.17 The administration of low-dose aspirin had no
effect on the size of the infants when the mothers, BMIs were
higher than the median study population BMI of 22.9 kg/m2.
Therefore, the fact that folie acid appeared protective against
NTD-affected pregnancies in women who were lean but not
in women who were obese as reported by Shaw et al1 and
Werler et al2 is not surprising, although the basis for this
relationship remains unexplained.
Given this array of confusing data, how do we explain the
relationship between maternal prepregnancy weight and preg¬
nancy outcome? First, it is quite clear that women who are
obese have more risk factors than women who are lean or of
normal weight, which leads to higher maternal and perinatal
morbidity and mortality. It is also possible that obese women
have an innate metabolic abnormality or that unmeasured
nutritional factors play a role. Lean women also tend to have
an increase in poor pregnancy outcomes. It is relatively easy
to picture an underperfused, undernourished, and undergrown
fetus at increased risk for preterm delivery and other types of
poor pregnancy outcome. Therefore, it is not surprising that an
increase in fetal growth by zinc supplementation or aspirin
administration occurs predominately in lean mothers.16,17
Considering the recent increase of obesity in the US popu¬
lation and the increased risk of an NTD pregnancy in obese
women, the findings presented in this issue of The JOURNAL
may have important implications for the prevention of NTDs.
At the present time, however, we can only guess at the
possible mechanisms explaining why folie acid supplementa¬
tion in the periconceptional period reduces incomplete clo¬
sure of the neural tube at around 4 weeks' gestation in lean
but not obese women and why obesity itself is a risk factor
for NTDs. Folie acid, even in large quantities, may not be able
to overcome other yet unknown factors that may be associ¬
ated with an increase in NTDs in obese women. For example,
we know that, despite zinc intake being greater, plasma zinc
levels in obese individuals are lower,18 at least in part because
obese women have lower levels of plasma albumin (the major
carrier of zinc in circulation) than lean women.19 This in turn
may reduce the supply of this essential trace mineral to the
uteroplacental unit in early pregnancy. Although no direct
association of inadequate zinc nutriture and NTD pregnan¬
cies has been documented in humans, firm evidence is avail¬
able indicating that malformations of the central nervous
system are common in the offspring of zinc-deficient pregnant
animals.20
Dietary Calcium and Lower Blood Pressure
We Can All Benefit
Dietary calcium intake fails to meet recommended levels in
virtually all categories of Americans.1,2 The health implica-
tions of this trend were recently addressed by a National
Institutes of Health Consensus Conference,2 which noted
that several other common medical conditions besides osteo-
porosis are associated with low dietary calcium intake. The
From the Division of Nephrology, Hypertension, and Clinical Pharmacology, De-
partment of Medicine, Oregon Health Sciences University, Portland.
Reprints: David A. McCarron, MD, Division of Nephrology, Hypertension, and
Clinical Pharmacology, Department of Medicine, Oregon Health Sciences University,
PP Suite 262, 3314 SW US Veterans Hospital Rd, Portland OR 97201-2940.
Downloaded From: by a University of Cincinnati Libraries User on 10/10/2017
In conclusion, the relationships between maternal weight,
whether too low or too high, and interventions aimed at
improving pregnancy outcome are extremely complicated.
Further studies are warranted to investigate the mechanistic
relationships among various nutrients, maternal body size,
and NTD pregnancies. In the mean time, supplementing the
diet of pregnant or soon-to-be pregnant women with both
folie acid and zinc as is now commonly practiced seems to be
a safe and appropriate intervention.
Robert L. Goldenberg, MD
Tsunenobu Tamura, MD
This work was supported in part by Agency for Health Care Policy and Re¬
search contract DHHS 282-92-0055.
1. Shaw GM, Velie EM, Schaffer D. Risk of neural tube defect-affected pregnancies
among obese women. JAMA. 1996;275:1093-1096.
2. Werler MM, Louik C, Shapiro S, Mitchell AA. Prepregnant weight in relation to
risk of neural tube defects. JAMA. 1996;275:1089-1092.
3. Waller DK, Mills JL, Simpson JL, et al. Are obese women at higher risk for pro-
ducing malformed offspring? Am J Obstet Gynecol. 1994;170:541-548.
4. Watkins M, Scanlon K, Mulinare J, Khoury M. Is maternal obesity a risk factor
for anencephaly and spina bifida? Am J Epidemiol. 1994;139:S11.
5. MRC Vitamin Study Research Group. Prevention of neural tube defects: results
of the Medical Research Council Vitamin Study. Lancet. 1991;338:131-137.
6. Czeizel AE, Dudas I. Prevention of the first occurrence of neural-tube defects by
periconceptional vitamin supplementation. N Engl J Med. 1992;327:1832-1835.
7. Abrams B, Parker J. Overweight and pregnancy complications. Int J Obesity.
1988;12:293-303.
8. Naeye RL. Maternal body weight and pregnancy outcome. Am J Clin Nutr.
1990;52:273-279.
9. Wen SW, Goldenberg RL, Cutter GR, Hoffman HJ, Cliver SP. Intrauterine
growth retardation and preterm delivery: prenatal risk factors in an indigent popu-
lation. Am J Obstet Gynecol. 1990;162:213-218.
10. Owen J, Goldenberg RL, Davis RO, Kirk KA, Copper RL. Evaluation of a risk
scoring system as a predictor of preterm birth in an indigent population. Am J Ob-
stet Gynecol. 1990;163:873-879.
11. Institute of Medicine. Nutrition During Pregnancy. Washington, DC: National
Academy Press; 1990:9-12.
12. Rosso P, Donoso E, Braun S, Espinoza R, Salas SP. Hemodynamic changes in
underweight pregnant women. Obstet Gynecol. 1992;79:908-912.
13. Naeye RL. Maternal blood pressure and fetal growth. Am J Obstet Gynecol.
1981;141:780-787.
14. Goldenberg RL, Cliver SP, Cutter GR, Davis RO, Hoffman HJ, Wen SW. Blood
pressure, growth retardation, and preterm delivery. Int J Technol Assess Health
Care. 1992;8(suppl 1):82-90.
15. Cliver SP, Goldenberg RL, Cutter GR, Hoffman HJ, Davis RO, Nelson KG. The
effect of cigarette smoking on neonatal anthropometric measurements. Obstet
Gynecol. 1995;85:625-630.
16. Goldenberg RL, Tamura T, Neggers Y, et al. The effect of zinc supplementation
on pregnancy outcome. JAMA. 1995;274:463-468.
17. Goldenberg RL, Hauth JC, DuBard MB, Copper RL, Cutter GR. Fetal growth
in women using low-dose aspirin for the prevention of preeclampsia: effect of mater-
nal size. J Maternal Fetal Med. 1995;4:218-224.
18. Atkinson RL, Dahms WT, Bray GA, Jacob R, Sandstead HH. Plasma zinc and
copper in obesity and after intestinal bypass. Ann Intern Med. 1978;89:491-493.
19. Maher JE III, Goldenberg RL, Tamura T, Cliver SP, Johnston KE, Hoffman HJ.
Indicators of maternal nutritional status and birth weight in term deliveries. Obstet
Gynecol. 1993;81:165-169.
20. Tamura T, Goldenberg RL. Zinc nutriture and pregnancy outcome. Nutr Res.
1996;16:139-181.
articles by Bucher et al3,4 in this issue and the April 3 issue
of The Journal focus on one of these conditions: increased
arterial pressure. These meta-analyses of randomized con-
trolled trials of blood pressure and calcium levels in 2412
See also p 1113 and p 1016 in the April 3, 1996, issue.
adults and in 2459 pregnant women provide compelling evi-
dence that both normotensive and hypertensive individuals
may experience reductions in blood pressure when calcium
intake is increased.
Journal of Midwifery & Women’s Health www.jmwh.org
Original Review RETURN TO TABLE OF CONTENTS

Racial Discrimination and the Black-White Gap

in Adverse Birth Outcomes: A Review
Carmen Giurgescu, PhD, WHNP, Barbara L. McFarlin, CNM, PhD, RDMS, Jeneen Lomax, CNM, APN,
Cindy Craddock, RNC-OB, WHNP, Amy Albrecht, CNM, APN

Introduction: The purpose of this integrative review was to evaluate what is known about the relationship between racial discrimination and
adverse birth outcomes.
Methods: A search of the Cumulative Index of Nursing and Allied Health Literature, MEDLINE, and PsycINFO was conducted. The keywords
used were: preterm birth, premature birth, preterm delivery, preterm labor, low birth weight, very low birth weight, racism, racial discrimination,
and prejudice. Ten research studies were reviewed. All of the studies included African American women in their samples, were conducted in
the United States, and were written in English. We did not limit the year of publication for the studies. Data were extracted based on the birth
outcomes of preterm birth, low birth weight, or very low birth weight.
Results: A consistent positive relationship existed between perceptions of racial discrimination and preterm birth, low birth weight, and very low
birth weight. No relationship was found between racial discrimination and gestational age at birth.
Discussion: Future research should explore the effects of racial discrimination as a chronic stressor contributing to the persistent gap in birth
outcomes between racial groups.
J Midwifery Womens Health 2011;56:362–370  c 2011 by the American College of Nurse-Midwives.

Keywords: gestational age at birth, low birth weight, preterm birth, racial discrimination, racism, health status disparities

INTRODUCTION and a number of factors, including socioeconomic status,6 ed-

Despite modern technology and numerous efforts to improve
birth outcomes, rates of preterm birth and low birth weight
(LBW) have increased in the United States. Between 1990 and
2007, preterm birth rates increased by 21%, and LBW rates
increased by 19%.1 In 2007, 12.7% of neonates in the United
States were born prematurely (⬍ 37 completed weeks’ gesta-
tion), and 8.2% of neonates were born with LBW (⬍ 2500 g).1
Preterm birth and LBW are 2 of the leading causes of in-
fant mortality.2 In 2007, 6.77 of 1000 infants died during the
first year of life.3 Preterm birth and LBW also have been as-
sociated with pediatric health problems such as respiratory
distress syndrome; vision, hearing, immunologic, neurologic,
and digestive issues; cerebral palsy; and delayed brain func-
tion.1 Compromised fetal development may affect cognitive
development and overall health throughout the child’s life.4
One of the major predictive risk factors for adverse birth
outcomes in the United States is being African American.5
Since 1940, a disparity in infant mortality between the African
American and non-Hispanic white populations has been
documented.2 Compared with non-Hispanic white women,
African American women are more likely to have preterm
births (11.5% and 18.3%, respectively), LBW neonates (7.2%
and 13.8%, respectively),1 and infants who die before the first
year of life (5.73/1000 live births and 12.92/1000 live births,
respectively).3 Researchers have examined multiple contrib-
utors to adverse birth outcomes yet have failed to explain
all of the contributors influencing the racial gap. There are
demonstrated relationships between adverse birth outcomes
Address correspondence to Barbara L. McFarlin, CNM, PhD, RDMS,
FACNM, University of Illinois College of Nursing, Room 858, 845 S
Damen Ave M/C 802, Chicago, IL 60612. E-mail: bmcfar1@uic.edu
ucation,7 maternal health behaviors,8 prenatal care,9–11 social
support,12 spirituality,9 and stress.13,14 However, these factors
do not account for all of the noted disparities in birth out-
comes.15,16
One hypothesis that could explain this gap is that
African American women experience higher lifetime ex-
posure to chronic stressors, which increases their risk for
poor pregnancy outcomes.17,18 Chronic social stressors in the
everyday life of many African American women, potentially
mediated through the weathering of racism and racial dis-
crimination,16 may, over time, cause physiological wear and
tear on the body (known as allostatic load).16 Disparities
in birth outcomes may be due to cumulative exposure to
allostatic load over the course of the woman’s life.
Racial discrimination is a unique psychosocial stressor
that can influence the lives of African American women.10
Compared with pregnant non-Hispanic white women, preg-
nant African American women experience more racial dis-
crimination.10,19 Racial discrimination has been linked to
stress in the African American population20 and in pregnant
African American women specifically.21 Stress levels experi-
enced by pregnant women are related to preterm birth4 and
LBW.22 Thus, racial discrimination, acting as a chronic stres-
sor,23 may potentially predispose African American women to
an increased risk of adverse birth outcomes (eg, preterm birth
and LBW).
We recognize that other racial or ethnic groups may expe-
rience discrimination. However, the purpose of this integra-
tive literature review was to determine what is known about
the relationship between racial discrimination and adverse
birth outcomes for African American women only. For the
purpose of this article, we defined adverse birth outcomes as
preterm birth, LBW, and very low birth weight (VLBW).

362 1526-9523/09/$36.00 doi:10.1111/j.1542-2011.2011.00034.x 

c 2011 by the American College of Nurse-Midwives
 RETURN TO TABLE OF CONTENTS
Background and Definitions
The theoretical framework of this review is based on the the-
ory of allostatic load, developed by McEwen.24 The theory of
allostatic load describes acute stress as an adaptive process,
whereas chronic stress is described as a maladaptive process.
Stress causes a cascade of physiological events, which, in the
acute phase, are adaptive. Allostasis, the adaptive process used
to maintain the stability of an organism, is maintained by an
imperative balance between the sympathetic and parasympa-
thetic nervous systems. Constant insults or threats to the hu-
man body create disequilibrium. This imbalance is referred
to as allostatic load, which subsequently affects health out-
comes.25 We hypothesize that persistent encounters of racial
discrimination experienced by African American women may
lead to an allostatic overload as a result of chronic stress.
Preterm birth and LBW may be potential outcomes of allo-
static overload.
Key terms that formed the basis for this review were
defined as follows: preterm birth, also known as preterm
delivery and premature birth, is the birth of a neonate before
the completion of 37 weeks’ gestation.26 Preterm labor is “the
onset of labor before completion of 37 weeks’ gestation.”26
Low birth weight is a birth weight of less than 2500 g, and
VLBW is a birth weight of less than 1500 g, regardless of
gestational age.26
Racism is the “assignment to racial groups based on phys-
ical characteristics; associated inferiority or superiority of
designated racial groups; hereditary origins of racial groups;
and definition of the group usually determined by the group
in power.”27 Jones28 notes that it is more useful to exam-
ine racism as a social construct that “captures the impact of
racism,” rather than a biological construct reflecting “innate
differences” between races.28 She further hypothesizes that 3
levels of racism exist: institutionalized, personally mediated,
and internalized.28 Institutionalized racism is defined as “dif-
ferential access to goods, services and opportunities of soci-
ety by race.”28 Personally mediated racism is “prejudice and
discrimination, where prejudice means differential assump-
tions about the abilities, motives, and intentions of others”
by race.28 This type of racism can be demonstrated by avoid-
ance, lack of respect, suspicion, scapegoating, and devalua-
tion. Internalized racism is acceptance of negative messages
about own abilities and worth.28 Prejudice is “an irrational at-
titude of hostility directed against an individual, a group, a
race, or their supposed characteristics.”29 Discrimination has
been defined as the “process by which a member, or mem-
bers, of a socially defined group is, or are, treated differently
because of his/her/their membership of that group.”30
METHODS
For the literature review, we used the method set forth by
Whittemore and Knafl.31 A search of the databases Cumu-
lative Index of Nursing and Allied Health Literature, MED-
LINE, and PsycINFO was conducted by using the following
search terms: preterm birth, premature birth, preterm deliv-
ery, preterm labor, low birth weight, very low birth weight,
racism, racial discrimination, and prejudice. We limited the
results to English language and research studies but did not
limit the years of publication. We excluded articles if they
Journal of Midwifery & Women’s Health r www.jmwh.org
had participants who were from non-African American/black
populations or who resided outside the United States. Each of
the 10 articles was reviewed by 2 of the authors to construct
Table 1 and develop an understanding of the results.
RESULTS
Ten research studies were included in this review (Table 1).
Some of the studies measured racism, others measured racial
discrimination, whereas others used the 2 terms interchange-
ably. None of the studies measured prejudice. The studies were
published between 1996 and 2009.
Design
All 10 studies used quantitative designs. Eight of the studies
were prospective,10,14,19,21,32–35 and 2 were retrospective.12,36
All of the studies used nonprobability sampling.
Sample Characteristics
All of the study participants were English-speaking, United
States residents who had singleton pregnancies. The percent-
age of African American (non-African born) participants
ranged from 30%34 to 100%12,21,32,35,36 among the studies.
The sample size ranged from 8512 to 4966 participants.35 Par-
ticipants’ ages ranged from 16 to 44 years; however, some of
the studies did not provide an age range for the sample.12,36 In-
comes covered a broad range among studies and sample pop-
ulations. In 1 study,12 every participant’s yearly family income
was less than $11,000, whereas in another,21 the median fam-
ily income ranged from $18,000 to $24,000 per year.
Measurement
Various data collection instruments were used to assess racial
discrimination. Five10,12,19,33,36 of the 10 studies used the
Krieger37 racial and gender discrimination scale to measure
racial discrimination or items from the scale. Two items from
the Krieger37 scale pertain to unfair treatment, and 6 items ask
about experiences of racial discrimination in 6 situations: at
school, getting a job, at work, getting housing, getting medical
care, and from the police or in the courts. Dominguez et al33
modified the Krieger scale to assess racism exposure across
general life domains (“as a child,” “as an adult”). None of the
studies that used the Krieger instrument stated a Cronbach ␣
for their samples.
One study21 used the Perceptions of Racism Scale,38 a
20-item questionnaire that measures perceived racism and
was developed through interviews with childbearing African
American women related to pregnancy, health care, and race.
The Cronbach ␣ for the study was .91.21
The remaining studies included in this review used dif-
ferent scales. Dailey32 used the Everyday Discrimination Scale
developed by Forman, Williams, and Jackson.39 The Everyday
Discrimination Scale consists of 9 items designed to measure
the presence, frequency, and sources of chronic and routine
experiences of race-related discrimination.32 The Cronbach ␣
for this study was .86.32 Rosenberg et al35 used 9 questions re-
garding experiences of discrimination: they used 3 questions,
which were developed by Williams,40 about unfair treatment;
5 questions about the frequency in daily life of other people’s
363
364
Table 1. Racial Discrimination and the Black-White Gap in Adverse Birth Outcomes: Review of Studies
Author, Year, Instruments/Measurement

Setting Question/Purpose Design/Sample Racial Discrimination Results/Comments

Collins, David, Handler, Wall, &
Andes (2004), Chicago, IL
Collins, David, Symons, Handler,
Wall, & Dwyer (2000),
Chicago, IL
Is there an association between
exposure to interpersonal
racism over a lifetime and
birth outcomes of AA women?
To determine the relationship
between VLBW and the
mother’s perception of being
exposed to racial
discrimination during the
Case-control Krieger racial & gender Studied 5 domains: at work, getting a job, at school, getting medical care,
N = 312 AAa discrimination scale37 and getting service at a restaurant or store.
women McNeilly perceived racism Lifetime exposure to interpersonal racism:
n1 = 104 VLBWb scale48 1 or more domains: ORd for VLBW 1.9 (95% CI, 1.2-3.1)
and preterm Within 72 hours of NICU 3 or more domains: OR for VLBW 3.2 (95% CI, 1.5-6.6)
n2 = 208 normal birth weight admission. Multivariate analysis for independent association of lifetime exposure to
66% received interpersonal racism (maternal age, education, cigarette smoking
Medicaid included in the logistic model):
1 or more domains: OR for VLBW 1.7 (95% CI, 1.0-9.2)
3 or more domains: OR for VLBW 2.6 (95% CI, 1.2-5.3)
Racism experienced during pregnancy:
No association with increased rates of VLBW
Reliability of racism and discrimination scales not reported. Recall bias
could influence results. Interviewers were blinded to study hypotheses.
Case control Krieger racial and gender Racism experienced during pregnancy:
N = 85 AA women discrimination scale37 OR for VLBW 1.9 (95% CI, 0.5-6.6)
n1 = 25 VLBW Within 72 hours of NICU Maternal perception of racial discrimination during pregnancy had an OR
n2 = 60 normal birth weight admission of 4.4 (95% CI, 1.1-18) for VLBW among mothers who had: high parity, late
100% received Medicaid prenatal care, or inadequate social support or who used cigarettes, alcohol, or
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Dailey (2009), California
pregnancy
To broaden knowledge of
predictors of neonate birth
weight in AA people by
examining stress and resource
factors
Prospective cohort
N = 108 pregnant AA women
attending public funded health
clinic 14% infants ⬍ 2500 g
Everyday Discrimination Scale39
Administered during prenatal
appointment Cronbach ␣ =
.86
illicit drugs. Adjusted model for these factors OR 3.3 (95% CI, 0.9-11.3).
Reliability of discrimination scale not reported.
Limitations: small sample size and retrospective design may not have captured
earlier experiences of discrimination.
No correlations between discrimination due to race and infant birth weight.
Tobacco use, number of prenatal visits, and discrimination due to age and
physical disability were significant predictors of infant birth weight
(R 2 = .25; P ≤ .001).
Race (56%) and sex (44%) discrimination cited by participants.
Findings suggest that the experience and effects of discrimination are
multidimensional.

Continued

Volume 56, No. 4, July/August 2011

 Table 1. Racial Discrimination and the Black-White Gap in Adverse Birth Outcomes: Review of Studies
Author, Year,
Setting
Dole, Savitz, Siega-Riz,
Hertz-Picciotto, McMahon, &
Buekens (2004), North
Carolina
Dominguez, Dunkel-Schetter,
Glynn, Hobel, & Sandman
Journal of Midwifery & Women’s Health r www.jmwh.org
(2008), Los Angeles, CA
Korte (1999), Pittsburgh, PA
Murrell (1996), Bay area,
California
365
Question/Purpose
To assess the association between Prospective cohort
psychosocial factors and
preterm birth, stratified by
race
To examine the roles of
stress—general, pregnancy,
and racism—on birth weight
and gestation age in AA
women
To evaluate psychosocial stress
and racial discrimination and
its relationship to weight for
gestational
age and gestational age at
delivery
To examine the relationship of
stress, self-esteem, and racism
to LBW and gestational age in
AA women
Design/Sample
N = 1898 women (n = 724 AA)
University clinic and public
health clinic
AA: 12% PTB
White: 11.5% PTB
Prospective, repeated-measures
design
N = 124 women (n = 51 AA)
recruited at ⬍ 18 wk
pregnancy from clinic and
private practices
AA: 18% PTB, 10% LBW
White: 3% PTB, 1% LBW
Prospective cohort
N = 369 women (47% AA)
Prospective cohort
N = 147 AA women, large HMO,
majority had health insurance
Instruments/Measurement
Racial Discrimination
Items from Krieger racial and
gender discrimination scale37
Administered at 24-29 wk
gestation
Items from racial and gender
discrimination scale37
Composite score (yes/no) created No significant relationship between racial discrimination and weight for
for the study to assess
experiences of discrimination
in 6 situations (school, job
search, medical care, work,
housing, & police/court).
21,38
Perceptions of Racism Scale
Cronbach ␣ = .91
Results/Comments
AA women were at a higher risk of PTB if they reported racial discrimination.
RRb = 1.8 (95% CI, 1.1-2.9).
Large study. No reliability of the modified scale reported. Many
psychosocial variables were studied without multivariate analysis to determine
whether racial discrimination was an independent factor associated with
preterm birth.
Perceived lifetime racism was a predictor of birth weight (P ⬍ .05). Each
unit increase in lifetime perceived racism was associated with a 39.6 g decrease
in birth weight.
Childhood-direct racism was a marginal predictor of birth weight (P ⬍ .10). Each
unit increase associated with 137-g increase in birth weight.
Childhood vicarious racism was a significant predictor of birth weight (P ⬍ .01).
Each unit increase associated with 168-g decrease in birth weight.
Gestational age at birth not related to perceived racism.
Perceived racism significantly correlated with stressful life events (P ⬍ .001),
perceived stress (P ⬍ .001), and state anxiety (P ⬍ .001).
Smokers and drug users excluded from study. Krieger scale was modified;
no reliability of the modified scale reported.
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gestational age; Adjusted OR -0.04 (95% CI, -0.21-0.12).
No significant relationship between racial discrimination and gestational age at
birth; Adjusted OR -3.5 (95% CI, -8.1-1.2).
Doctoral dissertation never published. Racial discrimination score validity
or reliability testing not reported.
No significant relationship between racism and birth weight or gestational age at
birth.
Racism accounted for 6% of variance in stress. Income accounted for 12%
in birth weight.
Developed and validated perceptions of racism scale in a sample of nonpregnant
women aged 20-80 years.
Continued
366
Table 1. Racial Discrimination and the Black-White Gap in Adverse Birth Outcomes: Review of Studies
Author, Year,
Setting
Mustillo, Krieger, Gunderson,
Sidney, McCreath, & Kiefe
(2004),
Multiple sites: Birmingham, AL;
Chicago, IL; Oakland, CA;
Minneapolis, MN
Rosenberg, Palmer, Wise,
Horton, & Corwin (2002),
Boston, MA;
Multiple sites: 13 states
Shiono, Rauh, Park, Lederman, &
Zuskar (1997),
Chicago, IL; New York, NY
Abbreviations: AA, African American; CI, confidence interval; HMO, health maintenance organization; LBW, low birth weight; NICU, neonatal intensive care unit; OR, odds ratio; PTB, preterm birth; RR, relative risk; VLBW, very low birth weight.
a
OR and CI are significant if the proposed risk factor acts as a significant risk to disease if the odds ratio is greater than 1 and the lower bound of the CI does not go below 1.
b
RR is an estimate of risk of “caseness” in 1 group compared with that in another, also called risk ratio.
c
CARDIA study, Mustillo et al.19
Volume 56, No. 4, July/August 2011
Question/Purpose
To determine whether racial
discrimination, as a
psychosocial stressor, may
increase the risk of preterm
delivery and LBW
To assess the relationship of
perceptions of racial
discrimination to preterm
birth in US black women
To determine whether perceived
racial discrimination is a risk
factor for LBW and an
explanation for the ethnic
group disparities in birth
outcomes
Design/Sample
Longitudinal epidemiological
cohort / Stratified random
sample of women in the
CARDIA studyc who gave
birth between y 7 and 10 of the
study (1992-1995)
N = 352 births (n = 152 AA)
AA: 21% PTB, 9% LBW
White: 10% PTB, 2.5% LBW
Secondary analysis of the Black
Women’s Health Study (n =
64,500) age 21-69 y Majority
had health insurance
N = 4966 births (100% AA)
n = 422 PTB
n = 4544 not PTB
n = 85 VLBW
n = 4597 ≥ 2500 g
Prospective cohort
N = 1150 from 6 clinics in
Chicago and New York City
(n = 346 (30%) AA)
45% receiving Medicaid
Instruments/Measurement
Racial Discrimination
Items from Krieger racial &
gender discrimination scale37
Nine questions regarding
experiences of discrimination
Structured interview about
racial/ethnic discrimination
Results/Comments
Of the AA women who reported lifetime racial discrimination in more than 3
situations, 50% had PTB and 61% had LBW.
AA women reporting racial discrimination in 3 or more situations had an OR for
PTB of 3.05 (95% CI, 1.29-7.24).
AA women reporting racial discrimination in 3 or more situations had an OR for
LBW of 4.98 (95% CI, 1.43-17.39).
When gestational age was added to the model, the OR for LBW decreased to 1.56
(95% CI, 0.32-7.76).
No reliability reported for the racial discrimination instrument. PTB rate
increased about 20% from the time data were collected and reported, making it
difficult to generalize findings to present day.
Women who reported unfair treatment on the job had an adjusted OR for PTB of
1.3 (95% CI, 1.1-1.6) and an unadjusted OR for VLBW of 1.4 (95% CI, 0.8-2.2).
Women who reported that people acted afraid of them at least once a wk had an
OR for PTB of 1.4 (95% CI, 1.0-1.9) and an unadjusted OR for VLBW of 1.2
(95% CI, 0.6-2.6).
Among women with ⬍ 12 y of education, the ORs for PTB were 2.4 (95% CI,
1.2-4.6) for having been treated unfairly in housing, 3.5 (95% CI, 1.6-7.6) for
receiving poorer services at least once a wk, and 3.4 (95% CI, 1.5-7.7) for people
acting as if they were afraid of them. Among women with ≥ 16 y of education,
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the OR for PTB was 1.6 (95% CI, 1.1-2.1) for unfair treatment on the job.
No validity or reliability of discrimination instrument reported. Women were
asked if they had been told the neonate was born 3 or more wk early, which
may lead to potential bias.
Perceived racial discrimination during current pregnancy, physical abuse, anxiety,
depression, and overall dissatisfaction with life did not show a significant
association with birth weight.
Living in public housing associated with an 83-g decrease in birth weight.
Having a stable residence was associated with a 76-g increase in birth weight.
Inter-rater agreement established. No example of questions asked during the
interview.
 RETURN TO TABLE OF CONTENTS
behavior toward the participant; and added 1 question about
how often the participant thinks about her race. Korte14 cre-
ated a composite score to incorporate experiences of racial
discrimination from 6 situations; no reliability of the ques-
tionnaire is reported. Finally, Shiono et al34 define discrimi-
nation as experiences of 1 or more incidents of racial discrim-
ination during pregnancy through a structured interview.
Findings
Preterm Birth
Three of the studies included in our review examined preterm
birth as an outcome measure,10,19,35 and 3 addressed gesta-
tional age at birth.14,21,33 All 3 studies that measured preterm
birth defined it as birth at less than 37 weeks’ gestation.10,19,35
Dole et al10 measured racial discrimination during pregnancy,
whereas Rosenberg et al35 and Mustillo et al19 measured racial
discrimination during a lifetime. These studies reported a sig-
nificant positive relationship between racial discrimination
and preterm birth.10,19,35 Rosenberg et al35 found a 1.3-fold
increased risk for preterm birth for African American women
who reported unfair treatment on the job. Dole et al10 found
a 1.8-fold increased risk for preterm birth for African Ameri-
can women who reported racial discrimination. Furthermore,
Mustillo et al19 found that African American women who re-
ported experiencing racial discrimination in 3 or more situa-
tions had a 3-fold increased risk of preterm birth.
The 3 studies that measured gestational age at birth
did not find a relationship with racial discrimination.14,21,33
Dominguez et al33 measured lifetime and childhood experi-
ences of racial discrimination. Korte14 and Murell21 did not
specify whether racial discrimination questions were targeted
to measure discrimination during pregnancy or during the
lifetime. The results of this review indicate that when re-
searchers were measuring the effects of racial discrimination
on birth outcomes, using preterm birth as a dichotomous vari-
able showed a significant effect, whereas using gestational age
at birth as a continuous variable found no significant relation-
ship.
Three studies10,19,33 that examined the relationship be-
tween racial discrimination and preterm birth or gestational
age at birth used the Krieger37 racial and gender discrim-
ination scale. One study35 that reported small increases in
preterm birth (odds ratio [OR] 1.3; 95% confidence interval
[CI], 1.1-1.6) used their own scale to examine the relation-
ship between discrimination and preterm birth. Murrell21 de-
veloped her own racial discrimination scale by using non-
pregnant African American women. The differences in results
may be due to the inconsistent use of different instruments to
measure racial discrimination.
Other factors that also were related to the incidence of
preterm birth or gestational age at birth were maternal and pa-
ternal educational level,33 income,14 smoking,19 high levels of
sex discrimination, adverse life events, and pregnancy-related
anxiety.10 These factors suggest a multidimensional nature to
the relationship of racial discrimination and preterm birth.
Low Birth Weight
Four studies included in the review examined
LBW/VLBW,12,19,35,36 and 5 studies measured birth weight as
Journal of Midwifery & Women’s Health r www.jmwh.org
a continuous variable.14,21,32–34 All 4 studies that measured
LBW/VLBW found a relationship between racial discrimina-
tion and LBW/VLBW. Mustillo et al19 reported that African
American women who reported experiencing increased
levels of racial discrimination were almost 5 times more likely
to deliver LBW neonates compared with women who did not
report racial discrimination.19 However, when gestational age
at birth was added to the model, the OR for LBW decreased
to 1.56 (95% CI, 0.32-7.76). These results may suggest that
the effects of racial discrimination on LBW may be mediated
by gestational age at birth.
All 3 studies12,35,36 that addressed VLBW showed a pos-
itive relationship between racial discrimination and VLBW.
Collins et al12 found a positive relationship between racial
discrimination experienced in pregnancy and VLBW. A later
study by Collins et al36 reported a positive relationship be-
tween VLBW and racial discrimination experienced through-
out the participants’ lives and not merely during pregnancy.36
Rosenberg et al35 found that life experiences of unfair treat-
ment on the job and people being afraid of them were related
to VLBW.
Of the 5 studies14,21,32–34 that examined the relationship
between racial discrimination and birth weight, only that of
Dominguez et al33 found a significant negative relationship
between birth weight and racial discrimination. Perceived life-
time and childhood-directed racism were predictors of birth
weight.33 Each unit increase in lifetime perceived racism was
associated with an almost 40-g decrease in birth weight.33
Each unit increase in childhood vicarious racism was asso-
ciated with a 168-g decrease in birth weight.33 No relation-
ship was noted between racial discrimination and weight per
gestational age in the other 4 studies.14,21,32,34 The results of
this review indicate that when researchers were measuring
the effects of racial discrimination on birth outcomes, using
LBW/VLBW as a dichotomous variable showed a significant
effect, whereas using birth weight as a continuous variable
may not be a robust indicator of adverse birth outcomes.
Of the 5 studies that found relationships between racial
discrimination and LBW/VLBW or birth weight, 4 measured
lifetime or childhood experiences of racial discrimination.
Lifetime and childhood experiences of racial discrimination
may have a greater impact on birth weight than does racial dis-
crimination reported during pregnancy only, suggesting long-
term exposure.17,18
Factors Influencing the Relationship Between Racial Discrimination and
Birth Outcomes
The reviewed studies reported various factors influencing the
relationship between racial discrimination and preterm birth
or LBW. In the study by Collins et al,36 maternal age and a
higher level of education influenced the relationship between
racial discrimination and VLBW. The association between
racial discrimination and VLBW was stronger among women
aged 20 to 29 years compared with teenagers and women aged
more than 30 years.36 For example, women aged 20 to 24 years
who reported racial discrimination in more than 3 domains
had an OR for VLBW of 10.8 (95% CI, 1.8-63.6).36 The study
domains in this case included exposure to interpersonal dis-
crimination at work, getting a job, at school, getting medical
367
 RETURN TO TABLE OF CONTENTS
care, and getting service at restaurants or stores.36 Rosenberg
et al35 reported that women with less than 12 years of edu-
cation who reported experiencing greater unfair treatment in
housing had an unadjusted OR for preterm birth of 2.4 (95%
CI, 1.2-4.6), and those who reported receiving poorer services
at least once a week had an unadjusted OR for preterm birth of
3.4 (95% CI, 1.5-7.7). Collins et al36 also reported that women
with less than 12 years of education who reported racial dis-
crimination in more than 3 domains had an OR for VLBW of
2.0 (95% CI, 0.4-9.8). Women with more than 16 years of ed-
ucation who reported unfair treatment on the job had an OR
for preterm birth of 1.8 (95% CI, 1.0-3.0).35 Similarly, women
with more than 12 years of education who reported discrim-
ination in more than 3 domains had an OR for VLBW of 7.3
(95% CI, 1.9-28.9).36 These results suggest that maternal age
and level of education may influence the relationship between
racial discrimination and birth outcomes.
Obstetrical and behavioral factors also influenced the re-
lationship between racial discrimination and LBW. Mustillo
et al19 reported that the association between racial discrimi-
nation and LBW was mediated by gestational age. Collins et
al36 reported that women who experienced racial discrimina-
tion in more than 3 domains had a higher risk of VLBW if they
had higher parity (≥ 4), had late or no prenatal care, and used
alcohol or drugs during the pregnancy, compared with women
who did not report racial discrimination. However, Mustillo
et al19 reported that whether or not women smoked, the re-
lationship between racial discrimination and LBW remained
significant.
Women’s social support also may influence the relation-
ship between racial discrimination and LBW. Collins et al12
reported that women who experienced racial discrimination
and had inadequate social support also had a higher risk of
VLBW. However, Mustillo et al19 reported that depressive
symptoms did not influence the relationship between racial
discrimination and LBW.
DISCUSSION
The findings of this review show inconsistencies with re-
gard to the relationship between racial discrimination and
preterm birth, LBW, and VLBW. Among the 10 studies re-
viewed, limitations were noted. Two studies used a retrospec-
tive design.12,36 The limitations of using this type of design
include potential bias in the recall of the participants or bias
with regard to the researchers’ interpretations of the findings.
The study by Korte14 was conducted as dissertation research
and was never published. Studies with nonsignificant findings
often do not get published, thus having the potential to impact
conclusions from systematic reviews.41,42 Several researchers
collected data during the time that the participants were preg-
nant; others completed their data collection after birth. In-
dividual reports of racial discrimination may have been in-
fluenced by the timing of the report and the type of racial
discrimination they experienced. Furthermore, participants’
knowledge of the birth outcome at the time of interview may
have influenced reports of perceived racial discrimination.
The majority of the studies had small sample sizes, and
all used convenience sampling. The sample size ranged from
8512 to 4966,35 and 1 study had only 25 women in the LBW
368
group.12 Two9,21 of the 49,14,21,34 studies that did not show a
relationship between racial discrimination and birth weight
had sample sizes of less than 150. Furthermore, only 47% of
the 369 women participating in the Korte14 study were African
American. According to the Centers for Disease Control and
Prevention,1 13.8% of African American women have LBW
neonates. Therefore, the sample size of these studies9,21 may
not be large enough to have appropriate power for the statis-
tical tests to reach significance for LBW.
Potential bias may have existed in relation to the methods
of data collection used. Self-reported data relies on accurate
recall of relevant data. Various studies used questionnaires,
which Dole et al43 found were most likely to be completed
by women who were married, had more education, and were
white. Other studies obtained data via interviews, which had
potential for intimidation and therefore lower reporting of ex-
periences with racial discrimination.
Researchers used different tools to measure racial dis-
crimination, which may impact the consistency of the find-
ings. Of key concern is the fact that the tools used were not
designed to specifically evaluate the pregnant women. Many
researchers did not report reliability of the instruments for
their samples. The majority of the scales used focused on the
interpersonal forms of racial discrimination and failed to ad-
dress institutional and internalized forms. For that reason, the
scales may fail to capture features of the health care system that
contribute to discrimination in the provision of prenatal care.
Various studies addressed acute experiences of racial discrim-
ination during pregnancy, and others examined chronic ex-
posure to racial discrimination throughout participants’ lives.
These differences in the methodologies used among the stud-
ies to assess experiences of racial discrimination may limit the
ability to compare study results.
Recommendations for Future Research
McEwen’s24 theory of the allostatic load describes acute stress
as an adaptive process, whereas chronic stress is described as a
maladaptive process. We hypothesized that persistent encoun-
ters of racial discrimination experienced by African Ameri-
can women may lead to an allostatic overload as a result of
chronic stress. Preterm birth and LBW may be potential out-
comes of allostatic overload. We recommend that this theory
be used for future research as a framework to examine birth
outcomes related to the impact of lifetime exposure to racial
discrimination.
More sensitive instruments need to be developed
to specifically address racial discrimination experienced
throughout the lifespan. For example, Dominguez et al33
modified the Krieger scale to measure experiences of racial
discrimination “as a child” and “as an adult,” and they found
that childhood experiences of racial discrimination were
related to birth weight. These findings suggest that childhood
and lifetime exposure to racial discrimination can have
profound long-term health effects. In order to examine the
relationship between racial discrimination and preterm birth,
LBW, and VLBW, researchers need to 1) use prospective
designs; 2) have an adequate sample size, with participants
from a broad range of demographics such as low and high
levels of education and income; prenatal care received early,
Volume 56, No. 4, July/August 2011
 RETURN TO TABLE OF CONTENTS
late, or not at all; and residents of urban, rural, and suburban
locations; 3) use reliable instruments to measure racial
discrimination in its various forms; and 4) use data collection
techniques that minimize bias.
Implications for Practice
It has been well-documented that a disparity exists between
African American and non-Hispanic white women with re-
gard to birth outcomes. Although there is insufficient evi-
dence to demonstrate a clear relationship between racial dis-
crimination and birth outcomes, 1 result worth noting is the
consistent positive relationship between racial discrimination
with preterm birth and LBW/VLBW. Health care providers
need to consider reproductive health from the life-course per-
spective because reproductive health may be compromised
well before women become pregnant.16,18 Thus, clinicians
should be aware of various psychosocial factors that may
contribute to an increased risk of preterm birth, LBW, and
VLBW, and they should consider screening all African Amer-
ican women both prior to conception and prenatally to ascer-
tain experiences of racial discrimination. We recommend that
clinicians ask women about their experiences of racial dis-
crimination. Furthermore, the Krieger37 discrimination scale
has been shown to be reliable in other populations,44 even
though the studies included in this review did not report its
reliability. We realize that other racial and ethnic groups may
experience discrimination, but the review included studies of
African American women only. Heightened awareness of an
increased risk for preterm birth and LBW may require in-
creased surveillance for growth restriction, education about
the signs of preterm labor, discussion of the effects of chronic
stress and racism on pregnancy, and suggestions for coping
strategies.
Different strategies may be needed to cope with an acute
episode of racial discrimination versus a lifetime exposure of
maltreatment.45 More effective coping on the individual level
may contribute to a person’s ability to self-regulate in the face
of discrimination.45 Social support such as seeking out and
talking to others may be a means of coping with racial dis-
crimination.46 Providing prenatal care with a group model of
care, such as CenteringPregnancy, may provide an opportu-
nity for more social support than traditional individual care
models. One randomized controlled trial of group prenatal
care compared with individual care found a 33% reduction
in preterm birth (OR 0.67; 95% CI, 0.44-0.99; P = .045).47
African American women in the study experienced an even
greater reduction in preterm birth (OR 0.59; 95% CI, 0.38-
0.92; P = .02).47 Group prenatal care may be an effective strat-
egy to reduce the preterm birth rate, especially with African
American women, and increased social support may be 1
mechanism.
Providing more culturally responsive health care is also
a potential intervention of decreasing health disparities. Tai-
lored interventions that focus on day-to-day experiences of
African American women are needed45 (other groups may ex-
perience racial discrimination; however, this review focused
only on African American women). A greater understand-
ing of the types of support that may be beneficial for differ-
ent dimensions of the experiences of racial discrimination are
needed in order to develop support-based interventions that
Journal of Midwifery & Women’s Health r www.jmwh.org
have the potential to decrease health disparities in preterm
birth.46
CONCLUSION
This integrative literature review offers promising new in-
sights into a long-standing problem of birth outcome dis-
parities. The findings suggest that racial discrimination may
be a potential contributor to the disparity in birth outcomes
between African American women and non-Hispanic white
women. Consistent exposure to racial discrimination, from
childhood to the present, may be a chronic stressor that in-
creases the allostatic load and leads to adverse health out-
comes. Providers should be aware of these potential risk
factors and adjust the assessment of patients who are at
risk.
AUTHORS
Carmen Giurgescu, PhD, RN, WHNP, is an assistant profes-
sor at the University of Illinois College of Nursing in Chicago,
Illinois.
Barbara L. McFarlin, CNM, PhD, RDMS, is an assistant pro-
fessor at the University of Illinois College of Nursing in
Chicago, Illinois.
Jeneen Lomax, CNM, is a certified nurse midwife at the Little
Village Women’s Health in Chicago, Illinois.
Cindy Craddock, WHNP, is a women’s health care nurse prac-
titioner at Hill AFB, United States Air Force.
Any Albrecht, CNM, is a certified nurse midwife at the Lawn-
dale Christian Health Center in Chicago, Illinois.
CONFLICT OF INTEREST
The authors have no conflicts of interest to disclose.
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HHS Public Access

Author manuscript
Ethn Dis. Author manuscript; available in PMC 2015 May 26.
Author Manuscript

Published in final edited form as:

Ethn Dis. 2010 ; 20(1 0 2): S2–62-76.

Closing the Black-White Gap in Birth Outcomes: A Life-course

Approach
Michael C. Lu, MD, MPH, Milton Kotelchuck, PhD, MPH, Vijaya Hogan, DrPH, Loretta Jones,
MA, Kynna Wright, PhD, MPH, and Neal Halfon, MD, MPH
Departments of Obstetrics and Gynecology (MCL) and Pediatrics (NH), David Geffen School of
Medicine at UCLA; the Department of Community Health Sciences and the Center for Healthier
Children, Families and Communities, UCLA School of Public Health (MCL, NH) and Department
Author Manuscript

of Maternal and Child Health, Boston University School of Public Health (MK) and Department of
Maternal and Child Health, University of North Carolina at Chapel Hill (VH) and Healthy African
American Families, Los Angeles, CA (L)) and UCLA School of Nursing (KW)

Abstract
In the United States, Black infants have significantly worse birth outcomes than White infants.
Over the past decades, public health efforts to address these disparities have focused primarily on
increasing access to prenatal care, however, this has not led to closing the gap in birth outcomes.
We propose a 12-point plan to reduce Black-White disparities in birth outcomes using a life-
course approach. The first four points (increase access to interconception care, preconception care,
quality prenatal care, and healthcare throughout the life course) address the needs of African
Author Manuscript

American women for quality healthcare across the lifespan. The next four points (strengthen father
involvement, systems integration, reproductive social capital, and community building) go beyond
individual-level interventions to address enhancing family and community systems that may
influence the health of pregnant women, families, and communities. The last four points (close the
education gap, reduce poverty, support working mothers, and undo racism) move beyond the
biomedical model to address the social and economic inequities that underlie much of health
disparities. Closing the Black-White gap in birth outcomes requires a life course approach which
addresses both early life disadvantages and cumulative allostatic load over the life course.

Keywords
Life Course Perspective; Disparities; Birth Outcomes; Programming; Allostatic Load;
Author Manuscript

Preconception Care; Prenatal Care; Quality; Father Involvement; Systems Integration; Social
Capital; Maternity Leave; Childcare; Racism

In the United States, Black infants are more than twice as likely to die within the first year of
life as a White infant, a gap that has not substantially closed in over half a century.1,2 A
significant portion of the disparity in infant mortality is attributable to the near two-fold
increased rates of low birth weight (LBW) and preterm births, and the near three-fold

Address correspondence or reprint request to: Michael C. Lu, MD, MPH; Department of Community Health Sciences; UCLA School
of Public Health; Box 951772; Los Angeles, CA; 90095-1772; 310-825-5297; 310-794-1805 (fax); mclu@ucla.edu.
 RETURN TO TABLE OF CONTENTS

Lu et al. Page 2

increased rates of very low birth weight (VLBW) and very preterm births, among Black
Author Manuscript

infants.3

The cause of racial disparities remains largely unexplained. Most studies focus on
differential exposures to risk and protective factors during pregnancy, such as maternal
behaviors,4 prenatal care utilization,5 psychosocial stress6 or infections.7 These factors
however do not adequately account for the racial gap in birth outcomes.8,9 Lu and Halfon10
recently proposed an alternative approach to examining racial-ethnic disparities in birth
outcomes using the life course perspective. The life course perspective conceptualizes birth
outcomes as the end product of not only the nine months of pregnancy but the entire life
course of the mother before the pregnancy. Disparities in birth outcomes, therefore, are the
consequences of both differential exposures during pregnancy and differential
developmental trajectories across the life span.
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The life course perspective synthesizes two longitudinal models: an early programming
model and a cumulative pathways model.11,12 The early programming model posits that
early life exposures influence future reproductive potential. For example, perinatal stress is
associated with high stress reactivity that persists into adulthood.13–15,17,18 This, in turn,
may be related to feedback resistance from altered expression of glucocorticoid receptors in
the developing brain.16 Exposure to stress hormones during sensitive periods of immune
maturation in early life may also alter immune function, leading to increased susceptibility
to infectious or inflammatory diseases later in life.19 Hypothetically, maternal stress during
pregnancy could prime fetal neuroendocrine and immune systems with stress hormones,
leading to higher stress reactivity and immune-inflammatory dysregulation that could
increase a female offspring’s vulnerability for preterm labor and LBW later in life. Thus the
increased risk of African American women to preterm birth and LBW may be traced to
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greater exposures to stress hormones during pregnancy, early life, and possibly even in
utero.

The cumulative pathways model proposes that chronic accommodation to stress results in
wear and tear, or allostatic load,20 on the body’s adaptive systems, leading to declining
health and function over time. Animals and humans subjected to chronic and repeated stress
have elevated basal cortisol levels and exaggerated hypothalamic-pituitary-adrenal (HPA)
response to natural or experimental stressors.21,22 This HPA hyperactivity may reflect the
inability of a worn-out system for self-regulation, possibly due to loss of feedback inhibition
via down-regulation of glucocorticoid receptors in the brain.21 Chronically elevated cortisol
levels may also lead to immune suppression and immune-inflammatory dysregulation.23
HPA hyperactivity and immune-inflammatory dysregulation are two of several possible
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mechanisms by which chronic and repeated stress over the life course may lead to increased
vulnerability to preterm labor caused by stress or infection. This model suggests the
increased risk of African American women for preterm birth and LBW may be related to
increased exposures to stress during pregnancy and possibly to increased weathering of
stress over their life course, resulting in greater allostatic load which may already be present
before pregnancy.24

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Lu et al. Page 3

The life course perspective suggests that closing the Black-White gap in birth outcomes
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requires more than improving access to prenatal care for African American women. From
this perspective, it is not surprising that our national and state policies over the past two
decades have not been more successful in closing the racial gap in birth outcomes. To expect
prenatal care, in less than nine months, to reverse the lifelong, cumulative impact of social
inequality on the health of African American mothers, may be expecting too much of
prenatal care. Closing the racial gap in birth outcomes requires a life course approach,
addressing both early life disadvantages and cumulative allostatic load.

The purpose of this commentary is to propose this life course approach. We recognize we do
not know all life course factors related to the disparities nor have all the answers to address
them, but we believe we must do something. We present a platform of what we can do now
– a 12-point plan building on previous work25 and a literature search for promising
strategies. The 12 points are summarized in Table 1. The goals are to: 1) improve healthcare
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for African American women; 2) strengthen African American families and communities;
and 3) address social and economic inequities that create a disproportionate toll on the
health of African American women over their life course. This plan departs from current
approaches to create a new paradigm for closing the racial/ethnic gap in birth outcomes.
First, it goes beyond prenatal care and addresses healthcare needs of African American
women from preconception to interconception and across the life course. Second, it goes
beyond individual-level interventions and addresses family and community systems. Third,
it goes beyond the medical model and addresses social and economic inequities that underlie
much of health disparities. While a life course approach is needed to address health
disparities in any community, we focus our discussion on its application in the African
American community given the disproportionate burden of infant mortality and other poor
maternal and child health (MCH) outcomes borne by that community.
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Improving Healthcare for African American Women

While health care alone cannot close the gap, it is a good place to start. Health care has a
vital role, especially if provided over the woman’s life course, and not only during
pregnancy. The right health care can promote positive development in early life and reduce
cumulative allostatic load over the life course. Expanding access to interconception care,
preconception care, quality prenatal care, and health care over the life course are important
strategies in closing the racial gap in birth outcomes.

Provide Interconception Care for Women with Prior Adverse Pregnancy Outcomes
Interconception care allows for continuity of health care from one pregnancy to the next.26
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Ideally interconception care should he provided to all women between pregnancies as part of
comprehensive women’s health care. However, given resource constraints, it could be
initially targeted to women with prior adverse pregnancy outcomes (ie, preterm birth, LBW,
intrauterine growth restriction, fetal or infant death). Women with a poor pregnancy
outcome are at substantial risk for having another poor pregnancy outcome.27,28 Many
biobehavioral risk factors for preterm birth are carried from one pregnancy to the next. The
interconception period offers an important window of opportunity for addressing these risk
factors and optimizing women’s health before their next pregnancy. However, present

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Lu et al. Page 4

access to health care in the interconception period is limited for many African American
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women, particularly low-income women whose pregnancy-related Medicaid coverage

generally terminates at sixty days postpartum.26 African American women would benefit
more from interconception programs given their greater risk from prior adverse pregnancy
outcomes and less access to health care during the interconception period.

There have been several interconception care demonstration projects, most notably programs
in Atlanta, Denver, Jacksonville, Philadelphia, and several Healthy Start sites.29,30 Since
2005, Healthy Start programs are required to include an interconception care component.
The interconception care program in Denver was shown to reduce the risk of recurrent LBW
births by one-third, though this finding must be interpreted with caution because of potential
selection bias.

Most interconception programs consist of four components: risk assessment, health

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promotion, medical and psychosocial interventions, and outreach and case management. The
initial risk assessment should be comprehensive to detect factors associated with adverse
birth outcomes, including expert review of medical records. Risk assessment should be on-
going throughout the interconception period, and help guide development of an
individualized care plan for health promotion and medical/psychosocial interventions. Core
services should include family planning,31,32 screening for maternal depression and intimate
partner violence, assessing social support for the pregnant woman, smoking cessation and
substance treatment programs, physical activity and nutritional education and intervention,
management of chronic diseases, and education on back-to-sleep and parenting skills. The
individualized interconception care plan should also address known biobehavioral pathways
to a particular outcome. For example, in preventing recurrent preterm birth, interventions
should consider neuroendocrine, infectious-inflammatory, vascular, and behavioral
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pathways to recurrence.33 Potential strategies may include those that reduce chronic stress
and increase social support,34,35 decrease chronic infections,36,37 restore immune
allostasis,38,39 address vascular causes40 and improve health-promoting behaviors.41
Arguably, many interventions could be adopted on the basis of promoting women’s health
alone, even in the absence of data on their effectiveness in preventing recurrence of adverse
birth outcomes.42,43 The program should be multi-level and include community-level
interventions promoting interconception care.

Interconception care programs could be funded through a Medicaid waiver, expansion of

State Children’s Health Insurance Program (SCHIP) to cover adult family members,
increased scope of services for Title X or state family planning programs, or direct funding
from Title V or non-governmental sources. While more work is needed to explore financing,
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content, and cost-benefit of interconception care, it is an important first step to move us

beyond current focus on prenatal care and toward a more expanded, longitudinally-
integrated approach for addressing disparities in birth outcomes.

Increase Access to Preconception Care for African American Women

As with interconception care, the goal of preconception care is to restore allostasis and
optimize women’s health prior to pregnancy. Many pathophysiologic processes leading to
adverse pregnancy outcomes may have their onset early in pregnancy. For example, an

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Lu et al. Page 5

infection associated with preterm delivery may be present in the urogenital tract before
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pregnancy.43 If it is not cleared by midgestation, preterm labor or preterm premature rupture

of membranes may ensue. Screening for and treating bacterial vaginosis (BV) with
antibiotics during pregnancy may be less effective in preventing preterm birth. This may
partially explain the disappointing results of several antibiotic trials in pregnancy.44,45 Even
if the infection is treated, it may be too late to stop immune-inflammatory processes.
Preconception care provides an important opportunity to treat ongoing infection and restore
immune allostasis. Most models of preconception care were developed with the primary aim
of preventing congenital anomalies.46 Further research is needed to develop preconceprional
strategies for preventing preterm births and LBW by addressing stress reduction, social
support, immune response, chronic infections, inflammation, and behavioral and nutritional
risk factors.

Recruiting women into preconception care programs without a specific intervenable event
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and a targetable time period may be difficult.47 Targeting preconception care to couples
actively planning a pregnancy will miss about half of all live births unintended at
conception.48 Therefore, preconceptional health promotion and disease prevention should be
integrated into a continuum of care throughout the life cycle.48 Every routine visit by any
woman who may become pregnant at some time should be viewed as an opportunity to
provide preconception care.49 Public health efforts should focus on increasing access to,
setting standards for, and assuring quality of preconception care. Since Medicaid covers
about half (51%) of African Americans with family incomes below the poverty level and
17% of those between 100% and 199% of the poverty level (near-poor),50 expanding
Medicaid to cover preconception care could substantially increase access for low-income
African American families. Another 15% of the poor and nearly half (48%) of the near-poor
African Americans have job-based insurance;50 mandating or subsidizing job-based health
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insurance coverage of preconception care could further increase access. These expansions
will still leave out three in ten African American women who are uninsured.50 Strategies
must also consider how to provide preconceptional education and services to adolescents
(eg, school-based clinics or family planning programs). The surest way to increase access to
preconception care is through a national health insurance program which provides coverage
for comprehensive women’s health care.

More work is still needed to explore the financing, standards, and quality assurance for
preconception care. In 2005, the Centers for Disease Control and Prevention (CDC) issued
recommendations to improve preconception health and health care.51 These
recommendations begin to lay out a roadmap toward universal preconception care in the
United States. We believe “preconception care, focusing on women’s overall health … prior
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to pregnancy, will serve as a key component of the next wave of low-birthweight and infant
mortality reduction strategies – and may provide increased savings beyond those
experienced from prenatal care alone.”52 We join the call for this nation to make “a
commitment to advance preconceptional services to a similar extent as it has prenatal
care.”52

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Improve the Quality of Prenatal Care for African American Women

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The life course perspective sees prenatal care as vitally important, both as part of the
continuum of health care for the mother, and as the starting point for the child’s
developmental trajectory. It recognizes the potential contributions of prenatal care to optimal
developmental programming of the baby’s vital organs and systems. For example, poor
glycemic control in mothers with pregestational or gestational diabetes has been linked to
suboptimal fetal development of pancreatic beta-cell structures and functions and greater
adult susceptibility for insulin resistance and diabetes.53 By promoting optimal antenatal
glycemic control, prenatal care may reduce intergenerational transmission of insulin
resistance and diabetes. Thus prenatal care has an important role in closing the racial gap in
not only birth outcomes but possibly in health and developmental outcomes over the life
course and across generations.
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Over the past decade, the racial gap in access to prenatal care has been closing. Today nearly
95% of African American women access prenatal care at some point during pregnancy;
three in four do so in the first trimester.3 However, little has been done to close the racial
gap in the quality of prenatal care. More than one-third of US women reported receiving no
advice on tobacco or other substance use during prenatal care.54 Black women were
significantly less likely than White women to receive health behavior advice from prenatal
care providers, and women who received insufficient health behavior advice were at higher
risk of delivering a LBW infant.54,55 Other studies have documented similar racial gaps in
the quality of prenatal care.56 Quality is also determined by the availability of services.
Many ancillary services (eg, childbirth education classes, mental health or periodontal
services, breastfeeding support), are often unavailable or in short supply in under-resourced
African American communities.
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One promising strategy for improving prenatal care quality is the Breakthrough Series
(BTS), which uses a collaborative learning model and rapid Plan-Do-Study-Act (PDSA)
cycles to bring about quality improvement.57 The effectiveness of the BTS for quality
improvement has been demonstrated in other areas of healthcare,66,67 and is now being
applied to prenatal care through on-going collaboratives in Vermont and Los Angeles.68 The
BTS takes established, but not routinely implemented, clinical standards or best practices
and brings together healthcare providers to examine care processes and make them better
through rapid cycles of change. Already established clinical standards related to prenatal
care include screening and referral for smoking,58 substance use,59 poor nutrition,60 intimate
partner violence,61 and maternal depression,62 just to name a few. More research is needed
to evaluate whether other practices, such as infection screening and treatment (eg,
asymptomatic BV,63 periodontal disease37) or progesterone treatment64,65 can be
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recommended as clinical standards. There is also a need to reconvene a national consensus

meeting on the content of prenatal care, as none has been convened since the mid-1980s.69
Assuring availability of important ancillary services is another important step in prenatal
care quality improvement.

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Expand Healthcare Access over the Life Course for African American Women
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Closing the Black-White gap in birth outcomes requires improving access to quality health
care over the life course. Approximately one in five African American children are
uninsured, and one in four non-elderly African American women are uninsured, rates nearly
twice those for non-Hispanic whites.50 Uninsured African Americans are more than three
times as likely to be without a usual source of care, and more than twice as likely not to have
met minimum standards for physician visits, compared to those with private or Medicaid
coverage.50 Among uninsured African Americans, one in ten aged 0 to 5 years, one in five
aged 6 to 17, and one in five women in fair or poor health fail to meet minimum standards
for regular check-ups.50 The lack of access to preventive and primary care among the
uninsured can cause delayed diagnosis and treatment of chronic diseases (eg, hypertension)
or maintenance of risk behaviors (eg, cigarette smoking, poor nutrition), resulting in a
greater cumulative physiologic toll over the life course and increased biobehavioral
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vulnerability to adverse perinatal outcomes.

Low family incomes are the primary reason for the relative lack of health insurance
coverage among African Americans.50 Medicaid covers only half of African Americans in
poor households, and only 17% of African Americans in near-poor households. Only 16% of
African American women ages 18 to 64 receive Medicaid despite that nearly one-fourth
(23%) are poor and nearly one-half (45%) are near poor. Thus expanding Medicaid coverage
for poor and near-poor families can be an important strategy for increasing healthcare access
for African American women. States have many options, though limited funding, to expand
Title XIX Medicaid coverage for uninsured populations.50 The family coverage option of
section 1931 of the Social Security Act allows states considerable flexibility in setting
income eligibility for Medicaid to cover parents and children above the federal poverty
level. Section 1115 allows states to obtain federal waivers to restructure Medicaid programs
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and enable uninsured adults without children, and families above the current income
eligibility limits, to buy into the program on a sliding scale. African Americans are more
likely to work in settings (ie, large businesses) that provide access to employment-based
health insurance, but they are less likely than Whites in comparable settings to receive such
coverage.50 An employer mandate to cover all employees and their dependents would
substantially close the racial gap in job-based health insurance coverage. But neither
Medicaid expansion nor an employer mandate will provide universal coverage, leaving a
large number of African American women and families still uninsured or under-insured. We
join the call for a national health insurance program to provide universal, comprehensive
coverage to all Americans over their entire lifespan.70

Healthcare access is not all about health insurance. In an increasingly diverse nation, there is
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also need for increased diversity and linguistic and cultural competence in the health
workforce.71–73 Cultural competency and respect for diversity are learned. The work of
healthcare providers increasingly requires communication and interaction with people of
diverse backgrounds. The training ground for acquiring the skills of an effective practitioner
in a diverse society begins in medical, nursing, and other allied health schools, universities,
or earlier. Increased diversity in the faculty and student body of these schools would provide
the level of interaction with diversity necessary to create a culturally competent health

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workforce.74 We support programs and opportunities that increase the diversity of the
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medical workforce.

Strengthening African American Families and Communities

Families and communities can be important sources of support and resiliency, but also
causes of stress and vulnerability, for pregnant women and their children. Being the head of
a single-parent household with little or no father involvement, dealing with fragmented
systems to get unfriendly family support services, living in neighborhoods where neighbors
do not know or look after one another, and residing in communities with concentrated
poverty, high crime rate, poor housing, no parks, limited bus services, and inadequate day
care add to the daily wear and tear many African American mothers experience. Closing the
racial gap in birth outcomes will take more than improving healthcare; it requires
strengthening father involvement, enhancing service coordination and systems integration,
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creating reproductive social capital, and investing in community building and urban renewal.
In short, it will take strengthening family and community support for African American
mothers.

Strengthen Father Involvement in African American Families

Fathers can be a vital source of support for the mother and resiliency for the child. Yet today
many African American men do not stay involved in the pregnancies they caused, not in
raising the children from these pregnancies. In 2006, more than 70% of African American
infants were born to unmarried mothers, up from 22% in 1960.3 Among poor African
American infants, approximately one-third ate born into single-mother families with little or
no father involvement.75 More than half (53%) are born into so-called fragile families.75
While many unmarried fathers may be actively involved at birth, over time their
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involvement declines. Today nearly half (49%) of all poor African American children grow
up in single-mother families with little or no father involvement.75 While father absence is
not unique to the African American community, its toll on African American women and
children is especially high. Studies have shown that, controlling for parental education,
income and other confounding factors, children growing up in father-absent families are at
greater risk for various educational or behavioral problems and poorer developmental
outcomes.80

Father involvement is discussed in detail elsewhere in this issue.76 To strengthen father

involvement in African American families, both an ecological approach81 and a life course
perspective10 are needed. An ecological approach addresses barriers to father involvement at
multiple levels. At the individual level, fathers need educational programs, employment-
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related services, and legal and social services.82 At the interpersonal level, efforts should
focus on improving the relationships between African American men and women, including
marriage counseling, family therapy or skills training in communication and conflict
resolution. At the neighborhood and community level, interventions must address high rates
of unemployment and incarceration among African American. At the institutional level,
many African American churches, universities, and media have taken leadership roles in the
fatherhood movement, but more need to do so.78 These institutions can help promote
changes in norms, values and expectations that support marriage and strengthen the father-

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child bond. Healthcare providers also have an important role in supporting fathers’
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involvement in their family’s healthcare.83

At the policy level, public policy needs to support the ability of fragile families to stay
together. Current policies often do the opposite. Policy reforms are needed to remove
disincentives for father involvement in Temporary Assistance for Needy Families (TANF)
(ie, eliminating the distinction between single- and two-parent families for eligibility),
Earned Income Tax Credit (EITC) (ie. allowing a second-earner deduction), and child
support (eg, establishing amnesty programs or extending TANF, EITC, and other support
services to non-custodial fathers who pay child support).84,85 Most importantly, increasing
economic opportunities by promoting full and consistent employment, job skills training and
retraining, fair trade, and unionization will help restore Black fathers to Black families.77–79

The life course perspective recognizes that fathers have a life history of their own. Their
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involvement in their children’s lives is determined in part by their own life experiences,
including their own father’s involvement in their childhood.76 The capacity to support and
nurture needs to be cultivated over their life course. Thus, closing the Black-White gap in
adverse birth outcomes requires strengthening father involvement through a multi-level
approach addressing individual-level (eg, skills), interpersonal (eg, gender relations),
neighborhood and community (eg, unemployment, incarceration), institutional (eg, cultural
norms, racial stratification), public policy (eg, tax, welfare, and child support), and other life
course factors.

Enhance Systems Coordination and Integration for Family Support Services

Presently there is a great deal of fragmentation in the delivery system for family support
services. Enhancing service coordination and systems integration may help reduce stress and
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increase support for pregnant and parenting women and their families. Women needing
multiple services often have to take time off from work on different days, arrange child care,
find transportation to different appointment locations, fill out duplicative records, and still
may not receive needed services because of missing referral paperwork or provider
miscommunication. Fragmentation in service delivery deters access to care, particularly for
low-income women with other competing needs. These women need help with service
coordination. Programs like the Nurse Family Partnership86 or Black Infant Health
program87 in California have demonstrated some success in providing service coordination
for low-income pregnant and parenting women through case management and home
visitation.

Another possible strategy for service coordination and integration is a family resource center
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with one-stop shopping, which delivers a comprehensive, integrated portfolio of pregnancy

and family support services at a single location or under one organizational umbrella.88 The
Hope Street Family Center in Los Angeles and the Developing Families Center in District of
Columbia offer promising models. Hope Street provides a full array of services, including
prenatal care, well-baby care, primary care, on-site child care, Early Head Start, child
development and family literacy programs. Where it is not possible for all services to occur
under one roof, different providers can work to coordinate services, conduct follow-up upon
referrals, reduce duplication, and create a virtual family resource center.

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To develop a comprehensive, family resource center, a community must be able to knit

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together different categorical programs into an integrated funding mechanism. An on-going

policy experiment, the Monroe County (New York) Child and Family Health Initiative,
works to create an integrated service delivery system driven by family needs rather than
categorical funding requirements.88 This initiative blends funds from six different funding
streams into one master contract with one set of reporting mechanisms and a greater focus
on results. Integration of funding streams may help promote service integration and
multidisciplinary, multi-level, and multisector collaboration. Evaluation of the Monroe
County Initiative is currently ongoing.

Create Reproductive Social Capital in African American Communities

In recent years, social capital has emerged as a possible protective factor against the
detrimental effects of stress on health. Social capital describes the degree of social
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connectedness within a community or society and refers to features of social organization

(eg, networks, norms, social trust) that facilitate coordination and cooperation for mutual
benefit.89,90 Social capital is characterized by: 1) the existence of community networks; 2)
civic engagement; 3) local identity and a sense of solidarity and equity with other
community members; and 4) trust and reciprocal help and support. Several studies link
social capital to health disparities, including disparities in infant mortality.90

A related concept is reproductive social capital – defined as features of social organization

that facilitate coordination and cooperation to promote reproductive health within a
community.91 With respect to pregnancy, it describes the degree of social connectedness of
the pregnant woman to her community. Presently little is known about how to build
reproductive social capital in a community;92 this issue of Ethnicity & Disease provides an
instructive example from a community-based program in Los Angeles.91 One Hundred
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Intentional Acts of Kindness toward a Pregnant Woman was created by Healthy African
American Families to increase reproductive social capital for pregnant women. In local
focus groups, pregnant or postpartum women were asked to identify specific actions that
families, friends, and strangers could take to help make their pregnancies better. From
families and friends, women primarily wanted acts demonstrating emotional and
instrumental support; from strangers they wanted acts of respect for personal space and
common courtesy. Based on their responses, One Hundred Intentional Acts of Kindness
toward a Pregnant Woman was created, printed on fans, and distributed in churches, barber
shops, nail salons, and other locations.

While the effectiveness of the One Hundred Acts program is currently being evaluated, it
provides an example of how a community can create reproductive social capital to increase
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daily social support for pregnant women. The program took on a life course approach as
One Hundred Intentional Acts of Kindness toward a New Mother and One Hundred
Intentional Acts of Kindness to Yourself (for self-support) were also developed. While these
activities do not address structural inequities, they exemplify things a community (under the
leadership of community-or faith-based organizations) can readily do to support pregnant
and parenting women and families.

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Invest in Community Building and Urban Renewal

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As much as it takes a village to raise a child, it takes a community to grow a healthy baby. A
growing body of evidence suggests that neighborhood or community characteristics may be
important determinants of birth outcomes. Increased risk of VLBW births occurred among
African American women rating their neighborhoods unfavorably in eight characteristics:
police protection, property protection, personal safety, friendliness, municipal service
delivery, cleanliness, quietness, and schools.93 Urban African-American women were more
likely to deliver LBW infants when they lived in socioeconomically disadvantaged area,
regardless of individual level poverty and other risk factors.94

Several potential pathways linking neighborhood and community characteristics to adverse

birth outcomes have been suggested. First, because of the history of residential segregation,
African Americans are more likely to live in concentrated poverty neighborhoods where
daily life is more stressful.95 Second, these neighborhoods are more likely to be located near
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freeways, industrial parks, and toxic waste dumps, exposing residents to greater amounts of
pollutants, which increase the risks of adverse birth outcomes.96–100 Third, these
neighborhoods are more likely to include a higher proportion of individuals with
maladaptive coping behaviors, including violence, drug and alcohol abuse, and smoking.
Women living in concentrated poverty neighborhoods are, therefore, more likely to be
exposed to these negative influences. Fourth, there is less access to places to exercise safely
or to purchase fresh fruits and vegetables. In many disadvantaged communities, there are
more liquor stores than grocery stores, and more fast food restaurants than healthy
restaurants. The typical cost of food is approximately 15%– 20% higher in poor
neighborhoods than in affluent neighborhoods, while the quality of food available is
poorer.101 Fifth, these neighborhoods are typically underserved by healthcare and social
service providers.102
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As long as large numbers of African American women grow up and reside in neighborhoods
and communities that put them at early-life disadvantages and under greater cumulative
allostatic load, racial disparities in birth outcomes will likely persist, even with the best
health care. Closing the Black-White gap in birth outcomes requires building stronger and
healthier communities that promote not only healthy pregnancy, but the life course health
development of women and families. Because over half (52%) of all African Americans live
in a central city within a metropolitan area, and nearly 90% live in a metropolitan area, a
good starting place is America’s cities.103 Community building must begin with economic
development; it is difficult to build and sustain a healthy, vibrant community when over half
of its African American male residents are jobless or underemployed, as in many large
cities. Community building also requires infrastructure development, such as affordable and
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decent housing, good schools, safe neighborhood, accessible parks and recreation, clean air
and water, and competent healthcare. The Smart Growth104 and New Urbanism105
movements provide innovative models of urban development that could also promote
population health. And while MCH advocates are not directly in the business of building
housing, schools or parks, they need to partner with those who can.

Community building requires political development. This involves building community

networks and mobilizing civic participation, two important dimensions of social capital. A

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promising model is the Healthy Births Learning Collaboratives (HBLCs) of the Los Angeles
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County Best Babies Network. An HBLC is a network of providers, consumers, researchers,

public health professionals, community leaders, advocates, and other stakeholders whose
primary aim is to improve birth outcomes in their local communities. The collaboration is
guided by the principles of community-based participatory research.106,107 The goal is to
bring MCH and non-MCH partners together on a regular basis for networking and resource
sharing. The HBLC provides a forum for community voices to be heard and creates a
platform for civic engagement, grassroots advocacy, and social and human capital
development by facilitating MCH leadership development and community building.

Address Social and Economic Inequities

Closing the Black-White gap in birth outcomes also requires changing social institutions and
public policies with the goals of reducing early life disadvantages and cumulative allostatic
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load over the life course,108 We believe closing the education gap, reducing poverty,
supporting working mothers and families, and undoing racism are important in eliminating
racial disparities in birth outcomes. This is a new paradigm for MCH partners. Maternal and
child health advocates are not exempt from addressing disparities outside traditional
boundaries; it is imperative that we understand how cumulative social and economic
inequities contribute to health disparities in MCH.

Close the Education Gap

More than 50 years after Brown v Board of Education, the Black-White gap in education
persists. Despite school desegregation, today many of our schools, particularly in inner
cities, remain separate and unequal. The Black-White education gap actually starts before
children enter school. On average, African American children enter kindergarten with
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substantial deficits in reading and math skills, perhaps reflecting early life disadvantages.109
The education gap widens between first and twelfth grades.110 African American children,
particularly from low-income families, are more likely to attend schools with fewer
resources, poorer quality teachers and lower expectations. The gap grows after school and
during summer months, as African American children have fewer opportunities for learning
enrichment outside of school.111 African American children are also more likely to
experience health problems (eg, vision, hearing, oral health, asthma) but less likely to
receive adequate health services for those problems.108 Because of housing and job
instabilities in the family, African American children are more than twice as likely as White
children to have attended at least three different schools by third grade.112 Both health
problems and residential mobility could create stress and interfere with learning. As a result
of all these factors, African American students are significantly less likely to graduate from
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high school and to complete college.103 Lower educational attainment predicts lower
earnings (and less health insurance coverage and access to health care, fewer resources,
greater job strains and insecurity, and poorer housing and neighborhoods). Lower
educational attainment also predicts poorer reproductive health and poorer pregnancy
outcomes,3 possibly mediated through greater cumulative allostatic load over the life course.

The solutions to closing the Black-White gap in birth outcomes require closing the education
gap and are neither easy nor cheap.108 Children cannot learn well without a healthy brain

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and so early childhood development must begin before birth, or even conception. None of us
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are born ready to parent and so parenting education must also begin before the child’s birth.
Presently, most Head Start programs do not begin until age 3 or 4. To narrow the education
gap in early life, children from low-income households should be offered optional full-day,
year-round early childhood programs starting as early as six months of age and full-day,
year-round pre-school at ages 3 and 4. These programs should be staffed with professional
teachers and nurses, and provided curricula emphasizing literacy and appropriate social and
emotional growth. Optimally they should attend K through 12 schools with small class size,
good teachers, high expectations, standards, accountability, after-school and summer
programs, and full-service school-community clinics. The costs of adding these programs to
all US schools with at least 40% low-income children is estimated at $156 billion a year, or
$12,500 per pupil.109 That is the level of commitment our nation must make to close the
Black-White gap in education.
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Reduce Poverty among African American Families

A disproportionate number of African Americans live below the poverty level, accounting
for about one-quarter of the US population in poverty in 2001.103 One in four (25%) Black
women are poor, a rate nearly three times that for non-Hispanic White women (9%). Nearly
one in three (30%) African American children live in a poor household, a rate three times
that for non-Hispanic White children (10%). The poverty rate is highest among single-parent
households headed by African American women; one in three (35%) such households are
poor, and more than half (58%) report an annual income of less than $25,000.103 Poverty
predicts poorer health,108 perhaps reflecting greater cumulative allostatic load over the life
course and resulting in increased biobehavioral vulnerability during pregnancy.

Public policy can help reduce poverty among African American families. First, raising the
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minimum wage, expanding EITC, strengthening collective bargaining, and adopting pay
equity policies will substantially increase incomes for working families. Raising the
minimum wage by one dollar will impact nearly 30% of working African American women
who work for minimum or low wages.113 Expanding EITC may be more effective in
moving families over the poverty line than any other government programs.114 An
innovative proposal, the “Universal Unified Child Credit,” combines both expanded EITC
with child tax credits.115 Unions raise wages and benefits of unionized workers by about
28%.116 Second, investing in a social safety net of programs, such as food stamps, Section 8
vouchers for housing and Medicaid, will help poor African American families meet basic
needs. In 2000, low-income single mothers earned, on average, about $8,000, but after the
EITC and other public assistance their average income nearly doubled, to about $16,000.117
Third, an economy that delivers on full employment, living wages, fair trade, job training
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and retraining, and health insurance coverage will help reduce poverty among African
American families.117

Support Working Mothers and Families

Most African American mothers work. Two areas will serve as examples of where public
policy can better support working mothers: parental leave and child care. Leave policies
give working parents the right to take time off from work without the risk of losing their

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jobs. Before the 1993 Family and Medical Leave Act (FMLA), the United States had no
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national maternity (or paternity) leave legislation,118 in contrast to most developed nations
(most with paid leave). While FMLA dramatically increased both maternity and paternity
leave coverage, it is not universal. Part-time employees, employees in small businesses, and
employees with short job tenure are often not covered or eligible. As a result, only 45% of
parents working in the private sector have guaranteed unpaid parental leave through FMLA.
African Americans have higher coverage under FMLA because they are proportionately
more likely to work in the public sector and for large establishments; nonetheless, nearly
30% of working African Americans parents do not have guaranteed leave. Women with
leave coverage are more likely to take leave and to take longer leaves.118 FMLA is also
limited in that it provides only 12 weeks of unpaid parental leave. Less than 5% of parents
working in the private sector have access to paid parental leave.118 This lack of paid leave is
a barrier to women’s taking leave or taking as much leave as needed; many women face
substantial loss of income by taking an unpaid leave.119 As a result, nearly a third of women
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on maternity leave returned to work in less than 6 weeks; over 70% returned to work in less
than 12 weeks.119

Clearly public policy can do more to support working parents so they can care for their
newborn or sick child without the risk of losing their jobs or pay.118 Some have begun to
call for expanding parental leave coverage, extending the duration of leave allowed,
providing more opportunities for parents of young children to return to work part time, and
making provisions for income replacement during leave.118 With respect to the latter, public
financing options include using: 1) unemployment insurance, 2) temporary disability
insurance programs, 3) a new social insurance program, and 4) a new cash benefit
program.118 In July 2004, California became the first state to provide paid leave for up to six
weeks for parents with a newborn or for employees with an ill family member. Small
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businesses (less than 50 employees) are exempt. The program is funded from employee
payroll tax. In contrast, most European countries provide for longer paid parental leaves
largely financed through social insurance programs.118

One of the most dramatic transformations in the American family over the past 30 years has
been the increased labor force participation rates of mothers with young children.118 The
majority (57%) of mothers with children aged 0 to 3 years work. This trend is particularly
striking for low-income families with single parents. Prior to the 1996 Personal
Responsibility and Work Opportunity Reconciliation Act (PRWORA), Aid to Families with
Dependent Children (AFDC) provided cash assistance to low-income single mothers to
allow them to remain at home and care for their children. The Temporary Assistance for
Needy Families now requires mothers to work or seek employment or training as a condition
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of receiving cash assistance. When single mothers or both parents are working, child care is
needed. In 2001, 48% of African American children aged 0 to 2 years, 74% aged 3 to 6, and
66% in grade school are in non-parental care; the majority in center-based programs.120,121

Two major concerns of working mothers are child care costs and quality. While working
families that pay for child care spend, on average, about 9% of their earnings on child care,
that burden is higher for low-income families (16% of earnings), and for single-parent low-
income families (19% of earnings).122 While low-income families are more likely to receive

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help (eg, relatives, government subsidies) for child care, 40% of low-income families that
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pay for child care spend, on average, $1 of every $6 in earnings for that care.122,123 And
much of the quality of child care available for young children is mediocre or worse.
Children in lower-income families often receive lower quality care than children in higher-
income families.118 Long-term follow-up studies of low-income children randomly assigned
to a treatment group receiving high-quality child care versus a control group without any
special services revealed lower rates of crime, welfare dependency, and teen pregnancy, and
higher educational attainment, employment, and earnings among those receiving high-
quality child care.118,124

Public policy can assist working parents, particularly single mothers and low-income
families, so they can afford high-quality child care.118 Presently, child care for low income
families is supported primarily through subsidies to parents or private market providers.
While this approach increases parental choice, it creates challenges in ensuring access and
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quality. One option is to provide vouchers with a reimbursement rate that increases with the
developmental quality of child care purchased. This would give parents an incentive to seek
higher quality child care and providers an incentive to improve quality. Public early
education programs like Head Start and Early Head Start also need expansion. Head Start is
mostly a part-day, part-year program for poor families, serving about 50% of eligible
children aged 3 or 4 years-old. Early Head Start serves only a small share of eligible
children under 3 years old. These high-quality programs need to be expanded to serve more
children from birth to 5 years old and for more hours to meet the full-day, year-round needs
of working families. Another option is to expand prekindergarten and other early education
programs delivered in community-based child care programs, and to link prekindergarten
funding to higher standards, teacher qualifications, and curriculum requirements. An
Institute of Medicine report estimates that expanding child care subsidies through quality-
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related vouchers for eligible children would cost $54 billion, expanding and increasing
access to full-day, full-year Head Start and Early Head Start would cost $25 billion, and
expanding prekindergarten and other early education programs would cost $25 to $35
billion.118 Despite their high costs, we believe these programs will pay great dividends in
the long run and pay for themselves many times over.

Undo Racism
Increasing evidence suggests racism may be the “cause of the cause” of health disparities in
the United States. The experience of racial discrimination in pregnancy or over the life
course by African American women is associated with increased risk of VLBW
births.125,126 A greater Black-White gap in infant mortality was found in more racially
segregated cities.127,128
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Camara Jones proposed a theoretical framework for understanding racism on 3 levels –

internalized, personally-mediated, and institutionalized racism – and introduced an allegory
about a gardener with 2 flower boxes, with either rich or poor soil, to illustrate the
differences in and remediation of these.129 Institutionalized racism, or differential access to
the goods, services, and opportunities of society by race, is the soil – and this is the most
fundamental level to address for change. Our 12-point plan is essentially about enriching the

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soil with better healthcare, education, child care and other social supports to grow healthier
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mothers and babies.

What are the specific roles of MCH professionals in undoing racism? Maternal and child
health is a field consisting of people from diverse backgrounds and disciplines, including
researchers, service providers, public health professionals, and community advocates. Each
has a role in undoing racism. Researchers need to develop better measures of racism,
identify causal pathways linking racism to health disparities, design longitudinal studies of
both current racism and racism over the life course and across generations, and develop
intervention studies to address multiple levels of racism including institutionalized racism.
Healthcare providers and other service providers need to critically examine their personal
attitudes and behaviors, and institutional practices and policies, to assure all patients or
clients, regardless of race and ethnicity, receive equitable cue.130 Public health professionals
need to make racism a leading public health issue, including collecting data on racism in
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population and community health assessments, assuring equal access to quality healthcare,
monitoring for discriminatory practices, and making policies (or collaborating with other
public agencies to make policies) to assure equal access to goods, services, and opportunities
vital to maternal and child health. In all these efforts, community voices must be heard.
They have been telling us that racism is a main cause of disparities in birth outcomes; now
the community must be included as partners in collaborative efforts to undo racism.

Many of our social institutions and public policies create early life disadvantages and
disproportionate allostatic load on the health of African American women over their
lifespan. We cannot eliminate racial disparities in birth outcomes without addressing racial
disparities in education, healthcare, housing, employment, the criminal justice system and
the built environment. While MCH advocates are not expected to solve all these problems,
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we can do a number of things to address social and economic inequities. First, we need to
educate ourselves about disparities in other domains of life and their impact on maternal and
child health. We need to see how disparities in their fields impact ours and to champion their
causes as much as we need them to champion ours. Second, we need to partner with people
from other walks of life who also address racial disparities. They need to see how disparities
in MCH affect the disparities they address. In too many of our meetings, we are preaching
only to the choir. We can begin by inviting unusual partners from other sectors, such as
education, community development, city planning, and the criminal justice system to our
meetings. Third, we need to join forces with these non-MCH partners in advocacy. All these
require transformative leadership that brings people together to see a common vision and
work for a common cause. The common vision is the life course perspective; the common
cause – social justice.
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Conclusions
We outlined a 12-point plan to close the Black-White gap in birth outcomes using a life
course approach. Collectively these points represent a new approach to an old problem.
They go beyond prenatal care to address the healthcare needs of African American women
over the life course. They go beyond individual-level interventions that are often short-lived
(eg, during pregnancy or a funding grant) to address strengthening family and community

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systems that may have a broader, more lasting impact on the health of pregnant women,
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families, and communities. And they go beyond the biomedical model to address the social
and economic inequities that create disproportionate allostatic load on African American
women’s health.

Two more things are needed for real change – a greater knowledge base and a stronger
political will.131 We need to build on our knowledge base with not only more research, but
better research. Current MCH research is limited by 3 major disconnects: disconnect
between the perinatal period and the rest of the life course (longitudinal disconnect),
disconnect between the individual and her environments (contextual disconnect), and
disconnect across disciplines and between academic and community researchers (intellectual
disconnect). Longitudinal integration is needed to better understand life course influences on
perinatal outcomes and perinatal influences on life course outcomes. This requires more
longitudinal birth cohort studies and databases linkages across the lifespan. Contextual
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integration is needed to better understand influences of neighborhood and community

characteristics on individual health and behaviors, and to delineate how these contextual
factors become embedded in pregnancy physiology and developmental biology (ie, how
social inequality gets under the skin). This requires the development of better measures (eg,
for institutionalized racism) and methodologies for contextual analyses. Intellectual
integration is needed to break out of disciplinary and institutional silos and bridge the
academic-community divide that has limited our research. This requires building
infrastructure (eg, training programs, research networks) to support transdisciplinary
research and community-academic partnerships. Most importantly, we need more praxis –
the integration of knowledge and practice. Research cannot help if it is not translated into
effective interventions. This requires a new approach to designing intervention studies and
evaluating their impact from multi-level, life-course perspectives. It requires collaboration
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among researchers from diverse fields (eg, health, education, housing, criminal justice) and
among hinders to support large-scale social experimentation using a comprehensive, life-
course approach.

We will not close the Black-White gap in birth outcomes without political will to do so.
Political will is the ability to command resources to make things happen (ie, implement the
12 points). There are several things we can do to create political will. First, we need
evaluation research to demonstrate the effectiveness and cost-benefit of these broadened
concepts of health care. The impetus for expanding public coverage of prenatal care in the
late 1980’s came largely from studies demonstrating cost-savings in postnatal infant care
with the provision of prenatal care. Now we need to make an equally compelling case for the
cost-benefit of interconception and preconception care, with benefits measured in terms of
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immediate birth outcomes and long-term health and developmental outcomes, and cost
savings accrued in the healthcare, education, criminal justice, welfare, and other systems.

Second, we need to increase demand for comprehensive women’s health care before and
between pregnancies and over the life course. We must make the case to the American
public that preconception care, interconception care, and access to quality health care over
the lifespan arc as important, if not more than, as prenatal care is to the health and wellbeing

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of mothers and infants. We need to create this demand not just among White middle-class
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women (critical for creating political will), but especially among African American women.

Third, we need leadership. Currently there is growing political will to support father
involvement (eg, federal Fatherhood Initiative) and systems integration (eg, federal
Community Integrated Service System projects). Ideas such as the One Hundred Acts are
met with great receptivity in communities because they demonstrate what communities can
do for themselves to increase social support and social capital for pregnant women and
families. Partisan politics aside, we can all agree that father involvement, family-centered
care, and strong social capital are good for the African American community, or any
community. What we need is leadership to make it happen. Community- and faith-based
organizations can take the lead in creating reproductive social capital. County and state
governments can encourage service integration by blending categorical funding streams.
Maternal and child health professionals can play a leadership role in consensus building –
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bringing people together to sec a common vision and to work on a common cause.

Fourth, we need creativity in building linkages and partnerships. We need linkages to on-
going efforts to address disparities in other domains of life, such as broadening the vision of
No Child Left Behind to include a health component. We need to develop partners from
education, community development, city planning, and the criminal justice system. We need
to make the case to businesses and industries to support more mother-friendly workplaces
and leave policies – in terms of reduced medical costs, lower absenteeism, and a more stable
and productive workforce.

Lastly, we need to renew the public discourse on health disparities in the terms of social
justice. This is primarily a moral issue; in what kind of America do we want our children to
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grow up? An America where a Black baby has twice the chance of dying within the first
year of life as a White baby, three times the chance of being born to a single mother, three
times the chance of growing up in a poor household, twice the chance of going without
health insurance, half the chance of completing college, and a life expectancy 5.5 years
shorter? Or an America where all men and women are created equal and are afforded equal
rights and equal opportunities, and where we treat our fellow Americans as we want to be
treated, or we wish our children to be treated?

Institutionalized racism is often evident as inaction in the face of need. Continuing to do the
same old things that do not work in the face of persisting disparities in birth outcomes
perpetuates institutionalized racism. For too long we have looked for a quick fix to close the
gap. Elimination of racial disparities in birth outcomes is attainable if we make the life
course, perhaps intergenerational, social investments it will take. The 12 points are a
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beginning. The health of our nation tomorrow depends on the choices we make today.

Acknowledgments
Support for this work was provided in pare by the National Institute of Health Women’s Reproductive Health
Career Development fellowship #HD01281-03, the National Institute of Child Health and Development
Community Child Health Network #U01-HD044245, the Centers for Disease Prevention and Health Promotion
Division of Reproductive Health, and the Los Angeles Best Babies Collaborative, a program of First 5 LA. The

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opinions expressed in this paper are the authors’ and do not necessarily reflect the views or policies of the
institutions with which the authors are affiliated.
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Table 1

A 12-point plan to close the Black-White gap in birth outcomes: A life-course approach
Author Manuscript

1 Provide interconception care to women with prior adverse pregnancy outcomes

2 Increase access to preconception care to African American women
3 Improve the quality of prenatal care
4 Expand healthcare access over the life course
5 Strengthen father involvement in African American families
6 Enhance coordination and integration of family support services
7 Create reproductive social capital in African American communities
8 Invest in community building and urban renewal
9 Close the education gap
10 Reduce poverty among African American families
11 Support working mothers and families
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12 Undo racism
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NIH Public Access

Author Manuscript
J Behav Med. Author manuscript; available in PMC 2010 February 14.
Published in final edited form as:
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J Behav Med. 2009 February ; 32(1): 20. doi:10.1007/s10865-008-9185-0.

Discrimination and racial disparities in health: evidence and

needed research

David R. Williams1,2 and Selina A. Mohammed3

David R. Williams: dwilliam@hsph.harvard.edu; Selina A. Mohammed:
1Department of Society, Human Development and Health, Harvard School of Public Health, 677
Huntington Avenue, 6th Floor, Boston, MA 02115, USA
2Departments of African and African American Studies and Sociology, Harvard University,
Cambridge, MA, USA
3 Nursing Program, University of Washington Bothell, Bothell, WA, USA

Abstract
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This paper provides a review and critique of empirical research on perceived discrimination and
health. The patterns of racial disparities in health suggest that there are multiple ways by which racism
can affect health. Perceived discrimination is one such pathway and the paper reviews the published
research on discrimination and health that appeared in PubMed between 2005 and 2007. This recent
research continues to document an inverse association between discrimination and health. This
pattern is now evident in a wider range of contexts and for a broader array of outcomes. Advancing
our understanding of the relationship between perceived discrimination and health will require more
attention to situating discrimination within the context of other health-relevant aspects of racism,
measuring it comprehensively and accurately, assessing its stressful dimensions, and identifying the
mechanisms that link discrimination to health.

Keywords
Racism; Discrimination; Stress; Health disparities; Race; Ethnicity

This paper will provide an overview of the current evidence for and needed research on the
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role of perceived discrimination in health. It seeks to situate the research on personal

experiences of discrimination within the larger literature on racism and health. It begins by
describing some salient patterns in the large and persistent racial/ethnic variations in health
that have provided an impetus to better understand the role of racism in health. It centrally
focuses on recent research on perceived discrimination and health. It critiques the existing
literature with an eye toward highlighting the needed improvements in the conceptualization
and measurement of perceived discrimination that would advance our understanding of the
potential role of race-related stressors in health.

Disparities and the added burden of race

Racial disparities in health in the U.S. are large and pervasive. For most of the 15 leading causes
of death including heart disease, cancer, stroke, diabetes, kidney disease, hypertension, liver
cirrhosis and homicide, African Americans (or blacks) have higher death rates than whites
(Kung et al. 2008). These elevated death rates exist across the life-course with African

Correspondence to: David R. Williams, dwilliam@hsph.harvard.edu.

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Williams and Mohammed Page 2

Americans and American Indians having higher age-specific mortality rates than whites from
birth through the retirement years (Williams 2005). Other data indicate that almost 100,000
black persons die prematurely each year who would not die if there were no racial disparities
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in health (Levine et al. 2001). Another noteworthy characteristic of racial disparities is their
persistence over time. Despite gains in life expectancy for both blacks and whites, the 7 year
racial gap in life expectancy in 1960 was still 5.1 years in 2005 (National Center for Health
Statistics (2007). Similarly, although infant mortality has declined over time for both blacks
and whites, the relative gap between the races is much wider today than it was in 1950 (Williams
and Jackson 2005; NCHS 2007). For some health outcomes, the disparities are worsening.
Trend data for heart disease and cancer—the two leading causes of death in the United States
—indicate that blacks and whites had comparable death rates for these conditions in 1950, but
African Americans now have higher mortality rates than whites (Williams and Jackson 2005;
NCHS 2007).

Research also reveals that pathogenic factors linked to race continue to affect health even when
socioeconomic status (SES) is controlled. In national data there are residual racial differences
in health at every level of SES for multiple indicators of health status, including self-rated
health, heart disease mortality, hypertension and obesity (Pamuk et al. 1998). This pattern exists
for a broad range of other outcomes. A striking example comes from national data on infant
mortality by mothers’ education for all women age 20 years and older. African American
women with a college degree or more education have a higher rate of infant mortality than
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white, Hispanic (or Latino), and Asian and Pacific Islander women who have not completed
high school (Pamuk et al. 1998). Further evidence of the markedly elevated disease risk for
African Americans comes from national data on chronic disease risk factors for blacks, whites
and Hispanics age 40 and over (Crimmins et al. 2007). This study assessed indicators of blood
pressure risk (systolic, diastolic, and pulse rate), inflammation risk (C-reactive protein,
fibrinogen, albumin) and metabolic risk (total cholesterol, HDL cholesterol, BMI and glycated
hemoglobin). A summary indicator of total risk counted how many of these 10 risk factors
were outside of the normal range. This study found that even after adjustment for income,
education, gender and age, blacks had higher scores on blood pressure, inflammation, and total
risk. Importantly, blacks maintained a higher risk profile even after adjusting for health
behaviors (smoking, poor diet, physical activity and access to care).

These data suggest that there are added factors linked to racial status that adversely affect the
health of disadvantaged minority populations in the United States. In seeking to understand
these striking burdens of race, researchers are pursuing three lines of inquiry. First, the
measures of SES are not equivalent across race. For example, compared to whites, college-
educated blacks are more likely to experience unemployment, employed blacks are more likely
to be exposed to occupational hazards and carcinogens even after adjusting for job experience
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and education, blacks have lower wealth at every level of income, and have less purchasing
power because the costs of a broad range of goods and services are higher in Black communities
(Kaufman et al. 1997; Williams and Collins 1995). Second, there is increasing attention to the
need to capture exposure to health risks over the life course. Racial/ethnic differences in
childhood SES and early life psychosocial and economic adversity are likely to be important
contributors to racial disparities in adult health. Third, researchers are exploring the multiple
ways by which racism can adversely affect health (Jones 2000; Williams 2004; Ahmed et al.
2007).

Perceived discrimination as a stressor

The term, racism, refers to an organized system that categorizes population groups into ‘races’,
and uses this ranking to preferentially allocate societal goods and resources to groups regarded
as superior (Bonilla-Silva 1996). Fundamental to racism is cultural racism that undergirds an

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ideology of inferiority that ranks some racial groups as inherently or culturally superior to
others and supports the social norms and institutions that implement this ideology (Jones
1997). Racism often leads to the development of negative attitudes and beliefs toward racial
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outgroups (prejudice), and differential treatment of members of these groups by both

individuals and social institutions (discrimination). Importantly, because racism is deeply
embedded in the culture and institutions of society, discrimination can persist in institutional
structures and policies even in the context of marked declines in individual level racial prejudice
and discrimination. Moreover, negative racial stereotypes that are deeply rooted in mainstream
culture can serve as an additional source of discriminatory behavior even among persons who
may not be prejudiced. Considerable scientific evidence indicates that discrimination persists
in multiple contexts of American society including housing, labor markets, criminal justice
and education (Blank et al. 2004; Fix and Struyk 1993). Targets of discrimination are aware
of some of the discriminatory behavior directed at them and these perceptions of unfair
treatment can generate stress (Clark et al. 1999).

Perceived racial or ethnic discrimination is one aspect of racism that is increasingly receiving
empirical attention as a class of stressors that could have consequences for health and for
understanding disparities in health. This is consistent with broader interest in the role of stress
as a determinant of social disparities in health (Pearlin et al. 2005). Stress appears to accelerate
cellular aging (Epel et al. 2006) and the chronic stressors triggered by multiple environmental
assaults can lead to wear and tear on the body that can dysregulate multiple biological systems
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and lead to premature illness and mortality (Seeman et al. 2004). A word about terminology
—in this paper, we use the terms discrimination, perceived discrimination, interpersonal
discrimination and self reported discrimination interchangeably. We also use the term racial
discrimination to refer to both racial and ethnic discrimination.

Prior reviews of the early research on discrimination and health have found an inverse
association between discrimination and morbidity (Williams et al. 2003; Krieger 1999). Mental
health status was the most frequently used health outcome and other self-reported indicators
of health were widely used. Most early studies were U.S.-based and cross-sectional in design.
To assess the current state of the empirical evidence on discrimination and health, we conducted
a systematic review of the PubMed database to update the recent review by Paradies (2006)
which covered the period of 2000–2004. We used the search terms racism, racial
discrimination, race and discrimination, perceived discrimination, prejudice, racial prejudice,
racialized prejudice, race discrimination, racialized discrimination, ethnic discrimination,
social discrimination, racialized and racialization to identify relevant studies published
between 2005 and 2007. Our search initially yielded 5,107 articles. These articles or their
abstracts were individually reviewed to select only those published during the three year period
2005–2007 (epubs for 2008 publications were excluded), that empirically examined the
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association between a measure of perceived discrimination and an indicator of health status or

healthcare utilization. One hundred and fifteen papers met our criteria (Table 1). We
acknowledge that focusing only on PubMed does not provide a comprehensive picture of all
of the published research on this topic since the work of some social scientists is not included
in this database. It nonetheless serves to illustrate the growing scientific interest in this subject.

Trends in the recent literature

Studies of mental health continue to dominate the discrimination and health literature. Forty-
seven studies are listed under the mental health category in Table 1 but several other articles
that included a mental health measure are listed under the other summary categories because
multiple indicators of health were utilized. A broad range of mental health outcomes has been
examined in recent papers. These include studies that have examined the relationship between
discrimination and schizophrenia among ethnic minorities in the Netherlands (Veling et al.

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2007), burn-out in U.S. medical students (Dyrbye et al. 2007), daily moods among multi-ethnic
U.S. adults (Broudy et al. 2007), cognitive impairment among black and white university
students (Salvatore and Shelton 2007), and current rates of psychiatric disorders in a national
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sample of Asian Americans (Gee et al. 2007b). Discrimination has also been associated with
homesickness among college students (Poyrazli and Lopez 2007) and conduct problems among
adolescents (Brody et al. 2006). Other recent research has related perceived discrimination to
multiple forms of violence (Choi et al. 2006). These include intimate partner violence
(Waltermaurer et al. 2006) and violence among adolescents (Simons et al. 2006). Almost
without exception, studies of discrimination and mental health find that higher levels of
discrimination are associated with poorer mental health status. At the same time, almost all
studies are cross-sectional leaving open the possibility that perceptions of discrimination are
a consequence of mental health status. It is therefore noteworthy that the few published
prospective studies (Brody et al. 2006;Greene et al. 2006;Simons et al. 2006;Schulz et al.
2006b), have found that there is a positive association between perceived discrimination and
changes in mental health symptoms. This pattern is consistent with one earlier national study
of African Americans which found that baseline depression and depressive symptoms were
not associated with subsequent reports of discrimination (Brown et al. 2000).

There has long been interest in the relationship between discrimination and blood pressure
(Williams and Neighbors 2001; Brondolo et al. 2003), as well as, cardiovascular disease more
broadly (Wyatt et al. 2003). Table 1 lists eight recent studies that use laboratory experiments
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to expose individuals to analogues of racist events. The studies of cardiovascular reactivity

find that acute experiences of stress continue to be related to increases in blood pressure
reactivity in the laboratory setting. However, our understanding of the relationship between
exposure to discrimination and the sustained elevation of blood pressure remains elusive. In
recent studies, the patterns remain complex and unclear. While one study found a U-shaped
association between discrimination and systolic blood pressure among Latinos and African
Americans in New Hampshire (Ryan et al. 2006), some other studies have not found an
association between perceived discrimination and blood pressure. This includes analyses of
3,300 middle-aged women in the MESA study (Brown et al. 2006). In a study of black and
white adolescents, unfair treatment attributed to race was unrelated to ambulatory blood
pressure, but unfair treatment due to physical appearance was (Matthews et al. 2005). Table 1
uses the term “conditional association” to indicate the absence of an association between
discrimination and health in the overall sample, but with the existence of an association only
for some sub-group. This pattern dominates the recent studies of discrimination and blood
pressure. In analyses of 2,316 cases of incident hypertension in the Black Women’s Health
Study (BWHS, Cozier et al. 2006), although discrimination was unrelated to incident
hypertension in the total sample, it was positively related among women born outside of the
U.S. In the Metro Atlanta Heart Disease Study, although discrimination was unrelated to blood
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pressure, high levels of stress due to discrimination were predictive of increased hypertension
risk (Davis et al. 2005). Moreover, some of the conditional findings are counterintuitive. For
example, in studies of black adolescents, discrimination was inversely related to blood pressure
only among those who responded to discrimination with a passive coping style (Clark and
Gochett 2006) or among those who were low on trait anger (Clark 2006a).

A broad range of physical health outcomes have been considered in the 21 recent studies listed
in Table 1. Several large cross-sectional studies have found a positive association between
discrimination and chronic health conditions or other self-reported indicators of ill-health.
These include a national study of Asian Americans (Gee et al. 2007a), a study of Filipino
Americans in San Francisco and Hawaii (Gee et al. 2006a), an African American sample in
the CARDIA study (Borrell et al. 2006), and a national study in New Zealand (Harris et al.
2006b). In the New Zealand study a dose–response relationship was observed between
perceived discrimination and each of the five indicators of health: self-rated health, physical

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Williams and Mohammed Page 5

functioning, mental health, cigarette smoking, and self-reported cardiovascular disease (Harris
et al. 2006b) Other cross-sectional studies have found self-reported discrimination related to
abdominal fat (Vines et al. 2007), hemoglobin A1c (Piette et al. 2006), poorer sexual
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functioning (Zamboni and Crawford 2007), nutritional risk among Black men (Locher et al.
2005) less stage 4 sleep (i.e., “deep,” or slow-wave sleep) and physical fatigue (Thomas et al.
2006). Longitudinal analyses of the large cohort of the BWHS have found a positive association
between discrimination and the incidence of uterine myomas (fibroids) (Wise et al. 2007) and
the incidence of breast cancer (Taylor et al. 2007). Other prospective analyses indicate that
perceived discrimination predicts coronary artery calcification (Lewis et al. 2006) and changes
in self-rated health (Schulz et al. 2006a).

Table 1 list 19 studies that have examined the extent to which reported experiences of
discrimination can shape health care seeking and adherence behaviors. Some studies have
focused on perceived discrimination in general while others have attended to perceptions of
bias within the health care context. While perceptions of racism were unrelated to delayed
seeking of treatment in a small study of African Americans with an acute myocardial infarction
(Banks and Dracup 2006), it has been associated with delays or failure to seek treatment for
less severe conditions in the U.S. (Facione and Facione 2007;Van Houtven et al. 2005;Wagner
and Abbott 2007;Casagrande et al. 2007) and Sweden (Wamala et al. 2007a). However, the
findings have not been uniform with discrimination unrelated to cancer screening (Dailey et
al. 2007;Hoyo et al. 2005) and the use of preventive care (Fowler-Brown et al. 2006) in some
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studies. Perceived discrimination has also been associated with the failure to seek preventative
services such as cholesterol testing, hemoglobin A1c testing and eye exams for diabetes and
flu shots (Trivedi and Ayanian 2006) and the use of alternative care instead of conventional
care (Bazargan et al. 2005). Several studies have also found an inverse association between
discrimination and satisfaction with care among African Americans and Whites (Benkert et al.
2006;Fowler-Brown et al. 2006) and Korean Americans (Jang et al. 2005).

Earlier research had also indicated an association between discrimination and cigarette
smoking and alcohol use. Recent studies reveal that perceived discrimination is associated with
an increased risk of multiple substances, such as marijuana, inhalants and cocaine among
middle school students (Choi et al. 2006). In the CARDIA study of young adults, discrimination
was associated with marijuana, tobacco and alcohol use, but not cocaine use, among black but
not white participants (Borrell et al. 2006). Similarly, both chronic and acute racial
discrimination were associated with prescription drug use, illicit drug use and alcohol
dependence among Filipino adults in San Francisco and Honolulu (Gee et al. 2007a). Other
U.S. studies continue to find positive associations between discrimination and tobacco
(Landrine et al. 2006; Krieger et al. 2005; Bennett et al. 2005) and alcohol use (Terrell et al.
2006). Studies from South Africa also find that perceived discrimination is positively
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associated with cigarette smoking (Brook et al. 2006b) and HIV risk behavior (Kalichman et
al. 2006).

Another striking pattern in the current research is the broader range of contexts that have been
considered. The earliest studies of discrimination and health disproportionately focused on the
African American population. Recent studies have included all of the other racial/ethnic
populations in the U.S. with several studies focusing on Asian American populations (Gee et
al. 2006a, 2007a, b, c; Lam 2007; Jang et al. 2005). In recent years, studies have also utilized
national samples in New Zealand (Harris et al. 2006a, b) and Sweden (Wamala et al. 2007a).
Studies from Australia continue to examine the association between discrimination and
Aboriginal health (Larson et al. 2007) and studies from the U.K. have examined discrimination
and health among African-Caribbean, Bangladeshi, and White adults (Wadsworth et al.
2007), British Muslims (Sheridan 2006), minority ethnic teachers (Miller and Travers 2005);
and multiple ethnic immigrant adults (Bhui et al. 2005; Karlsen et al. 2005). Two studies from

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South Africa have also examined discrimination in relation to adolescent risk behaviors (Brook
et al. 2006b; Kalichman et al. 2006). Studies in Norway (Oppedal et al. 2005), Denmark
(Montgomery and Foldspang 2007), the Netherlands (Veling et al. 2007; Stevens et al.
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2005a), Spain (Pantzer et al. 2006), Bosnia, Croatia and Austria (Sujoldzic et al. 2006), Hong
Kong (Lam et al. 2005) and Canada (Beiser and Hou 2006; Noh et al. 2007; Etowa et al.
2007) have examined the association between perceived discrimination and health for multiple
immigrant groups.

It is also noteworthy that very few studies explicitly examine the role of discrimination in
accounting for racial disparities in health. Some early studies provided evidence that
discrimination makes an incremental contribution to SES in explaining disparities (Williams
et al. 2003). A few recent studies find that perceived discrimination accounts for some of the
racial disparities in health. This is evident for Maori-European disparities on four indicators
of self-reported health in a national study of New Zealand (Harris et al. 2006a), Aboriginal–
non Aboriginal variations in self-reported physical and mental health in Australia (Larson et
al. 2007), and in U.S. studies for black-white differences in health care trust (Adegbembo et
al. 2006), sleep quality and physical fatigue (Thomas et al. 2006) and Hispanic-white
differences in PTSD symptoms (Pole et al. 2005).

There has also been concern regarding the extent to which subjective reports of discrimination
are independent of other psychological characteristics. Three recent studies found that the
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association between discrimination and health remained robust after adjustment for social
desirability bias (Gee et al. 2007b; Krieger et al. 2005; Pole et al. 2005). In addition, in a study
of Latino and African American adults, Brondolo et al. (2005) found that the association
between discrimination and negative emotions was independent of cynical hostility and
positive and negative affect, while a study of multiethnic adults found that the relationship
between perceived discrimination and mood was independent of trait anxiety, social
desirability and cynical hostility (Broudy et al. 2007). A study of black, white and Bangladeshi
adults in the UK found an association between discrimination and psychological distress after
adjustment for negative affect (Wadsworth et al. 2007).

Research challenges
As evidence continues to mount suggesting that perceived discrimination is a risk factor for
multiple health outcomes, there is increasing scientific interest in this area of research. For
some, this has led to the routine, mechanical and a-theoretical addition of a discrimination scale
to health studies without adequate thought regarding either the assessment of discrimination
or the underlying mechanisms and processes by which discrimination would be presumed to
affect health. We believe that the time has come for careful re-assessment of our current
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approaches to the study of discrimination and health with an eye toward investing in what is
needed to improve our scientific understanding of this phenomenon and its health
consequences. Perceived discrimination is a psychosocial stressor and there is much that can
be learned from the larger literature on stress to advance the study of discrimination and health
(Williams et al. 2003). Enhancing our understanding of discrimination and health will require
more systematic attention to comprehensively and accurately measuring discrimination,
assessing how it combines with other aspects of racism and other stressors to affect health and
paying greater attention to the underlying pathways by which discrimination can affect health.

Measuring perceived discrimination comprehensively

There is no consensus on an optimal measure of perceived discrimination. A recent review
evaluated 34 different measures of perceived discrimination (Kressin et al. 2008), but the
current conceptualization and assessment of discrimination is limited. Recent studies of
perceived discrimination and health tend to capture two domains of stressors, daily hassles and

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life events. The most widely used measure in recent studies reviewed is the Everyday
Discrimination Scale (Williams et al. 1997). The scale has several attractive features, including
its brevity, good psychometric properties (Krieger et al. 2005), and its use in multiple racial/
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ethnic populations in the U.S. and its increasing use in international contexts such as South
Africa (Williams et al. 2008). The scale attempts to capture aspects of interpersonal
discrimination that are chronic or episodic but generally minor, somewhat analogous to the
assessment of daily hassles in the stress literature. A few studies use it in conjunction with
other indicators of discrimination but it is often used as the only measure of discrimination.
Another very useful approach to capturing ongoing discrimination is the dairy approach of
Brondolo and her colleagues (Brondolo et al. 2005, 2008a, b; Broudy et al. 2007). However,
there is a need for greater awareness that measures like the Everyday Discrimination Scale
capture an important, but limited aspect of the phenomenon of self-reported discrimination.

Discriminatory experiences that are acute and observable and are analogous to life events in
the stress literature are captured by many of the other commonly used measures of
discrimination in recent studies. These include the Experiences of Discrimination scale
(Krieger 1990), the Schedule of Racist Events (Landrine and Klonoff 1996), the Major
Experiences of Discrimination scale (Williams et al. 1997; Kessler et al. 1999); the Racism
and Life Experiences Scale (Harrell 1997), and the Index of Race-Related Stress (Utsey and
Ponterotto 1996). Prior research has shown that failure to assess stress comprehensively leads
to an underestimation of the effects of stress on health (Turner et al. 1995). The current
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assessment of discrimination tends to neglect the measurement of chronic stressors in major

domains of life such as work. Chronic stressors refers to experiences that provide persistent
negative exposure to threat or excessive demand (Baum et al. 1993). The stress literature
indicates that although chronic stressors are difficult to measure, they are stronger predictors
of the onset and course of the disease than acute life events (Cohen et al. 1995). It is noteworthy
that capturing chronic exposure to discrimination over time, as assessed by the Everyday
Discrimination Scale, was associated with subclinical cardiovascular disease (Lewis et al.
2006). The Perceived Racism Scale (McNeilly et al. 1996) captures some aspects of chronic
discrimination but more effort is needed to comprehensively characterize chronic and ongoing
experiences of discrimination, especially its multiple dimensions in the domain of work, a
major site of discriminatory experiences in contemporary society.

Traumas are a class of stressful experiences that can have long-lasting negative effects on health
(Stam 2007; Pearlin et al. 2005), that have been neglected in the discrimination literature.
Traumas are distinct from life events in that they capture events that are extreme, overwhelming
and horrific in impact. It is likely that traumatic experiences are reported on some of the life
events-like measures of discrimination but inadequate detail is ascertained to distinguish them
from less severe experiences. Carter (2007) has emphasized the importance of assessing race-
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based traumatic experiences as distinct from major experiences of discrimination. He argues

that because there is likely to be intense emotional reaction to these severe, life threatening or
dangerous experiences, they have great potential for psychological injury.

The stress literature has also recognized macro-stressors as one component of stressor
exposure. These are large-scale system-related stressors such as economic recessions or natural
disasters. They provide indirect exposure to stressors, that can have “collateral effects” on
individuals (Yehuda et al. 2005). Research reveals that events such as earthquakes, terrorist
attacks and the onset of war can trigger increases in acute symptoms of heart disease, increased
hospital admissions and heart disease mortality (Bhattacharyya and Steptoe 2007). Highly
publicized race-related traumatic events, such as extreme examples of police brutality could
have similar effects. Some of the items on the Index of Race-Related Stress (such as references
to racial abuses of the Jim Crow era) capture aspects of macro-stressors (Utsey and Ponterotto
1996) but comprehensively assessing the potential contribution of large-scale, race-related

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traumatic events will require researchers to capitalize on emergent opportunities to assess the
health consequences of macro-stressors. Such efforts could utilize some of the strategies used
in the larger stress literature such as creatively using hospital admissions and vital statistics
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data. Future research needs to identify the extent to which major race-related stressors can
initiate new disease processes or exacerbate existing disease. There is no agreement in the
stress literature on the length of time from the emotional trigger from a macro-stressor to the
onset of symptoms. However, some research suggests that cardiac mortality tends to be
elevated for at least 6 months post-bereavement (Bhattacharyya and Steptoe 2007).

Researchers should also be alert to the possibility that macro-stressors that are ostensibly
unrelated to race or ethnicity, can be racialized in ways that can generate increased
discrimination for socially stigmatized groups. The terrorist attacks on 11 September 2001 are
an example. These incidents had documented negative health consequences (DiMaggio et al.
2007), but they also triggered increased discrimination and harassment targeted to Arab
Americans in the 6 months after the terrorist attacks (Lauderdale 2006). Lauderdale (2006)
found that Arab American women in California had an increase in the rate of low birth weight
and pre-term birth in the 6 months after September 11 compared to the 6 months before. Other
women in California did not experience a change in birth outcome risk post September 11.

Assessing exposure to racial discrimination in its full complexity also requires attention to
capturing the effects of discrimination on others and the potential intergenerational effects of
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racism. Few measures of discrimination ask questions about experiences of discrimination that
occurred in the lives of family members and close friends of the respondent (Kressin et al.
2008). In contrast, the stress literature has long noted that vicarious experiences of stress can
also adversely affect the individual (Cohen et al. 1995). One recent study found that the father’s
experience of workplace discrimination was positively associated with his depressive
symptoms, as well as, those of his family members (Crouter et al. 2006). Recent research on
the effects of historical trauma on the health of American Indians illustrates the importance of
assessing this dimension of racism (Whitbeck et al. 2004; Brave Heart 2003; Brave Heart and
DeBruyn 1998). The term historical trauma refers to the cumulative psychological wounding
of an individual and his/her group due to the history of genocide and other atrocities that
American Indians and other indigenous people experienced from European colonizers. The
explicit attempt is to capture such exposure over the life-span of the individual and across
generations. Research highlights the importance of assessing not only the actual experiences,
but also the role that traumatic reminders of these experiences can play (Stam 2007).
Assessment instruments with good psychometric properties have been developed to assess
historical trauma and have found, for example, that some 50% of American Indians think
regularly about these historical losses (Whitbeck et al. 2004). Empirical studies have also linked
exposure to historical trauma to multiple health outcomes. This research is similar to studies
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of other generational group traumas, including studies of the health consequences of the Jewish
Holocaust on survivors and their descendants. The assessment of these traumas in future
research should be expanded to include other race-specific experiences such as the historic
brutal lynchings of blacks and the internment and re-location of Japanese Americans during
the Second World War.

Measuring discrimination accurately

Enhancing our understanding of discrimination and health will also require greater attention
to identifying strategies to address the limitations of the currently used measures. Problems
that have been identified with the reliability and validity of traditional life event scales also
apply to most measures of discrimination (Monroe 2008). These problems include unreliability
of recall, recall bias, criterion validity and construct validity have (Dohrenwend 2006). It is
important to capture exposure to discrimination over the life course and the most common time

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frame for the assessment of discrimination is lifetime exposure (Kressin et al. 2008). This is
appropriate given the goal of capturing cumulative exposure over the life course. However,
problems linked to recall are more severe when the recall period of stressors is longer and when
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the data are gathered from retrospective reports. Of particular concern are some studies of
PTSD that suggest that recall bias can lead to an overestimation of a dose–responsive
relationship between exposure and outcome (Dohrenwend 2006). Current mood affects
memory retrieval and both depressed and PTSD patients have impaired retrieval in terms of
memory (Harvey and Bryant 2002). A study of motor vehicle accident victims who provided
symptoms one month after the incident and were asked to recall those symptoms two years
later found that the severity of the stress and injury and the trajectory of recovery can lead to
over reporting or under-reporting of symptoms (Harvey and Bryant 2000). While the majority
correctly recalled most of the symptom clusters, persons with few symptoms two years later
tended to omit symptoms that they had reported in the acute phase of the disease, and persons
with high levels of symptoms at the two year interview were more likely to recall the presence
of acute symptoms that they had not reported in the initial assessment.

Research reveals that severe events are recalled better than less severe events (Monroe 2008),
so to the extent that the focus is on the assessment of severe discriminatory incidents the recall
problem may be somewhat minimized. More importantly, the assessment tools for the
assessment of discrimination need to be appropriate to the task. More research is needed on
how experiences of racial discrimination are stored in memory and best accessed for recall. In
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the meantime, research studying lifetime exposure to discrimination should consider using an
event history calendar. It is a procedure that has been developed by cognitive psychologists
that capitalizes on current scientific understanding of the nature of autobiographical memory
to assess experiences over the life course (Belli 1998). More generally, research by cognitive
psychologists and survey methodologists provide many insights into how respondents
understand, interpret, and respond to questions that would enhance the collection of data on
discrimination (Schwarz 2007). We consider a few examples.

The sensitive nature of the topic of race and racial discrimination has implications for how the
discrimination variable should be assessed and the accuracy of reports of discrimination
(Williams et al. 2003). Recent research on race-of-interviewer effects indicates that blacks are
reluctant to reveal their true racial beliefs on race sensitive questions when talking to white
interviewers. Instructively, Krysan and Couper (2003) found that the strongest effect of blacks
being deferent to a white interviewer was for perceptions of racial discrimination (compared
to attitudes on four other categories of race-related questions regarding racial and race-
associated policies, black politics and the pace of civil rights). This pattern held both for in-
person interviews and for self-administered interviews with a digital video of the interviewer.
Irrespective of the race of the interviewer, making race salient in the assessment of
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discrimination can lead to response bias compared to the use of neutral terminology (Gomez
and Trierweiler 2001). Many questions used to assess discrimination explicitly ask respondents
to report on “racial discrimination” or experiences of discrimination “because of your race.”
In contrast, the approach of Williams and his colleagues (Williams et al. 1997; Kessler et al.
1999) frames the questions about discrimination in terms of unfair treatment and asks about
attribution only after a behaviorally descriptive experience, without emotionally charged
language, has been endorsed. This approach seeks to address not only the problem of the
sensitivity of questions regarding discrimination but also concerns about the problem of
attributional ambiguity. Respondents are often uncertain of the reason (or attribution) for a
specific interpersonal incident. Thus, building attribution into the question is likely to
underestimate discriminatory encounters for which the attribution is uncertain (Williams et al.
2003). Asking questions about both racial and non-racial discrimination may capture more of
the potential pathogenic phenomenon of perceived unfairness, and also reduce some of the
measurement error that can occur if questions are asked only of racial discrimination. However,

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there is debate regarding optimal measurement approaches for perceived racial discrimination
(Kressin et al. 2008), and limited empirical evidence on the effects, if any, that building
discrimination and racial terminology into the assessment of perceived discrimination has on
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respondents’ willingness and ability to recall and report these experiences.

An unresolved issue in the literature is the extent to which unfair treatment based on race may
have effects that are distinctive from other forms of unfair treatment. Because of the centrality
of race in American society, the salience of racial identity can affect the appraisal processes
of some individuals in ways that could lead race-attributed experiences to be more impactful
because they are especially threatening to an individual’s sense of rights and opportunities
(Pearlin et al. 2005). Some studies have found that perceptions of racial and non-racial
discrimination are similarly related to health (Williams et al. 1999; Kessler et al. 1999). Recent
neuroimaging research indicates that the experience of unfairness is associated with negative
emotional responses and can activate regions of the brain involved with emotional regulation,
suggesting that seeking justice and fairness may be a basic human impulse and its violation
can trigger physiological consequences (Tabibnia et al. 2008). Accordingly, irrespective of
attribution, the perception of unfair treatment may generate distress. For example, in the
Whitehall study, perceived unfairness has been related to incident coronary events (De Vogli
et al. 2007a), incident psychiatric morbidity (Ferrie et al. 2006), and metabolic syndrome (De
Vogli et al. 2007b). These studies were not framed within the context of discrimination but
unfairness is operationalized with measures similar to those used in the discrimination
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literature.

Lewis et al. (2006) recently reported that although Everyday Discrimination attributed to race
was unrelated to coronary calcification for black women, a combined measure capturing racial
and non-racial discrimination was positively associated with coronary calcification. On the
other hand, one study found that black women who attributed chronic discrimination to race
demonstrated greater blood pressure reactivity than those who attributed them to other social
status categories (Guyll et al. 2001). Future research needs to more systematically assess the
extent to which racial discrimination differs in its causes and consequences from other types
of discrimination and the extent to which the approach to capturing attribution affects our
understanding of the levels and health consequences of racial discrimination. Some limited
evidence suggests that racial discrimination as a stressor may differ from other stressors,
possibly because its threat may be more systematic, insidious and constant than other stressors
(Stetler et al. 2006).

More generally, research on asking sensitive questions in survey research reveals that to the
extent that respondents perceive questions regarding discrimination to be socially unacceptable
or undesirable, they are likely to underreport those experiences (Tourangeau and Yan 2007).
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Research reveals that the mode of administration of sensitive questions makes a difference in
terms of the response. In particular, the presence of others in the interview context adversely
affects accurately collecting complete data. Thus, eliminating the presence of an interviewer
by using a self-administered instrument and using “forgiving” or normalizing wording for
sensitive questions can be helpful in addressing this issue (Tourangeau and Yan 2007).

Measuring discrimination accurately will also require researchers to not only capture the
multiple domains of discrimination but to ensure that adequate questions are asked in each
domain. In the assessment of multiple phenomena, survey methodologists find that multiple
questions about components of a phenomenon will provide a more accurate level than a few
global questions (Schaeffer and Presser 2003). Multiple questions are more likely to clearly
convey what is being asked and to yield a more thorough search of memory. For example,
researchers have found that population-based reports of alcohol consumption markedly under-
report alcohol use compared to data on taxable alcohol available for consumption. However,

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assessing alcohol use with detailed, within-location, beverage-specific questions (asking

respondents whether they had consumed specific alcoholic beverages, at any of several specific
locations and then about how much and how often they drank in each location) accounted for
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94% of the taxable alcohol available for consumption compared to the 40–60% with standard
alcohol use questions (Casswell et al. 2002). For each class of discriminatory experiences,
similar attention should be given to ensuring that all relevant contexts and components are
assessed.

A challenge to getting a valid measure of discrimination via self-report is that some individuals
cope with stress by denying its occurrence. Studies reveal that among patients with cancer,
four to 47% deny the diagnosis, 8–70% deny the impact and 18–42% deny affect (Vos and de
Haes 2007). Related constructs include avoidance, distancing, suppression and repressive
coping. Denial can reflect conscious or unconscious efforts to minimize the pain of negative
experiences. It has been argued that the emotional pain of racism can render some individuals
unable to recall specific events (Carter 2007). Vos and de Haes (2007) suggest that denial
should be viewed not as a one-time event, but as a process in which there is a continuum from
facts to ambiguous events. Accordingly, denial can be a passive escape strategy linked to poorer
psychological function, or it can be part of a series of active distractive strategies that are
adaptive and lead to lower levels of psychological distress. Getting a clearer sense of the levels
and consequences of denial in research on discrimination should be a priority for future
research.
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One of the most impressive patterns in the recent literature on racial discrimination is the broad
range of national contexts in which it has been studied. Undoubtedly, there are some
commonalities to the manifestation of discrimination. However, as with other stressors, culture,
history and social context can determine the kinds and categories of stressful experiences. As
studies of discrimination continue to proliferate across racial, ethnic, cultural, national, and
socioeconomic contexts, researchers should ensure that the assessments of discriminatory
experiences are appropriate to the specific population group under study. National data for
South Africa reveals that levels of chronic Everyday Discrimination and major acute
experiences of discrimination are markedly lower than in the U.S. (Williams et al. 2008). It is
currently unclear whether this variation reflects national or cultural differences in the levels of
discrimination, the discourse about race, the willingness to report experiences of
discrimination, the level of social interaction between dominant and non-dominant racial
groups, or the applicability of measures of discrimination developed in the U.S. to a different
context. Measuring discrimination comprehensively will require more explicit attention to
assessing the relevant forms of its manifestation in specific contexts.

Assessing the stressful dimensions of discrimination

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An important lesson from the stress literature for researchers studying discrimination is that
exposure to most stressful experiences does not lead to illness. The overwhelming majority of
persons exposed to even the most severe traumatic life experiences have transient symptoms
in response to these problems (Yehuda et al. 2005; Baum et al. 1993; Cohen et al. 2007). While
there are emotional reactions and symptoms in response to severe stressors, most of them are
resolved in the ensuing weeks or months. For example, after a trauma most people recover
from symptoms in a year and only 5–10% of those exposed to traumatic experiences go on to
develop PTSD (Bryant 2003; Carter 2007). However, the relationship between stress and health
status may vary by health outcome with an estimated 20–25% of people who experience major
stressful life events developing major depression (Cohen et al. 2007).

The challenge then is to identify and assess those dimensions of discriminatory experiences
that are likely to have long-term negative effects. The stress literature suggests that several

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characteristics of stressors are important determinants of the long-term negative impact of

stress. Stressors that are ambiguous, negative, unpredictable, and uncontrollable are
particularly pathogenic (Carter 2007; Dougall et al. 1999). The intensity of the stressor also
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matters including how disturbing and upsetting it is (Dougall et al. 1999). The frequency and
duration of stressors are also key determinants of their impact with chronic or repeated stressors
or prolonged exposure being predictive of adverse effects. Such stressors or difficulties are
likely to make continuing demands or pose ongoing threats (Dohrenwend 2006). The impact
that the stressor has on the environment and social functioning of the individual is also
important. Stressors that occur in central role areas of an individual’s life, affect multiple areas,
lead to loss of resources, have objective negative impact on the normal activities of the
individual, and cause a lot of change, disruption or readjustment are likely to be very
consequential (Dohrenwend 2006; Carter 2007). The presence of symptoms such as post
traumatic or peritraumatic disassociation and of panic reactions appear to predict long term
negative effects of exposure to traumas (Yehuda et al. 2005).

An important priority in the future assessment of perceived discrimination is to assess markers

of the stressfulness of experiences. A central problem in the assessment of stress is what
Dohrenwend (2006) calls “intracategory variability.” That is, the categories on life events
scales are typically so broad (death of a loved, unemployment, or serious illness or injury) that
they capture experiences that can vary in their stressfulness and impact. Knowing that such an
event occurs provides no information on how negative, unexpected, and undesirable, the event
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was. The same is true for measures of discrimination in employment, housing or in interaction
with the police. Researchers studying discrimination should devote more attention to assessing
the severity of discriminatory incidents by capturing the number, intensity, and duration of
these experiences (Carter 2007).

The stress literature offers three options for assessing severity. First, the narrative-rating
methodology is a labor intensive interview that gathers details about each potentially stressful
experience so that trained researchers can then rate them on multiple dimensions of
stressfulness (Dohrenwend 2006). This approach has been shown to be superior to standard
checklists of stressful events but because interviewing and rating can take as much as 16 hours
per individual interview (Dohrenwend 2006), it is too time consuming and expensive to be a
practical option for most researchers. A second approach is to clearly define what kinds of
experiences should be included in a category and/or spell out the inclusion or exclusion criteria
for the target stressful experience (Dohrenwend 2006). For example, in the Traumatic Life
Events Questionnaire (Kubany et al. 2000), instead of asking the respondent if s/he had been
in a motor vehicle accident, the respondent is asked “were you involved in a motor vehicle
accident for which you received medical attention or that badly injured or killed someone.”
Similarly, the question assessing the presence of childhood physical abuse is “were you
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physically punished in a way that resulted in bruises, burns, cuts or broken bones?” (Kubany
et al. 2000). This strategy could be applied to questions about racial discrimination in which
behaviorally descriptive language that avoided global and emotionally charged words could
clearly specify the experiences that should be included. This approach can improve assessment
but has the downside of potentially missing other important stressors that do not fall within the
specified criteria (Dohrenwend 2006).

A third strategy involves subjective ratings by the respondent of the severity and negative
impact of the stressful experience (Cohen et al. 2007). In the PTSD literature, respondents are
often asked after reporting a particular event to indicate how much they had been affected by
it and how upset they had been by it (Carter 2007). Similarly, a study relating caregiver stress
to mortality had respondents indicate “how much of a mental or emotional strain” each reported
caregiving task had been (Schulz and Beach 1999). A recent measure of hurricane-related
stressors required respondents to provide a global rating of the 29 stressors ascertained by

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indicating “how stressful overall” the experiences had been on a 0–10 scale, “where 0 means
not at all stressful and 10 means the most stressful thing you can imagine” (Kessler et al.
2008). The researchers then compared respondents rating their stress as severe (9–10), serious
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(7–8), moderate (5–6) or mild (3–4) to those who did not rate it as stressful (0–2). Such
approaches lead to stronger associations between life events and mental health in the general
stress literature (Dohrenwend 2006), but this approach has been used in only a few studies in
research on discrimination and health.

Analysis of data from the Metro Atlanta Heart Disease Study illustrates the promise of this
approach. This study found that although perceived discrimination was unrelated to
hypertension, both discrimination at work (Din-Dzietharn et al. 2004) and discrimination more
generally (Davis et al. 2005) were associated with increased risk of hypertension, but only
among persons reporting high levels of stress because of discrimination. In this study, if
respondents reported experiences of discrimination they were asked to rank their general level
of stress when they had those experiences from 1 = none to 5 = high. Several states participating
in the annual Behavioral Risk Factor Surveys in the U.S. have included the Reactions to Race
module, developed by Camara Jones, which includes questions that assess emotional and
physical symptoms as a result of exposure to discriminatory experiences. This is a fertile
opportunity to explore the contribution of ratings of severity to the association between
discrimination and health. One limitation of obtaining appraisals of stressfulness is that for
studies of mental health, respondents’ reports of stressfulness can lead to confounding between
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the measure of stress and the self-reported outcome (Dohrenwend 2006).

Other evidence suggests that two aspects of a discriminatory experience that can affect its
stressfulness are the degree of ambiguity of the situation and the identity of the perpetrator.
Limited evidence from the discrimination literature indicates that characteristics of the
perpetrator can predict the degree of adverse impact with the effects being more negative when
the perpetrator belongs to the same racial group as the target (Mays et al. 2007). The ambiguity
surrounding an experience of discrimination can also be a determinant of its stressfulness, and
greater attention should be given to assessing attributional ambiguity (Carter 2007). Several
recent studies have noted stronger, more negative effects from subtle or ambiguous racial
encounters than from blatant ones (Bennett et al. 2005; Stetler et al. 2006; Merritt et al.
2006). There may also be racial differences in the effects of ambiguity. A recent study of
university students found that blacks experienced greater impairment in cognitive functioning
when faced with ambiguous evidence of prejudice than when exposed to blatant prejudice
(Salvatore and Shelton 2007). The opposite pattern was evident for whites. It may be that the
socialization of blacks may enable them to cope better with blatant than subtle prejudice while
the socialization of whites may lead them to fail to perceive subtle prejudice. Routinely
assessing the extent to which racial attribution is uncertain appears to be an important priority
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in the future measurement of discrimination.

Measuring vigilance and anticipatory stress

Vigilance regarding the threat of discrimination and the anticipation of future occurrences of
discrimination could be as predictive of the adverse health impact as the actual effects of past
discriminatory experiences. The negative physiological effects of exposure to stressors are
often triggered by the initial perception of threat which can occur long before the actual
exposure to the stressor. Several researchers have emphasized that anticipatory coping and
anxiety, heightened vigilance, and intrusive thoughts or images can play an important role in
determining the negative effects of stressors on health (Yehuda et al. 2005; Pearlin et al.
2005; Carter 2007; Baum et al. 1993; Dougall et al. 1999). This may be especially important
for the stress linked to racial discrimination because one’s racial status is a characteristic that

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a respondent can do little about. Carter (2007) uses the term “cultural paranoia” to refer to a
high level of vigilance that many minority group members maintain.
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Brosschot and colleagues (2006) use the term “perseverative cognition” to capture worry,
rumination and anticipatory stress. They review evidence from multiple sources that suggests
that repeated or chronic activation of the cognitive imagery of one or more psychosocial
stressors can serve to prolong the stress and exacerbate the negative effects of stress on health.
These chronic cognitive processes can lead to “prolonged physiological activation.” The
resulting anticipatory stress, reflected in chronic or sustained vigilance can lead to
dysregulation of both emotional and physiological functioning. Considerable evidence
suggests that prolonged physiological activation is a risk factor for multiple disease conditions
(Brosschot et al. 2006). Thus, capturing the level of anticipatory stress, worry, rumination,
regarding the threat of discrimination is an important priority for future research. Williams
(1997) has suggested that the finding of elevated nocturnal blood pressure levels of African
Americans during sleep could reflect a heightened vigilance and a failure to ever completely
relax because of the constant threat of discrimination and other dangers linked to residence in
hostile residential contexts. Recent research has shown that discrimination contributes to
African Americans’ failure to display the expected nocturnal decline in blood pressure
(Brondolo et al. 2008a). Despite its importance, issues of vigilance have seldom been addressed
in the research on discrimination. Lindström (2008) recently reported that a single-item
indicator of anticipatory ethnic discrimination was associated with lower levels of
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psychological health in a national sample of adults in Sweden. In a study of African American

youth, Clark et al. (2006) found that a measure of racism-related vigilance was inversely related
to large arterial elasticity (a preclinical index of cardiovascular function) for boys but not girls.
The mean age of this sample was 12 years old suggesting that the processes may begin early
in life and future research should attend to the potential gendered nature of these responses.

Perceived discrimination and the multiple mechanisms of racism

Perceived discrimination is a historically neglected race-related aspect of life that may
adversely affect health. However, it does not comprehensively capture the effects of racism in
society. Some researchers erroneously assume that a scale that assesses racial discrimination
captures a respondent’s exposure to racism. Perceived discrimination, though important, is
only one component of racism. We briefly consider some of the other pathways by which
racism can affect health. Fully capturing the role of racism in health will require an
understanding of how discrimination combines with other aspects of racism to increase the risk
of disease.

Residential segregation
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Arguably, the most decisive way in which racism can affect health is through institutional
mechanisms of racism. The aspect of institutional discrimination most widely studied for its
health implications has been residential segregation (Williams and Collins 2001; Acevedo-
Garcia et al. 2003). This body of research indicates that residential segregation can shape SES
and thus health by restricting access to education and employment opportunities, discounting
the economic value of a given level of SES, and creating health-damaging conditions in
residential environments. Historically, two pronounced patterns of residential segregation in
the U.S. have been the geographic isolation of American Indians on reservations and the
residential concentration of African Americans in poor urban areas. There is growing concern
about the health consequences of the persisting segregation of blacks and American Indians
and the increasing segregation of Latinos (Acevedo-Garcia et al. 2008). Although the majority
of poor persons in the U.S. are white, poor white families are not concentrated in the ways that
poor blacks and Latinos are. The critical determinant of the problems linked to segregation is

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not racial composition per se but the concentration of economic and social disadvantage and
the absence of an infrastructure that promotes opportunity.
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Research has linked residential segregation to an elevated risk of illness and death (Williams
and Collins 2001; Acevedo-Garcia et al. 2003). There are multiple pathways through which
the concentrated poverty created by segregation can adversely affect health (Williams and
Collins 2001; Schulz et al. 2002). First, the conditions created by poverty and segregation make
it more difficult for residents to adhere to good health practices. The higher cost, poorer quality,
and lower availability of healthy foods in economically disadvantaged neighborhoods can lead
to poor nutrition. The heavy targeting of disadvantaged minority communities with advertising
for tobacco and alcohol can encourage the use of these products. The lack of recreation facilities
and concerns about personal safety can discourage leisure time physical exercise. Second, the
concentration of poverty can lead to exposure to elevated levels of economic hardship and
other chronic and acute stressors at the individual, household and neighborhood level. Third,
the weakened community and neighborhood infrastructure in segregated areas can also
adversely affect interpersonal relationships and trust among neighbors. Fourth, the institutional
neglect and disinvestment in poor, segregated communities contributes to increased exposure
to environmental toxins, poor quality housing and criminal victimization. Thus, perceived
discrimination must be understood and assessed within the larger context of institutional racism
which has created differential exposure to a broad range of stressors.
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Differential access to societal goods and resources

Institutional and individual discrimination can also reduce non-dominant groups’ access to a
broad range of desirable goods and services. Medical care is one example. Discrimination can
affect both access to care and the quality and intensity of medical treatment. U.S. research
reveals that residential segregation can affect access to medical care by determining both the
particular institutions where minorities access care and the type and quality of their health care
providers. In segregated minority communities, health care facilities are more likely to close,
pharmacies are less likely to be adequately stocked with medication, and residents are more
likely to be treated by lower-quality physicians who are less able to refer to specialty care
(Williams and Jackson 2005). In addition, there are large racial/ethnic differences in the quality
and intensity of medical care with blacks and other minorities receiving fewer medical
procedures and poorer quality medical care than whites (Smedley et al. 2003). This pattern
persists even when differences in health insurance, SES, stage and severity of disease, co-
morbidity, and the type of medical facility are taken into account. Cultural racism has led to
pervasive negative racial stereotypes of racial groups regarded as inferior (Williams 2004).
Some evidence suggests that unconscious discrimination based on these negative stereotypes
of minorities is a likely determinant of this pervasive bias in the delivery of care (van Ryn
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2002; Green et al. 2007).

Discrimination and other stressors

As noted, the experience of self-reported discrimination is not a magic bullet that captures all
of the psychosocial stressors necessary to estimate the contribution of racism-generated
stressors to disparities in health. Perceived discrimination is only one way by which racism
generates stress. Institutional discrimination can generate multiple stressors that can adversely
affect health. For example, institutional discrimination in employment and residential contexts
can trigger elevated exposure to traditional stressors, especially those linked to social and
economic deprivation, including unemployment and underemployment. A large federal survey
found that even after adjustment for a broad range of demographic, SES, and health status
factors blacks were more likely than whites to report six economic hardships (unable to meet
essential expenses, pay full rent or mortgage, pay full utility bill, or had utilities or telephone

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Williams and Mohammed Page 16

shut off or was evicted from one’s apartment; Bauman 1998). Similarly, because of the
distinctive residential environments created by segregation, racial minorities are also exposed
to elevated levels of neighborhood stressors and violence. Taking institutional discrimination
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seriously will require renewed focus on racial differences in traditional stressors: violence,
criminal victimization, neighborhood conditions, financial stress, and relationship stress.
Relatedly, all racism-related stressors must be situated within the context of the total stress
burden of respondents’ lives with the recognition that racism (interpersonal and institutional)
is only one source of stress. As a practical matter, researchers typically lack adequate
information to determine the extent to which other stressors are race-related or not but must
seek to characterize all stressors. Thus, understanding the potential contribution of stressful
life experiences to racial disparities in health necessitates the assessment of perceived
discrimination and a systematic effort to assess race-related and other social, psychological
and environmental (physical and chemical) stressors that respondents face.

Pearlin et al. (2005) emphasized that the stressors that are patterned by social disadvantage are
the “serious stressors” that capture major hardships, conflicts, and disruptions in life. These
include disorderly transitional events which are role changes that are non-normative, undesired,
involuntary and sometimes irreversible, such as teenage parenthood or school dropout. These
stressors are concentrated among low SES groups and in addition to their negative emotional
impact, they are critical in transmitting social disadvantage from one generation to the next
because they tend to place low SES persons on trajectories of low education, low job prospects,
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and low income that lead to the proliferation of other stressors. Financial stressors, especially
those that are characterized by continuity and repetitiveness over the life course are among the
most powerful of stressful life experiences (Pearlin et al. 2005). Other sources of social and
economic adversity, especially those that are chronic and recurring and that occur in major
social domains such as the role of breadwinning, work, and family should also be assessed.

Discrimination should be assessed within this larger social context of the multiple stressful
exposures within which it is embedded. Research is needed to elucidate, in careful longitudinal
analyses, how perceived discrimination relates to other types of stressors and combines with
them to produce patterns of cumulative exposure to multiple adversities that can adversely
affect health status. The processes may be complex. Experiences of discrimination such as the
loss of one’s job can easily lead to “stress proliferation processes” in which the primary stressor
of unemployment can give rise to multiple other types of secondary stressors, such as financial
strain and family conflict (Pearlin et al. 2005). Traumas are among the most potent types of
stressful experiences that can trigger stress proliferation with the secondary stressors that are
triggered by traumas contributing more to later health than the primary trauma itself (Pearlin
et al. 2005).
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Understanding how discrimination relates to other stressors will require examining the ways
in which multiple forms of psychosocial stress accumulate to adversely affect health. The stress
literature suggests that one’s ability to manage a new stressor is reduced by the burden and
demands of preexisting stressors (Cohen et al. 2007). Moreover, stressors may combine not
only in additive ways but also in interactive ways. Future research on perceived discrimination
should pay special attention to potential interactions among stressors. This includes attention
to environmental stressors linked to the physical, chemical, and built environment. Some
limited evidence indicates that psychosocial stressors and environmental factors may interact
with each other. One study found that high levels of air pollution were associated with distress
among people with recent life events, but unrelated to distress among persons with no social
stressors (Evans et al. 1987). Another study of an Indian sample, and two U.S. college student
samples, found that social stressors adversely affected mental health only among persons living
under the environmental condition of crowding (Lepore et al. 1991).

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Williams and Mohammed Page 17

Future research needs to sensitively and thoroughly categorize the stressors in the social
environments within which vulnerable populations live and work. These residential and
occupational environments can be distinctive in the types and quantity of stressors to which
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individuals are exposed. Efforts are needed to catalogue and quantify exposures linked to the
physical, chemical and built environment and assess how they combine with psychosocial
stressors (including discrimination) and accumulate over the life course. Special attention
should be given to the potential of differential effects of chemical exposures. Prior research
indicates for example, that smoking has more negative effects on some vulnerable minority
populations than on whites. Research also needs to explore biological profile differences across
groups with the recognition that not all biological profile differences are driven by underlying
genetics, but some could reflect complex interactions between exposure to disadvantaged
environments and biology.

Internalized racism
Internalized racism or self-stereotyping is another mechanism by which the larger negative
stereotypes about race can adversely affect health. One response of stigmatized racial
populations to the categorical societal beliefs about their biological and/or cultural inferiority
is to accept as true the dominant society’s ideology about them (Pettigrew 1964). The
internalization of negative cultural images by stigmatized groups appears to create
expectations, anxieties and reactions that can adversely affect social and psychological
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functioning. Fischer et al. (1996) show that across multiple national contexts, such as Japan,
India, the United Kingdom and Israel, groups that are socially regarded as inferior have poorer
academic performance than their more highly regarded peers. U.S. research indicates that when
a stigma of inferiority is activated under experimental conditions, performance on an
examination was adversely affected (Steele 1997). African Americans who were told in
advance that blacks perform more poorly on exams than whites, women who were told that
they perform more poorly than men, and white men who were told that they usually do worse
than Asians, all had lower scores on an examination than control groups who were not
confronted with a stigma of inferiority (Steele 1997; Fischer et al. 1996).

A study of the elderly highlights the potential health consequences of positive and negative
self-stereotyping for stigmatized groups (Levy et al. 2002). It found that positive self-
perceptions of aging, assessed at baseline, were associated with a 7.5 year longer life
expectancy in a 23 year follow-up. However, our current understanding is limited regarding
the ways in which the acceptance of negative racial stereotypes can adversely affect health.
Some evidence indicates that in addition to adversely affecting academic performance, the
activation of the stigma of inferiority also leads to increases in blood pressure (Blascovitch et
al. 2001). Similarly, Taylor and colleagues have found a positive association between
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internalized racism and alcohol consumption and psychological distress among African
Americans (Taylor et al. 1991; Taylor and Jackson 1990, 1991). Other recent research indicates
that high levels of internalized racism are associated with increased risk of overweight or
abdominal obesity among black women in the Caribbean (Tull et al. 1999; Chambers et al.
2004; Butler et al. 2002), and with waist circumferences, diastolic blood pressure and fasting
glucose among black women but not men in Africa (Tull et al. 2007). Racial stereotypes are
only one source of self-stereotyping. Their influence needs to be combined with other sources
of stigmatization, especially those that are more likely to be prevalent among socially
disadvantaged populations. For example, there are elevated rates of obesity in many racial
minority populations and evidence of both a stigma linked to obesity and discrimination
targeted at overweight individuals (Carr and Friedman 2005). Future research needs to explore
the extent to which elevated health risks are located at multiple intersections of stigmatization
and discrimination. Understanding how experiences of racial discrimination relate to
internalized racism and combine to affect health is also important (Carter 2007).

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Williams and Mohammed Page 18

Understanding how discrimination might affect health

Much current research on discrimination and health gives scant attention to the mechanisms
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and processes by which this association might exist. The stress literature indicates that stress
affects health through three principal pathways (Cohen et al. 1995). First, exposure to stress
can give rise to negative emotional states. These responses can generate psychological distress
that adversely affects health. Second, behavioral coping responses to manage stress can lead
to the initiation of unhealthy behaviors such as tobacco use and alcohol abuse, the
disengagement from health activities such as sleep and exercise and the neglect of adherence
to medical regimens. Third, both the psychological and behavioral responses to acute and
chronic stressors can lead to structural and functional changes in multiple physiological
systems, including the neuroendocrine, autonomic, and immune systems. These changes in
physiology and behavior can lead to changes in health. Importantly, stressors, including
discrimination can play a role in the onset, progression, and severity of illness. Studies of
discrimination and health need to devote greater thought to the conditions under which
particular aspects of discrimination are more or less likely to affect specific points of the disease
continuum.

Too often there is little consideration to identifying or thinking about the exposure and lag
times that would be necessary for a relationship to exist between exposure to discrimination
and subsequent illness. Most chronic illnesses such as cancer, CHD, diabetes, and hypertension
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develop over many years and are often diagnosed long after the disease process was initiated.
Accordingly, recent exposure to stressors, including discrimination, should not be related to
the onset of these conditions. At the same time, because stress can impact the course of disease,
it is important to consider how stress might affect the trajectory of an illness. This is especially
important given the large racial and SES disparities in the progression of disease. As noted
earlier, some recent studies have begun to pay attention to the role of discrimination in the
management of chronic illness, healthcare seeking behaviors and in adherence to medical
treatment. This is a very promising area in the study of discrimination and chronic disease and
is consistent with the literature on stress that indicates that one of the important ways in which
stress affects health is by shaping behavioral management of disease and leading to particular
health behaviors that can have negative health consequences (Cohen et al. 2007). In future
research, increased attention should be given to outcomes that capture the management, course,
progression, severity, and recurrence of illness.

The stress literature also suggests that the types of stressors and the aspects of stress that may
be important in determining the risk of getting an illness may be different from those aspects
that are determinants of the progression, course, and severity of the illness. That is, the factors
that are linked to the onset of disease may be different from those that overwhelm the body’s
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defenses in coping with illness. The distinction between chronic and acute discrimination may
be important for the underlying pathways by which discrimination-induced stress can lead to
disease. As with the general literature on stress, acute experiences of discrimination may trigger
acute episodes of illness while chronic discrimination may exacerbate existing disease
processes (Bhattacharyya and Steptoe 2007). In the absence of coronary disease, for example,
severe emotional distress from acute stress can trigger acute cardiovascular responses and
events that can lead to cardiovascular dysfunction. On the other hand, chronic stressors can
accelerate the atherosclerotic processes and lead to more rapid progression of disease (Brotman
et al. 2007). Similarly, mental health research reveals that major stressful life events (that
require a lot of change in usual activities) lead to the onset of psychopathology, while minor
stressful experiences play a role in the recurrence and severity of psychopathology
(Dohrenwend 2006). Future research on discrimination and health needs to pay greater
attention to matching the measure of discriminatory experience with the presumed disease
process.

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Williams and Mohammed Page 19

Research is also needed to elucidate the linkages between experiences of discrimination and
processes of illness. Ackerman et al. (2002) examined the role of life events in exacerbating
episodes of multiple sclerosis (MS). They followed 23 women with MS for a year and
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conducted a weekly assessment of stress. They found that life events served to rapidly
precipitate the relapse and the progression of disease, occurring an average of 14 days before
the exacerbation of MS. The study also found that a broad range of stressors were equally
associated with the processes of exacerbating the disease. This type of intensive study can serve
as a useful model for future research that can shed light on the pathways from discrimination
to health.

Future research on discrimination and health could also profitably focus its attention on those
outcomes where prior research has documented that stress in general is linked to health. It is
not reasonable to expect to find effects of discrimination on health in areas where the stress
literature has not shown an effect of stress. Stam (2007) has identified five physiological
categories where severe stress has been shown to affect intermediate physiological symptoms.
These are: the neuroendocrine system, the cardiovascular system (increased heart rate and
blood pressure responses), the gastrointestinal system (gastrointestinal ulcers, irritable bowel
syndrome), pain sensitivity and chronic pain and immune function (suppressed immunity).
Brotman et al. (2007) also indicate that components of the metabolic syndrome are promising
places to look for the effects of stress on cardiovascular disease.
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Personal and social factors and discrimination

Research on discrimination and health should also attend to the personal & situational factors
that might affect the underlying processes. Recent studies suggest that social factors can affect
the prevalence and the impact of the discrimination. Borrell et al. (2006) found a positive
association between perceived discrimination and SES. However, the larger literature is mixed
on this topic (Paradies 2006). Pearlin et al. (2005) emphasize that the consequences of a stressor
may vary by SES even if the prevalence of the stressor does not. Inadequate attention has been
given to examining interactions between discrimination and SES. The expected patterns are
unclear. Discrimination could be more severe for low SES groups because it may be harsher,
more easily legitimized and invisible, or it could be more impactful for high SES groups
because it could be perceived as a threat to their status (Jackson et al. 2006). Some limited
evidence is consistent with higher costs of discrimination among high SES blacks (Forman
2003), but this finding deserves replication.

Gender is another social variable that might affect the relationship between discrimination and
health. Consistent with the view that black men are more likely to be targets of discrimination
than black women because of gendered stereotypes that view them as more threatening, men
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tend to report higher levels of discrimination than women (Carter 2007). Gender differences
in the level and consequences of a stressor can be evident in opposite directions. For example,
men report higher levels of exposure to traumas but PTSD is more prevalent in women (Stam
2007). One recent study found that gender moderated the association between discrimination
and anxiety but not depression (Banks and Dracup 2006) while another found that the
association between discrimination and physical and mental health was stronger for women
than for men (Borrell et al. 2006). It is also important to explore the intersections of race, class
and gender. One study found that race-related stress had larger negative effects on middle class
than working class men, suggesting that the additional resources of the middle class did not
protect them from the negative effects of stressors (Pieterse and Carter 2007).

The shade of skin color (or skin tone) is another marker of social status and a potential predictor
of exposure to discrimination that has received inadequate research scrutiny (Krieger 1999).
Research has long indicated that skin tone is a marker of social status and an important predictor

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Williams and Mohammed Page 20

of access to socioeconomic opportunities and resources within the black population with the
associations being stronger for women than for men (Keith and Herring 1991). Prior research
has shown that skin tone is also a marker for discrimination, with darker skinned blacks
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reporting higher levels of discrimination than their lighter skinned peers (Keith and Herring
1991; Carter 2007). Similar patterns have been observed among Hispanics (Arce et al. 1987),
and Jews (Kraus and Koresh 1992). It is not clear though, if this association exists in all
contexts. For example, in the CARDIA study of African American young adults, skin color
was unrelated to reports of discrimination (Borrell et al. 2007). Insufficient research attention
has been given to the relationship of skin color to discrimination in recent research that would
allow conclusions regarding either secular change in the association over time, or the
identification of the conditions under which particular patterns are more or less likely to be
evident. Some evidence indicates that skin tone continues to matter for the earnings of African
Americans (Goldsmith et al. 2007), but it is unclear if there have been secular changes in its
role as a marker for discrimination. Future research needs to examine the extent to which
multiple social statuses combine to affect both the levels of exposure to discrimination and the
effects that discrimination can have on health.

There is a broad range of personal and situational factors that are important in determining
vulnerability and resilience to stressors. A full discussion of these is beyond the scope of this
paper (see paper by Brondolo, this issue). However, understanding the complex ways in which
psychosocial stressors get into the body to affect health will require future research to attend
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to and understand the large individual variation that exists in response to stressor exposure.
There is broad recognition in the stress literature that the effects of the experience of a particular
stressor combines with factors such as the presence of prior childhood and adult traumatic
experiences, levels of social support, feelings of helplessness and perceived control, a family
history of psychiatric disorders, psychological and behavioral coping responses, genetic
vulnerability, and a range of other personal factors (Yehuda et al. 2005; Stam 2007; Baum et
al. 1993; Carter 2007). These factors can directly mediate the negative effects of stressor
exposure or interact with stress to buffer or exacerbate its effects on health. Research in the
area of perceived discrimination and health needs to assess the role of these vulnerability and
resilience factors.

Conclusions
The research on discrimination and health is continuing to grow rapidly. Although the
discrimination variable has been operationalized in a variety of ways, the consistency of an
inverse association between discrimination for an increasingly broad range of health outcomes,
across multiple population groups in a wide range of cultural and national contexts is
impressive, and lends credibility to the plausibility of perceived discrimination as an important
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emerging risk factor for disease. This paper has described many of the limitations of this work
and outlined an ambitious research agenda so that the next generation of studies could provide
more definitive evidence on the conditions under which exposure to discrimination can lead
to changes in health status. It would also enhance our scientific understanding of the underlying
mechanisms and processes that may be at work. Our review finds that failure to
comprehensively and accurately characterize perceived discrimination and appropriately
assess its association with health will lead to erroneous conclusions about the underlying
relationship.

The research reviewed also raises larger questions for future research and policy regarding
health and its determinants. The accumulating evidence emphasizes that health policy, across
multiple societies needs to encompass the legacies of racial and ethnic inequality and the levels
of intolerance, incivility and anti-immigrant sentiment. These factors appear to matter a lot for
the health of targeted groups and as such require greater attention as a focus of health policy.

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Williams and Mohammed Page 21

Racism and ethnocentrism may not be inevitable. In the U.S., there have been marked declines
in racial prejudice and discrimination in the last several decades that have resulted from a broad
range of interventions (Schuman et al. 1997). However, there is still considerable opportunity
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to improve relations among population groups defined by race, ethnicity, migration history and
other stigmatized social statuses. There is also the need to more seriously begin to provide
targeted relief to individuals suffering from exposure to discrimination. One recent study
provided the sobering finding that a written disclosure intervention that has been shown to be
successful in improving health outcomes such as immune functioning among persons exposed
to various stressors was not effective when applied to persons dealing with racial discrimination
(Stetler et al. 2006). This raises the possibility that conventional stress management strategies
may not be effective in relieving the personal suffering linked to racial discrimination.

As a strategy for health improvement, more systematic research attention needs to be given to
expanding our knowledge of the individual and especially organizational interventions that can
be effective in reducing the levels, determinants and consequences of interpersonal and
institutional discrimination (Paradies 2005). Moreover, there is substantial progress yet to be
made in dismantling the institutional structures, processes, and policies that undergird societal
racism. As research continues to accumulate evidence that perceived discrimination can lead
to adverse changes in health, such efforts are an increasingly necessary component of
comprehensive approaches to improving the health of all in racialized societies.
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Acknowledgments
Preparation of this paper was supported in part by Grant R01 MH 59575 from the National Institute of Mental Health
(D.R.W), Grant 3 U-01 HL 087322-02S1, a Research Supplement to U-01 HL 87322-02 from the National Heart Lung
and Blood Institute (S.A.M.) and by the John D. and Catherine T. McArthur Foundation Research Network on
Socioeconomic Status and Health (D.R.W). We wish to thank Steven Beeber and Gabriel Sirota for assistance with
preparing the manuscript and Manuela Costa for assistance with the research.

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Table 1

Published research on discrimination and health in PubMed, 2005–2007a

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Study Sample size Design Outcome variables Findings

1. Mental health
Banks et al. (2006) 570 Blacks Cross-sectional Anxiety & depressive Positive association
symptoms
Beiser and Hou 647 SE Asian refugees Cross-sectional Depressive symptoms Positive association
(2006)
Bhui et al. (2005) 2054 UK workers Cross-sectional Anxiety & depression Positive association
Birman et al. 269 Soviet immigrant teens in US Cross-sectional Russian identity Positive association
(2005) American identity Inverse association
Brody et al. (2006) 714 Black adolescents Longitudinal Conduct problems & Positive association
depressive symptoms
Brook et al. 210 Black and Puerto Rican Cross-sectional Rebellious behavior Positive association
(2006a) elementary kids
Brondolo et al. 420 Blacks & Latinos Cross-sectional Emotions of threat, harm, & Positive association
(2005) anger
Broudy et al. 113 Multiethnic adults Cross-sectional Daily moods (anger, sadness Positive association
(2007) & nervousness)
Bynum et al. 247 Black freshmen Cross-sectional Psychological distress Positive association
NIH-PA Author Manuscript

(2007)
Crouter et al. 218 Mexican American families Cross-sectional Depressive symptoms Positive association
(2006)
Dyrbye et al. 3,080 U.S. medical students Cross-sectional Burnout, depressive Positive association
(2007) symptoms, low QOL
Gee et al. (2006b) 666 U.S. blacks, black & Latino Cross-sectional Mental Health Inverse association
immigrants
Gee et al. (2007b) 2,047 Asian American adults Cross-sectional Past year mental disorders Positive association
Greene et al. 136 High school students Longitudinal Depressive symptoms self- Positive association
(2006) esteem Inverse association
Self-esteem
Karlsen et al. 3,446 from 5 UK ethnic immigrants Cross-sectional Psychosis Positive association
(2005) Anxiety or depressive Positive association
disorder
Khaylis et al. 91 Undergrad students Cross-sectional PTSD symptoms Positive association
(2007)
Lam (2007) 122 Vietnamese college students Cross-sectional Depression & anxiety Positive association
symptoms
Lam et al. (2005) 1,451 Teens in Hong Kong Cross-sectional Depressive symptoms Positive association
NIH-PA Author Manuscript

Life satisfaction & purpose Inverse association

Lincoln et al. 4,915 African Americans & Cross-sectional Depressive symptoms Conditional association
(2007) Caribbean Blacks
Major et al. (2007) 3 Samples of Latino students (n = Cross-sectional Self-esteem Inverse association
191)
Miller and Travers 208 UK minority ethnic teachers Cross-sectional Psychological symptoms Positive association
(2005) (GHQ) Inverse association
Job satisfaction
Montgomery and 131 Middle Eastern refugees in Cross-sectional Internalizing symptoms Positive association
Foldspang (2007) Denmark Externalizing symptoms No association
Noh et al. (2007) 180 Adult Korean immigrants, Cross-sectional Positive affect Inverse association
Toronto Depressive symptoms Positive association
Oppedal et al. 1,275 Immigrant 10th graders in Cross-sectional Psychiatric problems Positive association
(2005) Norway

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Study Sample size Design Outcome variables Findings

Pantzer et al. 1,246 Native and immigrant Cross-sectional Health related quality of life Inverse association
(2006) adolescents in Spain
NIH-PA Author Manuscript

Pole et al. (2005) 668 Hispanic, white and black police Cross-sectional PTSD symptoms Positive association
officers
Poyrazli and 439 International & U.S. college Cross-sectional Homesickness Positive association
Lopez (2007) students
Romero et al. 519 Latino & non-Latino teens Cross-sectional Depressive symptoms, drug Positive association
(2007) use & violence
Salvatore and 250 University students Laboratory Cognitive functioning Inverse association
Shelton (2007)
Schulz et al. 700 Black women Cross-sectional Depressive symptoms Positive association
(2006b)
Sheridan (2006) 222 British Muslims Cross-sectional Depressive symptoms Positive association
Siefert et al. 824 Black mothers Cross-sectional Probable depression Positive association
(2007)
Simons et al. 332 Black teen males Longitudinal Violent delinquency Positive association
(2006)
Smokowski and 323 Latino teens Cross-sectional Internalizing problems and Positive association
Bacallao (2007) low self-esteem
Steffen and 168 Hispanic-American immigrants Cross-sectional Depressive symptoms Positive association
Bowden (2006) Sleep disturbance Positive association
NIH-PA Author Manuscript

Stevens et al. 1,127 Moroccan immigrant teens in Cross-sectional Externalizing behaviors Positive association
(2005a) Netherlands
Stevens et al. 1,127 Moroccan immigrant teens in Cross-sectional Internalizing problems Positive association
(2005b) Netherlands
Umaña-Taylor 273 Latino adolescents Cross-sectional Depressive symptoms Positive association
and Updegraff
(2007)
Utsey and Hook 215 Black college students Cross-sectional Psychological distress Positive association
(2007)
Utsey et al. (2006) 323 U.S. black adults Cross-sectional Quality of life Conditional association
Veling et al. 459 Ethnic minorities in The Cross-sectional Incidence of psychotic Positive association
(2007) Netherlands disorders
Vines et al. (2006) 476 Black women Cross-sectional Negative emotions Positive association
Wadsworth et al. 626 Blacks, whites, & Bangladeshis Cross-sectional Psychological distress Conditional association
(2007)
Wagner and 120 Diabetic blacks Cross-sectional Depression Positive association
Abbott (2007)
Waltermaurer et 88 Black women Cross-sectional Intimate partner violence Positive association
al. (2006)
NIH-PA Author Manuscript

Wamala et al. 33,328 Swedish adults Cross-sectional Psychological distress Positive association
(2007b)
Yoder et al. (2006) 212 American Indian youth Cross-sectional Suicidal ideation Positive association
2. Blood pressure/hypertension
Brown et al. 3,300 Multi-ethnic women Cross-sectional Systolic & diastolic BP No association
(2006)
Clark and Gochett 217 Black youth Cross-sectional Blood pressure Conditional association
(2006)
Clark (2006a) 234 Black high schoolers Cross-sectional Systolic & diastolic BP Conditional association
Cozier et al. 2316 Black women Longitudinal Hypertension incidence Conditional association
(2006)
Davis et al. (2005) 356 Black adults Cross-sectional Hypertension Conditional association

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Study Sample size Design Outcome variables Findings

Matthews et al. 207 Black & white teens Cross-sectional Ambulatory blood pressure Conditional association
(2005)
NIH-PA Author Manuscript

Peters (2006) 162 Blacks Cross-sectional Chronic stress emotions Positive association
Blood pressure No association
Peters et al. (2007) 145 Black hypertensive patients Cross-sectional Blood pressure Positive association
Satisfaction with care Inverse association
Roberts et al. 1,110 Middle-aged blacks Cross-sectional Hypertension Conditional association
(2007)
Ryan et al. (2006) 666 U.S. blacks, blacks & Latino Cross-sectional Physical health Inverse association
immigrants Systolic pressure U-shaped association
Diastolic pressure No association
3. Reactivity
Clark (2006b) 110 Black college women Lab experiment Vascular reactivity Positive association
Clark et al. (2006) 72 black men Lab experiment Cardiovascular reactivity Positive association
Clark et al. 153 Black youth Lab experiment Large arterial elasticity Conditional association
(2006a)
King (2005) 115 Black college women Lab experiment Affective stress reactions Positive association
Lepore et al. 80 black & white women Lab experiment Cardiovascular reactivity Positive association
(2006)
Merritt et al. 73 Normotensive black men Lab experiment Cardiovascular reactivity Positive association
NIH-PA Author Manuscript

(2006)
Richman et al. 165 Normotensive black & white Lab experiment Cardiovascular reactivity Positive association
(2007) adults
Thomas et al. 122 Employed blacks & whites Lab experiment Reactivity to phenylephrine Positive association
(2006)
4. Other physical health
Borrell et al. 1,722 Blacks Cross-sectional Self-reported health (SF- 12) Inverse association
(2006) Depressive symptoms (CES- Positive association
D)
Gee et al. (2007a) 2,095 Asian Americans Cross-sectional Chronic health conditions Positive association
Gee et al. (2006a) 2,241 Filipino Americans Cross-sectional Chronic health conditions Positive association
Harris et al. 4,108 Maori & 6,269 Europeans in Cross-sectional 4 self-reported measures of Positive association
(2006a) New Zealand ill health
Harris et al. 12,500 Adults in New Zealand Cross-sectional 5 measures of self-reported Positive association
(2006b) ill health
Larson et al. 639 Aboriginal & other Australians Cross-sectional Self-reported poor physical Positive association
(2007) & mental health
Lauderdale (2006) 15,064 Arab women Cross-sectional Low birth weight and Positive association
prematurity
NIH-PA Author Manuscript

Lewis et al. (2006) 181 Black women Longitudinal Coronary artery calcification Positive association
Locher et al. 1,000 Elderly adults Cross-sectional Nutritional risk Conditional association
(2005)
Moody-Ayers et 42 Diabetic blacks Cross-sectional Glycosylated hemoglobin No association
al. (2005) Self-rated health No association
Piette et al. (2006) 810 Adult diabetes patients Cross-sectional Hemoglobin A1c Positive association
Physical symptom burden Positive association
Poor physical functioning Positive association
(SF-12)
Schulz et al. 343 Black women Longitudinal Symptoms of depression Positive association
(2006a) Self-rated health Inverse association
Sellers et al. 399 Well-educated black men Cross-sectional Physical health No association
(2006) Mental health Inverse association

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Williams and Mohammed Page 37

Study Sample size Design Outcome variables Findings

Stetler et al. 48 Black participants Longitudinal Antibody response to flu Inverse association
(2006) vaccine
NIH-PA Author Manuscript

Sujoldzic et al. 1,282 Immigrant teens from Bosnia Cross-sectional Health problems Positive association
(2006) and Herzegovina residing in Bosnia, Psychological well-being Inverse association
Croatia or Austria
Taylor et al. 49,161 Black women Longitudinal Breast cancer incidence Positive association
(2007)
Thomas et al. 93 Employed men & women Cross-sectional Sleep stage 4 Inverse association
(2006) Physical fatigue Positive association
Vines et al. (2007) 447 Black women (35– 49 years) Cross-sectional Waist-hip ratio Inverse association
Wise et al. (2007) 22,002 U.S. black women Longitudinal Incidence of uterine Positive association
leiomyomata (fibroids,
myomas)
Young et al. 1,008 Illicit drug users Cross-sectional Mental health Inverse association
(2005) Chronic conditions Positive association
Zamboni and 174 Black gay/bisexual men Cross-sectional Sexual problems Positive association
Crawford (2007)
5. Health care utilization
Adegbembo et al. 924 Low-income blacks & whites Cross-sectional Health care trust Positive association
(2006)
Banks and Dracup 61 Blacks with MI Cross-sectional Delay in seeking treatment No association
NIH-PA Author Manuscript

(2006)
Bazargan et al. 287 Black and Latino adults Cross-sectional Alternative care use as Positive association
(2005) substitute for conventional
care
Benkert et al. 145 Low-income blacks Cross-sectional Satisfaction with care Inverse association
(2006)
Casagrande et al. 1,408 Blacks & whites Cross-sectional Delays in seeking medical Positive association
(2007) care Positive association
Non-adherence to medical
care
Chen et al. (2005) 3.884 adults Cross-sectional Preferences for same race Positive association
physician
Dailey et al. 1,229 Black and white women Cross-sectional Mammography screening No association
(2007)
Etowa et al. (2007) 237 Black Canadian women Cross-sectional Access to healthcare Inverse association
Facione and 817 Latino, black & white women Cross-sectional Non-adherence to cancer Positive association
Facione (2007) screening & fewer provider
visits
Fowler-Brown et 3,694 Black & white rural southern Cross-sectional Satisfaction with care Inverse association
al. (2006) adults Preventative services use No association
NIH-PA Author Manuscript

Hoyo et al. (2005) 144 Adult black women Cross-sectional Adherence to pap smear No association
screening
Jang et al. (2005) 230 Korean elderly Cross-sectional Satisfaction with care Inverse association
Malat and 1,189 Blacks Cross-sectional Preference for same race Positive association
Hamilton (2006) physician
Malat and van Ryn 1,189 Blacks Cross-sectional Preference for same race Positive association
(2005) physician
Nápoles-Springer 163 Blacks, Latinos & whites Cross-sectional Perceptions of the quality of Inverse association
et al. (2005) medical encounters
Sohler et al. 523 Adults Cross-sectional Poor quality of healthcare Positive association
(2007)
Trivedi and 54,968 Respondents Cross-sectional Received: cholesterol test, Inverse association
Ayanian (2006) eye exam, hemoglobin A1c No association
& flu shots

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Williams and Mohammed Page 38

Study Sample size Design Outcome variables Findings

Received: aspirin, PSA test
NIH-PA Author Manuscript

Van Houtven et al. 545 Black, Latino & white adults Cross-sectional Delay of filling prescriptions Positive association
(2005) Delay of treatments Positive association
Wamala et al. 31,851 Swedish adults Cross-sectional Refraining from seeking Positive association
(2007a) treatment
6. Substance use & health behaviors
Bennett et al. 2,129 Black college students Cross-sectional Tobacco use Positive association
(2005)
Borrell et al. 1,507 Blacks & 1,813 whites Cross-sectional Lifetime crack, speed, heroin No association
(2007) Alcohol, tobacco use Positive association
Lifetime cocaine & Positive association
marijuana
Brook et al. 731 South African teens Cross-sectional Cigarette smoking Positive association
(2006b)
Choi et al. (2006) 2,082 Middle school (multi & Cross-sectional Ever substance use & Positive association
monoracial) frequency Positive association
Violent behavior
Gee et al. (2007a) 2,217 Filipino Americans Cross-sectional Prescription medication use Positive association
Illicit drug use Positive association
Alcohol dependence Positive association
Gibbons et al. 889 Black families Longitudinal Subsequent drug use Positive association
(2007)
NIH-PA Author Manuscript

Kalichman et al. 2,122 Black and Coloured South Cross-sectional HIV risk behavior Positive association
(2006) Africans
Krieger et al. 159 Blacks, 249 Latinos & 208 Cross-sectional Cigarette smoking Positive association
(2005) whites Psychological distress Positive association
Landrine et al. 1,569 Black, Latino, Asian, and Cross-sectional Cigarette smoking & Positive association
(2006) White adults psychiatric symptoms
Terrell et al. 134 Black adolescents Cross-sectional Alcohol consumption Positive association
(2006)

a
Conditional association = discrimination is unrelated to health in the overall sample, but an association exits only for some sub-group
NIH-PA Author Manuscript

J Behav Med. Author manuscript; available in PMC 2010 February 14.


Very Low Birthweight in African American Infants:
The Role of Maternal Exposure to Interpersonal
Racial Discrimination
| James W. Collins Jr, MD, MPH, Richard J. David, MD, Arden Handler, DrPH, Stephen Wall, MD, and Steven Andes, PhD
It has long been recognized that African
American infants are more than twice as
likely as White infants to die in their first year
of life.1,2 Reflecting the public health rele-
vance of this phenomenon, Healthy People
2010 calls for the elimination of the racial
disparity in infant mortality rates.3 Infant
birthweight is a primary determinant of infant
mortality risk. The approximately 1% of
births occurring at very low birthweight
(VLBW; < 1500 g), pathological in all popula-
tions,1,4,5 accounts for more than half of the
neonatal deaths and 63% of the Black–White
gap in infant mortality in the United States.4
An extensive literature has treated pregnancy
as a condition influenced by proximal events
and has been unable to delineate the mecha-
nisms underlying African American infants’
threefold greater rate of VLBW.6–14 A seminal
study by Kleinman and Kessel6 found not
only a persistent but a widening racial gap in
the incidence of VLBW infants as sociodemo-
graphic risk declines (i.e., VLBW risk declines
as socioeconomic status increases). Another
study found that in a prepaid health plan, the
racial disparity in the rates of VLBW per-
sisted among college-educated mothers who
received adequate prenatal care.7 Behavioral
risk factors during pregnancy—cigarette smok-
ing and alcohol and illicit drug usage—also
have a negligible impact on the racial gap.14
Numerous epidemiological studies have found
that the racial differential in the rate of
VLBW infants exists among women who re-
side in nonimpoverished neighborhoods.10–13
New conceptual models have been pro-
posed to elucidate the contribution of
chronic stress to preterm (< 37 weeks) deliv-
ery and consequent VLBW risk.15–17 Rich-
Edwards et al.16 speculated that chronic
stress from maternal lifetime exposure to in-
terpersonal racism is a risk factor for infant
VLBW. Misra et al.17 proposed that social
2132 | Research and Practice | Peer Reviewed | Collins et al.
RETURN TO TABLE OF CONTENTS
 RESEARCH AND PRACTICE 
Objectives. We determined whether African American women’s lifetime expo-
sure to interpersonal racial discrimination is associated with pregnancy outcomes.
Methods. We performed a case–control study among 104 African American
women who delivered very low birthweight (<1500 g) preterm (<37 weeks) infants
and 208 African American women who delivered non–low-birthweight (> 2500g)
term infants in Chicago, Ill.
Results. The unadjusted and adjusted odds ratio of very low birthweight in-
fants for maternal lifetime exposure to interpersonal racism in 3 or more domains
equaled 3.2 (95% confidence intervals=1.5, 6.6) and 2.6 (1.2, 5.3), respectively. This
association tended to persist across maternal sociodemographic, biomedical,
and behavioral characteristics.
Conclusions. The lifelong accumulated experiences of racial discrimination by
African American women constitute an independent risk factor for preterm
delivery. (Am J Public Health. 2004;94:2132–2138)
(i.e., socioeconomic status) factors are ante- A causal association between African
cedent to both psychosocial (i.e., stress, social American women’s exposure to chronic stress
support) factors and biomedical (i.e., health from interpersonal racism and infant VLBW
behaviors, preexisting diseases) factors; the is biologically plausible. Wadhwa et al.22
latter are in turn risk factors for infant showed that chronic maternal exposure to
VLBW. Hogue et al.15 proposed the classic stress—through maternal cardiovascular,
host (i.e., pregnant women), environment immune/inflammatory, and neuroendocrine
(i.e., chronic social stressors), and agent (i.e., processes—is detrimental to infants’ birth-
immediate emotional or physical stressors) weight. Moreover, psychophysiological stress
triangle of epidemiological causality.5 is likely to accelerate the release of corti-
Chronic stress is a more prominent feature cotropin-releasing hormone, which initiates
in the daily lives of African American women a cascade of events leading to preterm deliv-
than in the daily lives of White women.18 Al- ery.16,22 Consistent with the larger literature
though there have been several studies on the on stress, clinical studies show that exposure
relation between chronic stress and infant to racial stressors leads to physiological reac-
birthweight,19–21 few studies have specifically tivity.23–27 African American women who
focused on the relation between women’s reg- were exposed to what they perceived as racial
ular (ranging from a few times per year to bias and internalized their responses to unfair
nearly every day) exposure to racial discrimi- treatment had a fourfold greater risk of hy-
nation—a nonrandom and race-related source pertension.23 In another study, the viewing of
of stress—and infant VLBW.18 To the extent racist situations was associated with a signifi-
that population differences in chronic stress cant rise in blood pressure that correlated
from lifetime exposure to interpersonal racial with the African American subjects’ responses
discrimination underlie the observed racial on the Framington Anger Scale.24 Jones et
differential in the rate of VLBW infants, one al.25 also reported significant changes in heart
would expect an association between this ex- rate, digital blood flow, and facial muscle ac-
posure and VLBW among African Americans. tivity in African American women who en-
American Journal of Public Health | December 2004, Vol 94, No. 12

countered social situations that included bla-
tant and more subtle forms of racism.
We therefore performed a case–control
study among a sample of urban African
Americans to determine the extent to which
women’s reported lifetime and pregnancy ex-
posure to interpersonal racial discrimination
is associated with VLBW births.
METHODS
Study Sample
African American mothers delivering at
Cook County Hospital and University of Chi-
cago Hospital in Chicago, Ill, between Novem-
ber 1, 1997, and October 31, 2000, were re-
cruited for this study. These hospitals serve
critically ill and healthy infants across a broad
range of socioeconomic status. Nevertheless,
approximately two thirds of the participants in
the study were Medicaid recipients.
The medical record was abstracted to de-
termine infants’ birthweight as defined by
nursing measurement, gestational age based
on physicians’ physical assessment of the
neonate, and maternal race as self-defined.
Case subjects were restricted to mothers of
singleton VLBW (< 1500 g) preterm (< 37
weeks) infants. Control subjects were re-
stricted to mothers of (1) critically ill singleton
non–low-birthweight (NLBW; > 2500 g),
term infants admitted to the neonatal inten-
sive care unit for ventilator management; and
(2) healthy singleton NLBW infants admitted
to the normal newborn nursery. We ap-
proached the mothers of all eligible VLBW
and critically ill NLBW infants. To ensure a
1:2 case-to-control ratio, we approached
mothers of healthy NLBW infants who most
approximated case infants with respect to
time and day of admission within each partic-
ipating hospital. We offered a $10 participa-
tion reward to all eligible subjects. Study per-
sonnel approached African American
mothers within 72 hours of their infants’ ad-
mission to the neonatal intensive care unit or
normal newborn nursery. We obtained in-
formed consent from the women before study
enrollment. Mothers of infants who expired
within 72 hours of birth were not requested
to complete the study questionnaire.
During the accrual period, 117 case subjects
and 234 control subjects were potentially eligi-
December 2004, Vol 94, No. 12 | American Journal of Public Health
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 RESEARCH AND PRACTICE 
ble. Of these, 3 case subjects and 5 control
subjects refused interviews; 4 case subjects
and 5 control subjects consented but failed to
arrive at 3 scheduled appointments; we were
unable to schedule interviews for 2 case sub-
jects and 16 control subjects. The infants of 4
case subjects expired within 72 hours of birth.
Thus, we obtained interview data for 104 case
subjects and 208 control subjects.
Study Questionnaire
Trained African American interviewers ad-
ministered a structured questionnaire in the
hospital. They collected data on mothers’ age,
education, marital status, parity, prenatal care
initiation, cigarette smoking, and alcohol use.
Using previously validated instruments, they
asked about lifetime and pregnancy exposure
to interpersonal racial discrimination.23,28 All
participants were asked their lifetime and
pregnancy exposure to interpersonal racial
discrimination in 5 domains: at work, getting
a job, at school, getting medical care, and get-
ting service at a restaurant or store.23 The
questions were formatted for yes or no an-
swers.23 We determined the distribution of re-
ported interpersonal racial discrimination in
each domain, 1 or more domains, and 3 or
more domains. Current or recently employed
participants were asked an additional 20
questions about their lifetime and past year’s
experiences with interpersonal racial discrimi-
nation at their primary place of employ-
ment.28 We empirically dichotomized re-
sponses after data collection into none (none
or less than once per year) and regularly (few
times per year, few times per month, at least
once a week, and nearly every day).
Statistics
We calculated the odds ratio and 95% confi-
dence intervals of exposure to measured risk
factors.29 Confidence intervals were estimated by
the Taylor series method.29 We used multivari-
able logistic regression (PROC LOGISTIC30) to
estimate the independent association of mater-
nal lifetime exposure to racism and VLBW.
RESULTS
There were minimal differences between
case subjects and control subjects (critically ill
and healthy) with respect to marital status, in-
Collins et al. | Peer Reviewed | Research and Practice | 2133
come, Medicaid status, prenatal care usage,
parity, and alcohol consumption (Table 1). A
slightly higher percentage of case subjects
were found among the older, more educated
women, and cigarette smokers (Table 1). When
women aged older than 30 years or those hav-
ing more than 12 years of education were
compared with all others, a significantly in-
creased association with VLBW was found
(χ2=4.8, P=.03 for age, χ2 =5.4, P=.02 for
education). The distribution of sociodemo-
graphic, biomedical, and behavioral character-
istics did not vary between critically ill and
healthy control subjects (data available from
authors by request).
Table 2 examines the relation between ma-
ternal exposure to interpersonal racism and
VLBW in 5 domains. With the exception of
the “getting medical care” domain, the odds
ratio of VLBW for maternal lifetime exposure
to interpersonal racial discrimination ex-
ceeded unity. The magnitude of the associa-
tion between racial discrimination and VLBW
was strongest in the “finding a job” and “at
work” domains. The odds ratio of VLBW for
maternal lifetime exposure to interpersonal ra-
cial discrimination in 1 or more domains was
1.9 (95% CI =1.2, 3.1). The odds ratio of
VLBW for maternal lifetime exposure to inter-
personal racial discrimination in 3 or more
domains was 3.2 (95% CI =1.5, 6.6), suggest-
ing a dose-response relation. In contrast, there
was no consistent association of VLBW with
incidents of perceived discrimination during
the pregnancy.
When case subjects were compared only
with critically ill control subjects, the odds ratio
for exposure to racial discrimination in 1 or
more and 3 or more domains equaled 1.9 (95%
CI=1.1, 3.2) and 3.4 (95% CI=1.4, 8.3), respec-
tively. When case subjects were compared
only with healthy control subjects, the odds
ratio for exposure to racial discrimination in 1
or more and 3 or more domains equaled 1.9
(95% CI=1.1, 3.4) and 3.0 (95% CI=1.3,
7.3), respectively. We further tested for the
presence of recall bias by comparing the fre-
quency of reported exposure to interpersonal
racial discrimination in the 2 control groups of
African American women with NLBW infants.
The odds ratio for exposure to racial discrimi-
nation in 1 or more and 3 or more domains
for critically ill (compared with well) control
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 RESEARCH AND PRACTICE 

TABLE 1—Sociodemographic, Biomedical, and Behavioral Characteristics of the Study 3 or more domains were 2.8 (95% CI =1.1,
Sample: Chicago, Ill, November 1, 1997–October 31, 2000 7.1) and 7.3 (95% CI =1.9, 28.9), respectively.
By contrast, for alcohol use and prenatal care
Percentage (No.) of Percentage (No.) Of Odds Ratio (95% categories, the racism effect was consistently
VLBW Cases (n = 104) NLBW Controls (n = 208) Confidence Interval)
stronger among women in the traditional high-
Maternal age, y risk sociodemographic, biomedical, and be-
< 20 27 (28) 31 (62) 1.1 (0.6, 2.1) havioral categories. Most important, 43 of the
20–24 25 (26) 31 (63) 1.0 48 odds ratios of VLBW for maternal lifetime
25–29 19 (20) 21 42) 1.2 (0.6, 2.3) exposure to interpersonal racial discrimination
≥ 30 28 (29) 17 (35) 2.0 (1.0, 3.9) across the measured traditional risk factors
Education, y were above unity; 95% confidence intervals
< 12 31 (31) 39 (77) 0.5 (0.3, 0.9) often included 1.
12 34 (34) 39 (77) 0.6 (0.3, 1.0) Seventy-six percent (n = 238) of women in
> 12 36 (36) 23 (46) 1.0 the study sample had worked outside the
Living arrangements home during their lifetime. Two thirds (n =
Married 23 (22) 15 (31) 1.0 163) of them were employed during their
Unmarried, living together 12 (11) 18 (36) 0.4 (0.2, 1.0) pregnancy. They worked an average of 35
Unmarried, not together 65 61) 67 (134) 0.6 (0.3, 1.2) hours per week. The leading employment
Income quartile, $a categories were cashiers (23%), clerks
1: < 5000 28 (20) 29 (31) 0.8 (0.3, 1.9) (13%), teachers (10%), laborers (10%), and
2: 5000–15 999 23 (16) 29 (31) 0.7 (0.3, 1.6) health care workers (8%). These 163
3: 16 000–30 999 27 (19) 23 (25) 1.0 (0.4, 2.3) women answered additional questions about
4: ≥ 31 000 23 (16) 19 (20) 1.0 specific scenarios with racial discrimination
Payment method
at their primary place of employment, either
Medicaid 62 (58) 68 (138) 0.8 (0.5, 1.2)
anytime during their lifetime (10 questions)
Other payments 38 (35) 32 (63) 1.0
or during the past year (10 questions). For
Prenatal care
each of the questions in which there were
Earlyb 69 (71) 61 (127) 1.0
sufficient responses for reasonably
Late or none 31 (32) 39 (81) 0.7 (0.4, 1.2)
stable rate calculations, the point estimates
Pregnancies, No.
for the association between regular (defined
1–3 86 (89) 85 (171) 1.0
as “few times/year,” “few times/month,” “at
≥4 14 (14) 15 (31) 0.9 (0.4, 1.7)
least once a week,” or “nearly everyday”) ex-
Cigarette smoking
posure and VLBW exceeded unity (Table 4).
Smoker 30 (31) 21 (43) 1.6 (1.0, 2.8)
The scenarios that had the strongest associa-
Nonsmoker 70 (72) 79 (163) 1.0
Alcohol consumption
tion with VLBW were “Because you are Af-
Yes 18 (19) 15 (32) 1.2 (0.7, 2.3) rican American, you feel as if you have to
No 82 (84) 85 (176) 1.0 work twice as hard” and “Whites often as-
sume that you work in a lower status job
Note. VLBW = very low birthweight; NLBW = non–low-birthweight. than you do and treat you as such.” The
a
For household income, 43% are missing data.
b
Defined as initiation in the first trimester. odds ratios were between 1.1 and 2.6, al-
though few were statistically significant.
Lastly, we performed multivariate logistic
regression analyses to further explore the in-
subjects were 1.0 (95% CI=0.6, 1.7) and 1.1 generally considered the optimal childbearing dependent association of maternal reported
(95% CI=0.4, 3.1), respectively. decade, whereas it was reduced or absent lifetime exposure to interpersonal racial dis-
Table 3 shows that the association between among teenaged women and women aged crimination and pregnancy outcome. When
maternal lifetime exposure to interpersonal older than 30 years. Similarly, the association maternal age, education, and cigarette smok-
racism and infant VLBW persisted across tra- between maternal exposure to interpersonal ing were included in logistic models, the ad-
ditional sociodemographic, biomedical, and racial discrimination and VLBW was strongest justed odds ratio of infant VLBW for mater-
behavioral risk categories; however, there was among women with more than 12 years of nal reported exposure to interpersonal racial
some evidence of effect modification. The ad- formal education. The odds ratios of infant discrimination in 1 or more domains was 1.7
verse effect of perceived discrimination was VLBW for college-educated women who re- (95% CI = 1.0, 9.2); the adjusted odds ratio
strongest among women aged 20 to 29 years, ported racial discrimination in 1 or more and of infant VLBW for maternal reported expo-

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 RESEARCH AND PRACTICE 

TABLE 2–Maternal Exposure to Interpersonal Racial Discrimination and Infant Very Low Birthweight

Reported Racial Discrimination Incidents

Lifetime This Pregnancy
Percentage (No.) Percentage (No.) Percentage (No.) Percentage (No.)
VLBW n = 104 NLBW n = 208 OR 95% CI VLBW n = 10 NLBW n = 2088 OR 95% CI

Finding a job 29 (30) 13 (25) 3.0 1.6, 5.4 2 (2) 1 (3) 1.3 0.2, 8.1
At work 24 (25) 14 (29) 2.0 1.1, 3.5 4 (4) 5 (10) 0.8 0.2, 2.6
At school 18 (19) 11 (22) 1.9 1.0, 3.7 2 (2) 2 (4) 1.0 0.2, 5.6
In public settings 37 (38) 29 (61) 1.4 0.8, 2.3 13 (14) 15 (31) 0.9 0.5, 1.8
Getting medical care 5 (5) 5 (11) 0.9 0.3, 2.7 4 (4) 2 (4) 1.6 0.4, 6.2
≥ 1 domains 56 (58) 40 (83) 1.9 1.2, 3.1 19 (20) 20 (42) 0.9 0.5, 1.7
≥ 2 domains 41 (32) 25 (41) 2.1 1.2, 3.8 6 (6) 4 (8) 1.5 0.5, 4.4
≥ 3 domains 30 (20) 12 (17) 3.2 1.5, 6.6 0 (0) 1 (2) ... ...

Note. VLBW = very low birthweight; NLBW = non–low-birthweight; OR = odds ratio; CI = confidence interval.

sure to interpersonal racial discrimination in 3
or more domains was 2.6 (95% CI = 1.2, 5.3).
DISCUSSION
Our study adds to the small but growing ev-
idence of a relation between African American
women’s exposure to interpersonal racial dis-
crimination and pregnancy outcomes. We
found that African American mothers who de-
livered VLBW preterm infants were more
likely to report experiencing interpersonal ra-
cial discrimination during their lifetime than
African American mothers who delivered
NLBW infants at term. Stratified analyses
showed that this association persisted across
the common risk categories for reproductive
health. In multivariate logistic regression mod-
els, the adjusted odds ratio of VLBW for Afri-
can American mothers who experienced inter-
personal racial discrimination in 1 or more
and 3 or more (compared with none) domains
equaled 1.7 and 2.6, respectively. Interestingly,
among African American women who worked
outside the home, those who gave birth to
VLBW infants were more likely to report ra-
cial discrimination in the workplace than were
the working mothers of NLBW infants. These
findings provide evidence that greater lifetime
exposure to racial discrimination among Afri-
can American women contributes to the racial
disparity in VLBW infants.
The conventional investigative approach to
the racial disparity in the rates of VLBW
births has been based on the implicit assump-
tion that there is a set of risk factors that dif-
fer in quantity between the races but exert
similar effects on African American and
White women. An extensive literature has
shown that established risk factors have mini-
mal impact on the rate of VLBW for African
Americans.6,7 Moreover, this conceptualiza-
tion does not take into account the nonran-
dom, pervasive, and multifaceted inequality
that is bound up in the historical context of
race, nor does it capture its effect on human
beings over time.18,31,32 Because African
American women are regularly exposed to
unique societal risk factors closely related to
race,18,31–33 restricting the search for such fac-
tors to a sample of African American women
seems reasonable. We used an interviewer-
administered closed-ended questionnaire to
capture the variability of lifetime exposure to
incidents perceived as racial discrimination
and describe its association with infant birth-
weight. The frequency of lifetime reported in-
cidents of interpersonal racial discrimination
in at least 1 domain was 40% among our
control subjects. If we take this frequency as
an accurate estimate for the general popula-
tion of urban African American women, then
exposure to perceived racial discrimination is
a common risk factor. This estimate is consis-
tent with published prevalence rates.34
Our data show that the magnitude of the
association between maternal reported life-
time exposure to racial discrimination and in-
fant VLBW was strongest in the “finding a
job” and “at place of employment” domains.
Concordant with this phenomenon, working-
class African American mothers of VLBW
preterm infants in our sample were more
likely to regularly experience specific epi-
sodes of interpersonal racism at their primary
place of employment than working-class Afri-
can American mothers of NLBW term in-
fants. These findings are consistent with the
limited literature showing a negative associa-
tion between pregnant African American
women’s psychosocial job strain and infant
birthweight.35 A recent study found that Afri-
can American women with high job strain
had infants with birthweights 273 grams less
than those with low-strain jobs or those who
did not work outside the home.35
Few published studies have explicitly ex-
amined the relation between maternal expo-
sure to racial discrimination and infant
birthweight.36,37 Using mailed questionnaire
data from the Black Women’s Health Study,
Rosenberg et al.37 recently reported a small
increase in preterm delivery among women
who reported lifetime experiences of racism,
particularly women with low levels of educa-
tion.7 In contrast, our study shows that the as-
sociation between maternal reported lifetime
exposure to interpersonal racism and infant
VLBW is strongest among college-educated
women. Because reporting discrimination
may adversely affect self-esteem and percep-
tions of control,38 differences in the method-
ology (i.e., mailed survey vs face-to-face inter-
views) used to assess lifetime incidents may
contribute to the dissimilar findings. Further

December 2004, Vol 94, No. 12 | American Journal of Public Health Collins et al. | Peer Reviewed | Research and Practice | 2135
 RETURN TO TABLE OF CONTENTS

 RESEARCH AND PRACTICE 

TABLE 3—Maternal Lifetime Exposure to Interpersonal Racial Discrimination and Infant Birthweight
by Selected Characteristics

Reported Racial Discrimination Incidents in Reported Racial Discrimination Incidents in

≥ 1 Domains (vs No Reported Discrimination) ≥ 3 Domains (vs No Reported Discrimination)
Percentage (No.) Percentage (No.) Percentage (No.) Percentage (No.)
VLBW n = 104 NLBW n = 208 OR 95% CI VLBW n = 104 NLBW n = 208 OR 95% CI

Maternal age, y
< 20 50 (14) 44 (27) 1.3 0.5, 3.2 13 (2) 15 (6) 0.8 0.2, 4.6
20–24 62 (16) 32 (20) 3.4 1.3, 8.9 33 (5) 4 (2) 10.8 1.8, 63.6
25–29 60 (12) 40 (17) 2.2 0.7, 6.5 43 (6) 14 (4) 4.7 1.1, 20.9
≥ 30 52 (15) 49 (17) 1.1 0.4, 3.0 33 (7) 18 (4) 2.3 0.5, 9.2
Education, y
< 12 39 (12) 34 (26) 1.2 0.5, 2.9 14 (3) 7 (4) 2.0 0.4, 9.8
12 53 (18) 39 (30) 1.8 0.8, 4.0 24 (5) 15 (8) 1.8 0.5, 6.4
> 12 75 (27) 52 (24) 2.8 1.1, 7.1 57 (12) 15 (4) 7.3 1.9, 28.9
Married 64 (14) 55 (17) 1.4 0.5, 4.4 56 (10) 22 (4) 4.4 1.0, 18.6
Living together 73 (8) 31 (11) 6.1 1.3, 27.3 25 (1) 11 (3) 2.8 0.2, 36.0
Not together 48 (29) 39 (52) 1.4 0.8, 2.6 16 (6) 10 (9) 1.7 0.6, 5.2
Income quartile, $a
1: < 5000 40 (8) 29 (9) 1.6 0.5 , 5.3 8 (1) 4 (1) 1.8 0.1, 32.0
2: 5000–15 999 75 (12) 39 (12) 4.8 1.2 , 18.2 50 (4) 14 (3) 6.3 1.0, 40.1
3: 16 000–30 999 47 (9) 48 (12) 1.0 0.3 , 3.2 29 (4) 13 (2) 2.6 0.4, 17.1
4: ≥ 31 000 69 (11) 80 (16) 0.6 0.1 , 2.5 55 (6) 56 (5) 1.0 0.2, 5.6
Payment method
Medicaid 50 (29) 37 (51) 1.7 0.9 , 3.2 22 (8) 11 (10) 2.4 0.9, 6.7
Other payment 64 (23) 45 (29) 2.1 0.9 , 4.9 38 (8) 13 (5) 4.3 1.2, 15.6
Prenatal care
Earlyb 52 (37) 42 (53) 1.5 0.8, 2.7 28 (13) 14 (12) 1.7 1.0, 5.7
Late or none 63 (20) 37 (30) 2.8 1.2, 6.6 37 (7) 9 (5) 3.1 1.5, 6.2
Pregnancies, No.
1–3 60 (53) 40 (68) 2.2 1.3, 3.8 32 (17) 13 (15) 3.2 1.5, 7.2
≥4 36 (5) 42 (13) 0.8 0.2, 2.8 25 (3) 5 (1) 6.0 0.5, 66.2
Cigarette smoking
Smoker 52 (16) 30 (13) 2.5 0.9, 6.4 21 (4) 14 (5) 1.6 0.4, 6.8
Nonsmoker 57 (41) 43 (70) 1.8 1.0, 3.1 34 (16) 11 (12) 4.0 1.7, 9.4
Alcohol consumption
Yes 68 (13) 34 (11) 4.1 1.2, 13.9 40 (4) 9 (2) 7.0 1.0, 48.0
No 52 (44) 41 (72) 1.6 0.9, 2.7 29 (16) 13 (15) 2.8 1.3, 6.1

Note. VLBW = very low birthweight; NLBW = non–low-birthweight; OR = odds ratio; CI = confidence interval.
a
Forty-three percent are missing data for household income.
b
Defined as initiation in the first trimester.

research is needed to determine whether the
inconsistencies reflect differences in unmea-
sured contextual variables.10,12,13,39–41
Our study provides empirical evidence sup-
porting the conceptual model proposed by
Rich-Edwards et al.16 in which African Ameri-
can women’s lifetime exposure to interper-
sonal racism is explicitly included as a chronic
stressor.16 Interestingly, we found no associa-
tion between maternal self-reported exposure
to interpersonal racial discrimination during
pregnancy and infant VLBW. However, the
prevalence of 1 or more reported incidents
during pregnancy among case subjects and
control subjects was low; moreover, the preva-
lence of 3 or more reported incidents during
pregnancy among subjects was essentially
nonexistent. Given the suspected strong asso-
ciation between reported incidents of interper-
sonal racial discrimination during pregnancy
and VLBW among the subgroup of low-income
African American mothers with high-risk be-
havioral characteristics,36 our study did not
have sufficient power to address the role of re-
ported incidents during pregnancy.
Our study had a number of important limi-
tations. First, because the experience of racial
discrimination is a complex and multidimen-
sional phenomenon, a more sensitive ques-
tionnaire may have led to better ascertain-

2136 | Research and Practice | Peer Reviewed | Collins et al. American Journal of Public Health | December 2004, Vol 94, No. 12
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 RESEARCH AND PRACTICE 

TABLE 4—Maternal Exposure to Interpersonal Racial Discrimination in the Workplace

and Infant Very Low Birthweight

Lifetime Past Year

Percentage Percentage Percentage Percentage
Specific Perceptions VLBW n = 53 NLBW n = 110 OR CI VLBW n = 53 NLBW n = 110 OR CI

Because you are African American, you are 19 12 1.7 0.7, 4.3 12 8 1.4 0.5, 4.2
assigned the jobs no one else will do.
You are treated with less dignity and respect 21 12 2.0 0.8, 4.7 23 11 2.3 1.0, 5.5
than you would be if you were White.
You are watched more closely than other 17 8 2.3 0.8, 6.1 10 8 1.3 0.4, 4.1
workers because of your race.
Racial jokes or harassment are directed at you. ... ... ... ... ... ... ... ...
Because you are African American, you feel as 28 17 1.9 0.9, 4.1 25 18 1.6 0.7, 3.5
if you have to work twice as hard.
Tasks that require intelligence are generally given 20 12 1.8 0.7, 4.6 14 11 1.3 0.5, 3.6
to Whites, while African-Americans get those
that don’t require much thought.
You are often ignored or not taken seriously by ... 6 ... ... ... 5 ... ...
your boss because of your race.
Whites often assume that you work in a lower 29 15 2.3 1.0, 5.1 32 15 2.6 1.2, 5.8
status job than you do and treat you as such.
A White coworker with less experience and ... 10 ... ... ... 9 ... ...
qualifications got promoted before you did.
When different opinions would be helpful, your 10 9 1.1 0.3, 3.3 ... 5 ... ...
opinion is not asked for because of your race.
Total positive responses
≥1 47 34 1.7 0.8, 3.5 49 32 2.0 1.0, 4.3
≥ 3 or more 26 16 1.7 0.7, 4.0 27 16 1.8 0.8, 4.4

Note. VLBW = very low birthweight; NLBW = non–low-birthweight; OR = odds ratio; CI = confidence interval; . . . = undefined (< 5 subjects).

ment of the exposure of chronic interpersonal
racism. However, the assessment of discrimi-
nation in multiple domains and the charac-
terization of regular exposure to discrimina-
tion in the workplace are strengths of the
instruments used in our study.23,28,38 In addi-
tion, the consistency of the elevated point
estimates derived from 2 independently con-
structed instruments suggests that we accu-
rately assessed exposure to interpersonal ra-
cial discrimination.23,28 Second, our findings
may have stemmed from a recall bias associ-
ated with the maternal anxiety associated
with the admission of her infant to a neona-
tal intensive care unit. However, we found no
difference in the prevalence of reported rac-
ism among control mothers of critically ill
NLBW infants (a cohort with anxieties simi-
lar to those of case subjects) and the control
mothers of healthy NLBW infants. Third,
interviewer bias could have also influenced
our results. However, the interviewers were
trained to collect data using a structured
questionnaire in an identical fashion for case
subjects and control subjects. They were also
blinded to the study hypotheses. Fourth, sam-
ple size considerations limited our ability to
fully address the association of racism and in-
fant VLBW across the full range of maternal
sociodemographic, biomedical, and behav-
ioral characteristics. Lastly, the results of our
study may be limited by the possible con-
founding of unmeasured variables closely re-
lated to interpersonal racial discrimination.41
Lifelong exposure to interpersonal racism is
unlikely to operate as a risk factor for preg-
nant women solely at the individual level,
but it also expresses the cumulative impact
of societal-level (i.e., institutional) racism ex-
posures on birth outcome.32,39 Our study
suggests that a mechanism by which institu-
tional racism affects female reproductive
health is likely to be found in the reported
incidents of racial discrimination in the
workplace. As such, interventions that tar-
get both the reported incidents of racial dis-
crimination in the workplace and the struc-
tural issues of race inequality that place a
large percentage of African American
women in conditions of severe income inse-
curity are needed to narrow the racial dis-
parity in infant VLBW.41
In conclusion, the reported lifelong accu-
mulated experiences of interpersonal racial
discrimination by African American women
constitute an independent risk factor for in-
fant VLBW.
About the Authors
James W. Collins Jr is with the Department of Pediatrics,
Children’s Memorial Hospital, Feinberg School of Medi-
cine, Northwestern University, Chicago, Ill. Richard J.
David is with the Department of Pediatrics, Cook County

December 2004, Vol 94, No. 12 | American Journal of Public Health Collins et al. | Peer Reviewed | Research and Practice | 2137

Hospital, University of Illinois Medical School, Chicago.
Arden Handler and Steven Andes are with the School of
Public Health, University of Illinois, Chicago. At the time
of the study, Stephen Wall was with the University of Chi-
cago Hospital, Chicago, Ill.
Requests for reprints should be sent to James W. Collins Jr,
Division of Neonatology, Children’s Memorial Hospital,
2300 Children’s Plaza, No. 45, Chicago, IL 60614 (e-mail:
jcollins@northwestern.edu).
This article was accepted May 6, 2004.
Contributors
J. Collins originated the study, led the writing, and su-
pervised all aspects of its implementation. R. David led
the analyses and supervised subject recruitment at
Cook County Hospital. A. Handler assisted with the
study and questionnaire development. S. Wall assisted
with the study and supervised subject recruitment at
the University of Chicago. S. Andes synthesized the
analyses and supervised data entry. All authors helped
to conceptualize ideas, interpret findings, and review
drafts of the article.
Acknowledgments
This study was funded by Chicago Community Trust to
J. W. Collins Jr.
Human Participant Protection
Institutional review board approval was obtained at
each hospital and participants provided written in-
formed consent.
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American Journal of Public Health | December 2004, Vol 94, No. 12
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American Journal of Obstetrics and Gynecology (2005) 192, 882–6

www.ajog.org

The Preterm Prediction study: Association between

maternal body mass index and spontaneous and
indicated preterm birth
Israel Hendler, MD,* Robert L. Goldenberg, MD, Brian M. Mercer, MD,
Jay D. Iams, MD, Paul J. Meis, MD, Atef H. Moawad, MD, Cora A. MacPherson, PhD,
Steve N. Caritis, MD, Menachem Miodovnik, MD, Kate M. Menard, MD,
Gary R. Thurnau, MD, Yoram Sorokin, MD

National Institute of Child Health and Human Development, Maternal-Fetal Medicine Units Network,
National Institutes of Health, Bethesda, Md

Received for publication June 18, 2004; revised August 31, 2004; accepted September 15, 2004

KEY WORDS Objective: The purpose of this study was to evaluate the relationship between prepregnancy
Maternal obesity maternal body mass index and spontaneous preterm birth and indicated preterm birth.
Spontaneous preterm Study design: This was a secondary analysis of the Maternal-Fetal Medicine Units Network,
birth Preterm Prediction study. Patients were classified into categories that were based on their body
Body mass index mass index. Rates of indicated and spontaneous preterm birth were compared.
Results: Five hundred ninety-seven (20.5%) of 2910 women were obese. Obese women had fewer
spontaneous preterm births at !37 weeks of gestation (6.2% vs 11.2%; P ! .001) and at !34
weeks of gestation (1.5% vs 3.5%; P = .012). Women with a body mass index of !19 kg/m2 had
16.6% spontaneous preterm birth, with a body mass index of 19 to 24.9 kg/m2 had 11.3%
spontaneous preterm birth, with a body mass index of 25 to 29.9 kg/m2 had 8.1% spontaneous
preterm birth, with a body mass index of 30 to 34.9 kg/m2 had 7.1% spontaneous preterm birth,
and with a body mass index of R35 kg/m2 had 5.2% spontaneous preterm birth (P ! .0001).
Indicated delivery was responsible for an increasing proportion of preterm births with increasing
body mass index (P = .001). Obese women had lower rates of cervical length !25 mm (5% vs
8%; P = .012). Multivariable regression analysis confirmed a lower rate of spontaneous preterm
birth in obese gravid women (odds ratio, 0.57; 95% CI, 0.39-0.83; P = .003).
Conclusion: Obesity before pregnancy is associated with a lower rate of spontaneous preterm birth.
Ó 2005 Elsevier Inc. All rights reserved.

Supported by grants from the National Institute of Child Health and Human Development: HD27917, HD27869, D27915, HD27860, HD27861,
HD21410, HD27889, HD21410, HD 27905, HD27889, HD21414, HD27889, HD19897 and HD36801.
Presented at the Society for Gynecologic Investigation annual meeting, March 22-27, 2004, Houston, Tex.
* Reprint requests: Israel Hendler MD, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Hutzel Hospital-Wayne
State University, 3990 John R Rd, Detroit, MI 48201.
E-mail: ihendler@med.wayne.edu

0002-9378/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.ajog.2004.09.021
 RETURN TO TABLE OF CONTENTS
Hendler et al
Table I Characteristics and pregnancy outcome in obese and nonobese women
Patients characteristic Obese (n = 597)
BMI (kg/m2)* 36.2 G 5.3
Maternal age (y)* 25.7 G 5.6
Gravidity (n)* 3.0 G 1.8
Nulliparity (%) 33
Education (y)* 12.1 G 1.7
Married (%) 33
Previous SPB (%) 10
Black race (%) 65
Smoking (%) 29
Family income !$800/mo (%) 64
Gestation at delivery (wk)* 38.6 G 2.5
Cesarean delivery (%) 29
Birth weight (g)* 3287 G 660
Birth weight O4000 g (%) 10
* Data are given as mean G SD.
Obesity is defined by the National Institutes of
Health as a body mass index (BMI) of R30 kg/m2.1
The prevalence of obesity among adults in the United
States has increased from 12% in 1991 to 20.9% in
2001.2 Obesity in nonpregnant women is a known risk
factor for many disorders, including diabetes mellitus,
atherosclerosis, and certain malignancies, and it is the
second leading cause of preventable death in the United
States.3,4 Previous studies have reported the association
between maternal obesity and many adverse pregnancy
outcomes, which include fetal anomalies, miscarriages,
preeclampsia, gestational diabetes mellitus, cesarean
deliveries, shoulder dystocia, and intrauterine fetal
demise.5-14 However, evidence regarding the association
of maternal obesity and spontaneous preterm birth
(SPB) is conflicting. Although some studies suggest that
obesity does not influence the rate of preterm birth at
!37 weeks of gestation,6-8,13 other studies have found
reduced rates of preterm birth in obese and morbidly
obese patients.9,11,12,14 Finally, other studies have re-
ported increased preterm birth in obese gravidas.10 Of
note, in these retrospective studies, the main objective
was to assess the adverse effects of obesity on pregnancy;
preterm birth was one of many variables that were
studied; the type of preterm birth (ie, after spontaneous
preterm labor, preterm premature rupture of mem-
branes, or indicated labor) was not distinguished, and
confounding variables that were associated with preterm
birth were not addressed.
At the other end of the spectrum, low maternal
weight has been associated repeatedly with an increased
risk of SPB.15-20 In a previous analysis from the Preterm
Prediction Study of the Maternal-Fetal Medicine Units
Network, we evaluated clinical risk factors for preterm
birth and found a significantly increased risk of SPB
with maternal BMI at !19.8 kg/m2.19 The purpose of
this analysis was to further evaluate the relationship
883
Nonobese (n = 2313) P value
22.7 G 3.5 ! .0001
23.3 G 5.4 ! .0001
2.6 G 1.6 ! .0001
44 ! .0001
11.8 G 2.0 ! .0001
27 .005
13 .019
62 .15
31 .31
61 .15
38.3 G 2.6 .005
15 ! .0001
3114 G 633 ! .0001
5 ! .0001
between maternal BMI and the rate of spontaneous and
indicated preterm birth, after controlling for potentially
confounding factors, in a prospectively evaluated cohort
of women.
Material and methods
This was a secondary analysis of the prospective
observational Preterm Prediction Study performed by
the Maternal-Fetal Medicine Units Network of the
National Institute of Child Health and Human De-
velopment. The primary study was conducted in 10
medical centers from 1992 to 1994. The overall study
population and methods for this study has been de-
scribed previously and will be briefly reviewed.21 In-
stitutional Review Board approval was obtained at each
of the 10 centers that participated in the original
investigation. Each study participant provided informed
consent. Exclusion criteria included multifetal gestation,
prenatally detected major fetal anomalies, a history of
cervical cerclage in the current pregnancy and placenta
previa. Gestational age was based on the last menstrual
period, if the last menstrual period and the earliest
ultrasound evaluation agreed within 10 days. If not, the
earliest ultrasound evaluation was used to define gesta-
tional age. The initial study visit occurred at 23 to 24
weeks of gestation, with 3 additional visits scheduled at
2-week intervals until 31 weeks of gestation. Extensive
demographic and outcome data were collected. Samples
of maternal serum and cervical fluid, which included
Gram stain for diagnosis of bacterial vaginosis, were
collected at the initial (23-24 weeks of gestation) and the
third visit (27-28 weeks of gestation).
We performed a secondary analysis on all patients for
whom maternal height and pre-pregnancy weight were
available. Prepregnancy maternal BMI was calculated
 RETURN TO TABLE OF CONTENTS
884
Figure 1 The percent of spontaneous preterm birth (SPB) at
!37, at !34, and at !32 weeks of gestation in nonobese and
obese patients.
for each patient (weight in kilograms/height in meters2).
For some of the analyses, patients were classified as non-
obese (BMI, !30 kg/m2) or obese (BMI, R30 kg/m2),
for other analyses, women were classified into groups
according to the National Institutes of Health guide-
lines,1 underweight (BMI, !19 kg/m2), normal weight
(BMI, 19-24.9 kg/m2), overweight (BMI, 25-29.9 kg/m2),
class I obesity (BMI, 30-34.9 kg/m2), and class II or
morbid obesity (BMI, R35 kg/m2). Our primary out-
come was SPB because of premature rupture of mem-
branes or spontaneous labor before 37 weeks of
gestation. Other outcomes included SPB at !34 and
!32 weeks and the rate of indicated preterm birth.
Statistical analyses were performed with the SAS
software (version 8.2; SAS Institute Inc, Cary, NC).
Categoric variables were compared with the use of
the chi-squared and Fisher’s exact tests. The Mantel-
Haenszel chi-squared test was used to test for trends
across BMI categories. Multivariable logistic regression
was used to assess the relationship between SPB and
maternal BMI, while being controlled for potential
confounders (age, race, previous SPB, bacterial vagi-
nosis, fetal fibronectin, and cervical length [CL]).
Results
A total of 2910 of the originally enrolled 2929 patients
met eligibility requirements and were included in this
analysis. There were 597 obese women (BMI, R30 kg/m2;
20.5%). Obese women were older than nonobese
women, were more likely to be multiparous, had more
years of education, were married more often, and were
less likely to have had a previous spontaneous preterm
delivery (10% vs 13%; P = .019) than nonobese women
(Table I). However, there were no differences in the rate
of smoking, race, or family income between groups.
Obese women had larger infants (3287 G 660 g vs.
3114 G 633 g; P ! .0001), delivered at a more advanced
Hendler et al
Figure 2 The percent of spontaneous (SPB) and indicated
preterm births (PTB) at !37 weeks of gestation in various
BMI groups.
gestational age (38.6 G 2.5 weeks vs 38.3 G 2.6 weeks;
P = .005), and had more frequent cesarean deliveries
(29% vs 15%; P ! .0001). Obese patients had signifi-
cantly lower rates of SPB at !37 weeks of gestation
(6.2% vs 11.2%; P = .0003), and at !34 weeks of
gestation (1.5% vs 3.5%; P = .012; Figure 1). The odds
ratio (OR; 95% CI) of an obese patient to have a SPB
was approximately one-half that for a nonobese patient
(!37 weeks of gestation: OR, 0.5; 95% CI, 0.4-0.7; !34
weeks of gestation: OR, 0.4; 95% CI, 0.2-0.8; !32
weeks of gestation: OR, 0.5, 95% CI, 0.2-1.3).
When the patients’ BMIs were classified into groups
according to the National Institutes of Health guide-
lines,1 the risk of SPB at !37 weeks of gestation
progressively decreased with increasing BMI: under-
weight, 16.6%; normal weight, 11.3%; overweight,
8.1%; class I obesity, 7.1%; class II or morbid obesity,
5.2%; P ! .0001; Figure 2).
The total rate of preterm deliveries, which included
both spontaneous and indicated deliveries, was also
lower in obese women (11.1% vs 15.3%; P = .009). The
frequency of indicated preterm birth was comparable in
obese and nonobese patients (4.9% vs 4.0%), but
indicated preterm birth accounted for a higher percent-
age of preterm birth in the obese than nonobese patient
(44% vs 24%; P = .003). Figure 2 shows the relative
proportions of indicated preterm birth and SPB for each
BMI group. In obese patients, 18 of 29 indicated
preterm deliveries (62%) were due to maternal pre-
eclampsia, compared with 33 of 92 indicated preterm
deliveries (36%) for the nonobese women (P = .013).
Among women who were delivered at !37 weeks of
gestation, we found indicated preterm birth to be
responsible for an increasing proportion of preterm
births with increasing maternal BMI (P = .001).
Obese women had a longer CL compared with
nonobese women, (36.5 G 8.4 mm vs 34.9 G 8.1 mm;
 RETURN TO TABLE OF CONTENTS
Hendler et al
P ! .0001; Table II). Obese women had lower rates of
CL ! 30 mm (16% vs 21%; P = .02) and CL !25 mm
(5% vs 8%; P = .012). However, fetal fibronectin
positivity and bacterial vaginosis were comparable
among obese and nonobese gravidas.
Multivariable logistic regression analysis was per-
formed to adjust for confounding variables that are
known to be associated with SPB: maternal age, parity,
education, history of SPB, black race, bacterial vagi-
nosis, fetal fibronectin positivity, and CL at 23 to 24
weeks of gestation. Obesity was associated significantly
with decreased SPB at !37 weeks of gestation (OR,
0.57; 95% CI, 0.39-0.83; P = .003). The results were
similar, but not significant, for SPB at !34 weeks of
gestation (OR, 0.58; 95% CI, 0.28-1.21; P = .15). When
BMI was included in the model as a continuous vari-
able, the adjusted odds ratio for SPB at !37 weeks of
gestation declined by 21% for each 5-unit increase in
maternal BMI (P ! .0001).
Comment
BMI, which is derived from the weight and height
measurements, is one of the best markers of nutritional
status and is used to classify populations from thin to
obese. In this study, we evaluated the entire range of
prepregnancy BMIs and compared them to the rates of
indicated preterm births and SPBs. We found that
prepregnancy obesity, defined as BMI R30 kg/m2, was
associated with fewer total preterm births and fewer
SPBs. Maternal thinness on the other hand was associ-
ated with increased preterm birth and especially SPBs. A
significantly high percentage of the preterm births of
obese women were indicated, often in association with
preeclampsia, compared with the preterm births of thin
women. An additional finding is that obese women
tended to have longer CLs than nonobese women.
In agreement with our results, Gross et al11 found
that obese patients (body weight O90 kg) had a 9.9%
rate of preterm birth at !38 weeks of gestation com-
pared with 19.9% for nonobese patients. Kumari12 ana-
lyzed 488 morbidly obese patients (BMI, R40 kg/m2)
and found an OR of 0.1 (95% CI, 0.01-0.7) for preterm
birth at !37 weeks of gestation. Sebire et al9 found that
obese gravidas (n = 287,213) had a reduced risk for
preterm birth at !32 weeks of gestation (OR, 0.81; 95%
CI, 0.69-0.95) but not at !37 weeks of gestation;
Cnattingius et al10 found an increased risk for SPB
(n = 167,750) at %32 weeks of gestation in obese
nulliparous patients (OR, 1.6; 95% CI, 1.1-1.3). Alter-
natively, Cedergren13 found an increased risk for PTB
(n = 805,275) at !37 and !32 weeks of gestation
(4.5% and 0.6% for BMI !29 kg/m2, compared with
5.4% and 0.8% for BMI 29.0-35 kg/m2).
The disparity in results between different studies may
be due to the use of population registries, to different
885
Table II Tests predictive of SPB at 24 weeks of gestation in
obese and nonobese women
Clinical characteristic Obese Nonobese P
(visit 1) (n = 595) (n = 2301) value
CL (mm)* 36.5 G 8.4 34.9 G 8.1 ! .0001
CL !30 mm (%) 16.5 21.0 .015
CL !25 mm (%) 5.2 8.3 .012
CL !20 mm (%) 2.7 3.2 .51
Fetal fibronectin 3.4 4.2 .37
positive (%)
Bacterial vaginosis 23.5 23.1 .84
positive (%)
* Data are given as mean G SD.
definitions of spontaneous and indicated preterm birth,
or to the different populations that are studied. Our
analysis has the benefit of being based on prospectively
collected data in a study that was aimed to determine
risk factors for SPB, and the results are corrected for
confounding variables that are associated with SPB.
Many studies have found an association between low
maternal weight and an increased risk of SPB.15-20
Ehrenberg et al15 recently described a population of
15,196 patients in which low BMI (!19.8 kg/m2) at
conception and low BMI at the time of birth were
associated with an increased risk for SPB. Using
a multivariable analysis in a population of 17,000
patients, Wen et al20 showed that a previous preterm
delivery and very low maternal weight had the greatest
association with preterm birth. Thus, because low
maternal weight is associated with an increased rate of
SPB, there may be a continuous inverse association
between BMI and the risk for SPB.
Obese women had lower rates of CL of !30 mm
(17% vs 21%; P = .02) and CL of !25 mm (5% vs 8%;
P = .012). Similar results were found in Thai women, in
whom the cervix was significantly longer in women with
a BMI of O26 kg/m2.22 The longer CL may explain part
of the reduced rate of SPB that is seen in obese women.
Preterm births that occur !30 weeks of gestation are
more often associated with intra-amniotic inflammation
and infection.23,24 Maternal obesity is known to be
associated with an increased production of systemic
proinflammatory cytokines.25 Thus, the reduced rate of
spontaneous preterm labor in the obese population is
not likely due to a reduced systemic inflammatory
process, but whether an actual infectious process is
involved is unknown. Some studies describe malnutri-
tion as a factor in the cause of SPB. Decreased intake of
calories, proteins, vitamins, and minerals, which often
are associated with decreased BMI, may explain the
higher rate of SPB in thin patients.16 In obese women,
the increased intake of various nutrients may be related
to a reduced rate of SPB. However, by an unknown
mechanism, obesity is associated with an increased risk
 RETURN TO TABLE OF CONTENTS
886
of preeclampsia; thus, the rate of indicated preterm
births is increased in obese women.
In summary, we found a strong inverse association
between prepregnancy BMI and SPB at !37 weeks of
gestation. Further research is needed to investigate the
different mechanisms that are responsible for spontaneous
and indicated preterm birth in obese and nonobese women.
Acknowledgments
Participating institutions and staff members: University
of Alabama, Birmingham: J.C. Hauth, A. Northen, R.
Copper, C. Neely; Bowman Gray School of Medicine:
E. Mueller-Heubach, M. Swain, A. Frye; University of
Chicago: M. Lindheimer, P. Jones, M.E. Lewis-Brown;
University of Cincinnati: T.A. Siddiqi, N. Elder, T.
Coombs, J. VanHorn; George Washington University
Biostatistics Center: E. Thom, R. Bain, A. Das, L.
Leuchtenburg, M. Fischer; University of Pittsburgh
Magee Women’s Hospital: J.H. Harger, M. Cotroneo,
C. Stallings; National Institutes of Child Health and
Human Development: D. McNellis, S. Yaffe, C. Catz,
M. Klebanoff; Ohio State University: M.B. Landon, F.
Johnson, J. Schneider, C. Mueller; University of Okla-
homa, Oklahoma City: J.C. Carey, A. Meier, E. Liles;
Medical University of South Carolina: R.B. Newman,
B.A. Collins, J.T. VanDorsten, F. LeBoeuf; Odell;
University of Tennessee, Memphis: B. Sibai, R. Ramsey,
J.L. Fricke; Wayne State University: S. Bottoms (de-
ceased), M.P. Dombrowski, M. Treadwell, G.S. Nor-
man; and University of Pittsburgh: J.M. Roberts,
Steering Committee Chair.
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2. Vastag B. Obesity is now on everyone’s plate. JAMA 2004;
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3. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F,
Bales VS, et al. Prevalence of obesity, diabetes, and obesity-
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at its high toll. JAMA 2003;289:229-30.
5. Watkins ML, Rasmussen SA, Honein MA, Botto LD, Moore CA.
Maternal obesity and risk for birth defects. Pediatrics 2003;
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6. Jensen DM, Damm P, Sorensen B, Molsted-Pederson L, West-
ergaard JG, Oveson P, et al. Pregnancy outcome and prepregnancy
body mass index in 2459 glucose-tolerant Danish women. Am J
Obstet Gynecol 2003;189:239-44.
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7. Rosenberg TJ, Garbers S, Chavkin W, Chiasson MA. Prepreg-
nancy weight and adverse perinatal outcomes in an ethnically
diverse population. Obstet Gynecol 2003;102:1022-7.
8. Castro LC, Avina RL. Maternal obesity and pregnancy outcomes.
Curr Opin Obstet Gynecol 2002;14:601-6.
9. Sebire NJ, Jolly M, Harris JP, Wadsworth J, Jaffe M, Beard RW,
et al. Maternal obesity and pregnancy outcome: a study of
287,213 pregnancies in London. Int J Obes Relat Metab Disord
2001;25:1175-82.
10. Cnattingius S, Bergstrom R, Lipworth L, Kramer MS. Prepreg-
nancy weight and the risk of adverse pregnancy outcomes. N Engl
J Med 1998;338:147-52.
11. Gross T, Sokol RJ, King KC. Obesity in pregnancy: risks and
outcome. Obstet Gynecol 1980;56:446-50.
12. Kumari AS. Pregnancy outcome in women with morbid obesity.
Int J Gynaecol Obstet 2001;73:101-7.
13. Cedergren MI. Maternal morbid obesity and the risk of adverse
pregnancy outcome. Obstet Gynecol 2004;103:219-24.
14. Schieve LA, Cogswell ME, Scanlon KS, Perry G, Ferre C,
Blackmore-Prince C, et al. Prepregnancy body mass index and
pregnancy weight gain: associations with preterm delivery: the
NMIHS Collaborative Study Group. Obstet Gynecol 2000;
96:194-200.
15. Ehrenberg HM, Dierker L, Milluzzi C, Mercer BM. Low maternal
weight, failure to thrive in pregnancy, and adverse pregnancy
outcomes. Am J Obstet Gynecol 2003;189:1726-30.
16. Neggers Y, Goldenberg RL. Some thoughts on body mass index,
micronutrient intakes and pregnancy outcome. J Nutr 2003;
133:1737S-40S.
17. Hickey CA, Cliver SP, McNeal SF, Goldenberg RL. Low
pregravid body mass index as a risk factor for preterm birth:
variation by ethnic group. Obstet Gynecol 1997;89:206-12.
18. Hickey CA, Cliver SP, McNeal SF, Hoffman HJ, Goldenberg RL.
Prenatal weight gain patterns and spontaneous preterm birth
among non-obese black and white women. Obstet Gynecol
1995;85:909-14.
19. Mercer BM, Goldenberg RL, Das A, Moawad AH, Iams JD, Meis
PJ, et al. The preterm prediction study: a clinical risk assessment
system. Am J Obstet Gynecol 1996;174:1885-95.
20. Wen SW, Goldenberg RL, Cutter GR, Hoffman HJ, Cliver SP.
Intrauterine growth retardation and preterm delivery: prenatal risk
factors in an indigent population. Am J Obstet Gynecol 1990;
162:213-8.
21. Goldenberg RL, Iams JD, Mercer BM, Meis PJ, Moawad AH,
Copper RL, et al. The preterm prediction study: the value of new
vs standard risk factors in predicting early and all spontaneous
preterm births: NICHD MFMU Network. Am J Public Health
1998;88:233-8.
22. Liabsuetrakul T, Suntharasaj T, Suwanrath C, Leetanaporn R,
Rattanaprueksachart R, Tuntiseranee P. Serial translabial sono-
graphic measurement of cervical dimensions between 24 and 34
weeks’ gestation in pregnant Thai women. Ultrasound Obstet
Gynecol 2002;20:168-73.
23. Iams JD. Prediction and early detection of preterm labor. Obstet
Gynecol 2003;101:402-12.
24. Romero R, Ghezzi F, Yoon BH, Mazor M, Edwin SS, Berry SM.
A fetal systemic inflammatory response is followed by the
spontaneous onset of preterm parturition. Am J Obstet Gynecol
1998;179:186-93.
25. Ramsay JE, Crawford L, Wallace AM, Greer IA, Sattar N.
Maternal obesity is associated with dysregulation of metabolic,
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2002;87:4231-7.
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Papers
Interpregnancy interval and risk of preterm birth and
neonatal death: retrospective cohort study
Gordon C S Smith, Jill P Pell, Richard Dobbie
Abstract
Objective To determine whether a short interval
between pregnancies is an independent risk factor for
adverse obstetric outcome.
Design Retrospective cohort study.
Setting Scotland.
Subjects 89 143 women having second births in
1992-8 who conceived within five years of their first
birth.
Main outcome measures Intrauterine growth
restriction (birth weight less than the 5th centile for
gestational age), extremely preterm birth (24-32
weeks), moderately preterm birth (33-36 weeks), and
perinatal death.
Results Women whose subsequent interpregnancy
interval was less than six months were more likely
than other women to have had a first birth
complicated by intrauterine growth restriction (odds
ratio 1.3, 95% confidence interval 1.1 to 1.5),
extremely preterm birth (4.1, 3.2 to 5.3), moderately
preterm birth (1.5, 1.3 to 1.7), or perinatal death (24.4,
18.9 to 31.5). They were also shorter, less likely to be
married, and more likely to be aged less than 20 years
at the time of the second birth, to smoke, and to live
in an area of high socioeconomic deprivation. When
the outcome of the second birth was analysed in
relation to the preceding interpregnancy interval and
the analysis confined to women whose first birth was
a term live birth (n = 69 055), no significant
association occurred (adjusted for age, marital status,
height, socioeconomic deprivation, smoking, previous
birth weight vigesimal, and previous caesarean
delivery) between interpregnancy interval and
intrauterine growth restriction or stillbirth. However, a
short interpregnancy interval ( < 6 months) was an
independent risk factor for extremely preterm birth
(adjusted odds ratio 2.2, 1.3 to 3.6), moderately
preterm birth (1.6, 1.3 to 2.0), and neonatal death
unrelated to congenital abnormality (3.6, 1.2 to 10.7).
The adjusted attributable fractions for these
associations were 6.1%, 3.9%, and 13.8%. The
associations were very similar when the analysis was
confined to married non-smokers aged 25 and above.
Conclusions A short interpregnancy interval is an
independent risk factor for preterm delivery and
neonatal death in the second birth.
BMJ VOLUME 327 9 AUGUST 2003 bmj.com
Introduction Department of
Obstetrics and
Several studies have shown that women with a very Gynaecology,
Cambridge
short interval between pregnancies are at increased University, Box 223,
risk of complications such as preterm birth, neonatal The Rosie Hospital,
Cambridge
death, and intrauterine growth restriction.1–10 However, CB2 2QQ
these studies do not clarify whether the associations Gordon C S Smith
are due to confounding effects of adverse obstetric his- professor
tory or to demographic factors. Women with very short Department of
interpregnancy intervals are more likely to have had Public Health,
Greater Glasgow
complications such as perinatal death, preterm birth,
NHS Board,
and intrauterine growth restriction in their first Glasgow
pregnancy.11 A short interpregnancy interval is also Jill P Pell
consultant
associated with known demographic risk factors for
complications of pregnancy.12 13 Many previous studies Information and
Statistics Division,
of the association between interpregnancy interval and Common Services
the risk of adverse outcome have lacked information Agency, Edinburgh
on maternal demographic factors and have had either Richard Dobbie
no information on the outcome of previous pregnan- senior statistician
cies or minimal information. None of the studies that Correspondence to:
G C S Smith
were powered to detect differences in rare but gcss2@cam.ac.uk
important outcomes, such as perinatal death and
extremely preterm birth, had data on key obstetric and bmj.com 2003;327:313
demographic confounders.6 7 9 10 We report the relation
between interpregnancy interval and the outcome of
first and second births in a cohort of 89 143 women.
Methods
Data sources
The Scottish Morbidity Record collects information on
clinical and demographic characteristics and outcomes
for all patients discharged from Scottish maternity
hospitals. The register is subjected to regular quality
assurance checks and has been greater than 99% com-
plete since the late 1970s.14 We linked records from the
register to records from the Scottish Stillbirth and
Infant Death Enquiry, a national register that routinely
classifies all perinatal deaths in Scotland. It is virtually
100% complete and has been described in detail
elsewhere.15 16 We also linked the records from different
pregnancies in the same women. All linkages were per-
formed as previously described.17
Study cohort
The population studied consisted of all second births
in Scotland in 1992-8. The study focused on births in
1992-8 as the Scottish Morbidity Record database
included smoking status only from 1992 onwards.
When studying the relation between interpregnancy
page 1 of 6
 RETURN TO TABLE OF CONTENTS
Papers
interval and the outcome of the first pregnancy, we
used exclusion criteria (both pregnancies) of multiple
pregnancy, delivery outside the range 24-43 weeks’
gestation, and birth weight less than 500 g. We also
excluded cases in which the interpregnancy interval
was negative or implausibly short, a discrepancy
existed between the documented mode of delivery in
the first record and the previous caesarean delivery
field in the second record, or the number of previous
spontaneous or therapeutic abortions differed
between the first and second birth record. The last of
these processes excluded cases in which the records
were discrepant (fewer losses documented for the
second birth) and cases in which the woman had expe-
rienced losses between the two births (more losses
documented for the second birth). These inclusions
and exclusions identified the first study group.
We analysed the relation of interpregnancy interval
to the outcome of the second birth in a subgroup of
the main cohort. We defined this subgroup by exclud-
ing cases in which the first birth was outside the range
37-43 weeks, the first birth was a perinatal or infant
death, or the birth weight of the first child was less than
1500 g. We also excluded cases in which data were
missing on potential confounders in the second preg-
nancy record: maternal age, marital status, height, dep-
rivation category, or smoking status. We also excluded
cases in which the birth weight vigesimal of the first
pregnancy was missing. These inclusions and exclu-
sions identified the second study group.
Definitions
Maternal characteristics
In the comparison of risk of adverse obstetric outcome,
we considered the following demographic factors as
possible confounders: socioeconomic deprivation,
smoking, maternal age, and maternal height; their
classification has been defined elsewhere.18 We also
included marital status, defined as the status docu-
mented at the time of booking for antenatal care and
categorised into married and non-married.
Obstetric characteristics
We defined first births as either first pregnancies or
births preceded only by pregnancies that resulted in
abortion. We defined second births as having been
preceded by one pregnancy that did not result in abor-
tion. We defined gestational age at birth as the number
of completed weeks of gestation based on the
estimated delivery date contained in the clinical record.
Over the study period the vast majority of estimates of
gestational age in the United Kingdom incorporated
ultrasound measurements taken in the first half of
pregnancy.19 We defined interpregnancy interval as the
interval from the first birth until the estimated date of
the last menstrual period before the second pregnancy,
expressed in completed months. We calculated the
ultrasound corrected date of the last menstrual period
by subtracting the gestational age at birth from the date
of delivery. In order to avoid bias in categorisation of
interpregnancy interval, we used the categories used by
a previous large scale study.7
We categorised birth weight into sex specific and
gestational age specific vigesimals (20 equal groups)
derived from live births among the whole population.
page 2 of 6
We defined a small for gestational age baby as a liveborn
baby with a birth weight in the smallest vigesimal (that is,
0 to 5th centile), and the denominator was all live births.
We defined very preterm delivery as live births between
24 and 32 weeks’ gestation inclusive, and the denomina-
tor was all live births at or after 24 weeks’ gestation. We
defined moderately preterm delivery as live births
between 33 and 36 weeks’ gestation inclusive, with a
denominator of all live births at or after 33 weeks’ gesta-
tion. We defined spontaneous preterm birth as vaginal
birth at the given gestational age, excluding cases in
which labour was induced. We defined stillbirth as deliv-
ery of a dead baby at or after 24 weeks’ gestational age,
and the denominator was all births at or after 24 weeks’
gestational age. We defined neonatal death as death of a
liveborn infant in the first four weeks of life, and the
denominator was all live births.
Perinatal deaths
We defined deaths caused by congenital anomaly as
any structural or genetic defect incompatible with life
or potentially treatable but causing death. We classified
stillbirths as antepartum (deaths before the onset of
labour) or intrapartum (deaths during labour). We
classified the cause of antepartum stillbirth according
to a modified version of the Wigglesworth hierarchical
system,20 which is described in detail elsewhere.16 We
classified perinatal deaths into four mutually exclusive
categories: (a) all deaths related to fetal abnormality or
rhesus isoimmunisation; (b) unexplained stillbirths; (c)
all other stillbirths; and (d) all other neonatal deaths
(excluding category (a)).
Statistical analyses
We summarised continuous variables by the median
and interquartile range and used the Mann-Whitney U
test to make comparisons between groups. We made
univariate comparisons of dichotomous data by using
the
2 test ( > 5 observations in all cells) or Fisher’s
exact test ( ≤ 5 observations in one or more cells). The
P values for all hypothesis tests were two sided, and we
set statistical significance at P < 0.05. We used
multivariate logistic regression analysis to assess the
risk of adverse obstetric outcome. We did both univari-
ate and multivariate analyses on only those records
with no missing values for any of the maternal covari-
ates included in the multivariate model. We used the
Hosmer and Lemeshow test to assess the goodness of
fit of logistic regression models.21 We assessed the
statistical significance of interaction terms by using the
likelihood ratio test and assumed significance of inter-
actions at P < 0.01. We defined the attributable fraction
as Pr(exposed/disease)*(1 − 1/relative risk). This can
be conceptualised as the proportion of cases that
would have been prevented if the exposure did not
exist in a population. We calculated adjusted attribut-
able fractions after multivariate logistic regression by
using the method of Greenland and Drescher.22 We
used the Stata software package, version 7.0, for all
statistical analyses.
Results
The figure outlines the selection of the two study
groups. Approximately 5.4% of the cohort had an
interpregnancy interval of less than six months.
BMJ VOLUME 327 9 AUGUST 2003 bmj.com
 RETURN TO TABLE OF CONTENTS

Papers

Women who subsequently had a short interpregnancy

interval were more likely to have experienced compli- Second births, 1992-8 (n=144 457)
cations in their first pregnancy (table 1). Compared
with women who had an interpregnancy interval of Data on birth weight and gestation available
Data missing or ineligible (n=414)
18-23 months, those with an interval of less than six for second pregnancy (n=144 043)
months had a 30-50% excess of intrauterine growth
restriction and moderately preterm birth in their first Record for first pregnancy in 1980-98, interpregnancy No record or outside
pregnancy, a fourfold excess of extremely preterm range 29-1826 days (inclusive) (n=107 414) range (n=36 629)

birth, and a greater than 20-fold excess of perinatal

deaths. An excess of extremely preterm first births
existed among women whose subsequent interpreg-
nancy interval was 2-5 years.
All analyses of the outcome of the second birth
were confined to the subgroup of women whose first
birth was a term live birth. Even among this group, at
the time of their second delivery, women with a short
interval between their first and second pregnancy were
more likely to be aged less than 20, to smoke, and to
live in an area of high deprivation and were less likely
to be married, to be aged greater than 35, and to live in
an area of low socioeconomic deprivation (table 2).
On univariate analysis of obstetric outcome in the
second birth, women with a short interpregnancy inter-
val were more likely to have an extremely preterm birth,
a moderately preterm birth, or a neonatal death (table
3). The strength of these associations was attenuated by
adjustment for maternal age, marital status, height,
socioeconomic deprivation category, smoking, previous
birth weight vigesimal, and previous caesarean section,
but significant associations persisted in multivariate
analysis. The adjusted attributable fractions for these
associations were 6.1% (95% confidence interval 1.9% to
10.2%) for extremely preterm birth, 3.9% (1.3% to 4.2%)
for moderately preterm birth, and 13.8% (0.2% to
25.6%) for neonatal death unrelated to fetal abnormality.
The excess of preterm second births persisted when the
analysis was confined to spontaneous preterm births. An
interpregnancy interval of less than six months was
associated with an increased risk (compared with an
interpregnancy interval of 18-23 months) of spontane-
ous preterm birth, both 24-32 weeks (adjusted odds ratio
2.2, 95% confidence interval 1.2 to 4.1) and 33-36 weeks
(1.6, 1.2 to 2.2). The associations between interpreg-
nancy interval and unexplained stillbirth were virtually
identical when estimated using time to event methods
(data not shown).
Data on birth weight and gestation available for first
Data missing or records
pregnancy and no discrepancy between mode of delivery in
first record and previous caesarean field in second (n=105 270)
discrepant (n=2144)
Number of therapeutic or spontaneous abortions
identical in first and second records
Number differs (n=16 127)
Study group 1 (n=89 143)
First pregnancy outside range,
First pregnancy within range 37-43 weeks, birth weight
>1500 g, and did not end in perinatal death (n=83 290)
birth weight <1500 g, or ended
in perinatal death (n=5853)
No missing values in second pregnancy record
for maternal height, deprivation category, Missing values (n=14 235)
age, smoking status, or marital status
Study group 2 (n=69 055)
Flow diagram of cohort selection
We explored the relations between interpregnancy
interval, maternal age, and other maternal factors and
the outcome of the second birth in more detail. The
attenuation of the association between interpregnancy
interval and adverse outcome in multivariate analysis
was principally due to the effect of adjustment for age
(table 4). The odds ratio for interpregnancy interval
adjusted for age alone was very similar to the odds
ratio adjusted for age plus the other maternal
covariates. Maternal age less than 20 years at the time
of the second birth was strongly associated with
preterm birth and neonatal death. The association
remained statistically significant in multivariate analy-
sis but was attenuated by adjustment for both
interpregnancy interval and other maternal factors. No
statistically significant interactions existed between
interpregnancy interval and maternal age, marital

Table 1 Outcome of first pregnancy in relation to interval between first and second pregnancies (n=89 143)
Interpregnancy interval*
18-23
1-5 months 6-11 months 12-17 months months* 24-59 months
Odds ratio Odds ratio Odds ratio Odds ratio
Outcome of first pregnancy No (%) (95% CI) No (%) (95% CI) No (%) (95% CI) No (%) No (%) (95% CI)
No of births 4816 – 11 927 – 15 771 – 15 014 41 615 –
Birth weight <5th centile 298 (6.6) 1.3 (1.1 to 1.5) 613 (5.2) 1.0 (0.9 to 1.1) 804 (5.1) 1.0 (0.9 to 1.1) 768 (5.1) 2347 (5.6) 1.1 (1.0 to 1.2)
Preterm delivery:
24-32 weeks 146 (3.2) 4.1 (3.2 to 5.3) 181 (1.5) 1.9 (1.5 to 2.4) 155 (1.0) 1.2 (1.0 to 1.6) 120 (0.8) 458 (1.1) 1.4 (1.1 to 1.7)
33-36 weeks 257 (5.9) 1.5 (1.3 to 1.7) 570 (4.9) 1.2 (1.1 to 1.4) 662 (4.3) 1.1 (1.0 to 1.2) 592 (4.0) 1830 (4.4) 1.1 (1.0 to 1.2)
Perinatal death:
All causes† 481 (10.0) 24.4 (18.9 to 31.5) 247 (2.0) 4.6 (3.5 to 6.1) 103 (0.6) 1.4 (1.1 to 2.0) 68 (0.4) 120 (0.3) 0.6 (0.5 to 0.9)
Fetal abnormality or rhesus 71 (1.5) 15.0 (8.6 to 26.1) 38 (0.3) 3.2 (1.8 to 5.8) 21 (0.1) 1.3 (0.7 to 2.6) 15 (0.1) 26 (0.1) 0.6 (0.3 to 1.2)
Unexplained stillbirth 188 (3.9) 30.5 (19.2 to 48.3) 87 (0.7) 5.5 (3.4 to 9.0) 37 (0.2) 1.8 (1.0 to 3.0) 20 (0.1) 36 (0.1) 0.6 (0.4 to 1.1)
All other stillbirths 109 (2.3) 20.4 (12.2 to 34.1) 55 (0.5) 4.1 (2.4 to 7.0) 21 (0.1) 1.2 (0.6 to 2.2) 17 (0.1) 24 (0.1) 0.5 (0.3 to 0.9)
All other neonatal deaths 110 (2.3) 23.4 (13.6 to 40.1) 65 (0.5) 5.5 (3.1 to 9.6) 23 (0.2) 1.5 (0.8 to 2.8) 15 (0.1) 34 (0.1) 0.8 (0.4 to 1.5)
All percentages calculated relative to appropriate denominators (see methods).
*Reference category for odds ratios was women with interpregnancy interval of 18-23 months.
†Seven perinatal deaths were not classified.

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Table 2 Demographic factors at time of second pregnancy in relation to interpregnancy interval in women with previous term live
birth (n=69 055). Values are numbers (percentages)
Interpregnancy interval (months)
1-5 (n=3282) 6-11 (n=8999) 12-17 (n=12 220) 18-23 (n=11 793) 24-59 (n=32 761) Total (n=69 055) P value
Height (cm):
<155 349 (10.6) 843 (9.3) 1 068 (8.7) 1 125 (9.5) 3 614 (11.0) 6 990 (10.1)
155-170 2654 (80.9) 7160 (79.6) 9 868 (80.8) 9 398 (79.7) 26 299 (80.3) 55 379 (80.2) <0.001
>170 279 (8.5) 1005 (11.2) 1 284 (10.5) 1 270 (10.8) 2 848 (8.7) 6 686 (9.7)
Age (years):
<20 547 (16.7) 669 (7.4) 501 (4.1) 278 (2.4) 234 (0.7) 2 229 (3.2)
20-35 2624 (80.0) 7899 (87.8) 11 120 (91.0) 10 961 (92.9) 30 655 (93.6) 63 259 (91.6) <0.001
>35 111 (3.4) 431 (4.8) 599 (4.9) 554 (4.7) 1 872 (5.7) 3 567 (5.2)
Marital status:
Married 1949 (59.4) 6714 (74.6) 9 681 (79.2) 9 615 (81.5) 25 315 (77.3) 53 274 (77.2)
<0.001
Other 1333 (40.6) 2285 (25.4) 2 539 (20.8) 2 178 (18.5) 7 446 (22.7) 15 781 (22.8)
Deprivation category:
1 (least deprived) 484 (14.8) 1919 (21.3) 2 933 (24.0) 2 720 (23.1) 6 045 (18.4) 14 101 (20.4)
2-4 1915 (58.4) 5397 (60.0) 7 242 (59.3) 7 104 (60.2) 19 809 (60.5) 41 467 (60.0) <0.001
5 (most deprived) 883 (26.9) 1683 (18.7) 2 045 (16.7) 1 969 (16.7) 6 907 (21.1) 13 487 (19.5)
Smoking status:
Non-smoker 1839 (56.0) 6078 (67.5) 8 560 (70.0) 8 309 (70.5) 21 279 (65.0) 46 065 (66.7)
Ex-smoker 193 (5.9) 536 (6.0) 797 (6.5) 759 (6.4) 2 533 (7.7) 4 818 (7.0) <0.001
Smoker 1250 (38.1) 2385 (26.5) 2 863 (23.4) 2 725 (23.1) 8 949 (27.3) 18 172 (26.3)

status, height, socioeconomic deprivation category,
smoking, previous birth weight vigesimal, or previous
caesarean section in predicting adverse obstetric
outcome in the second pregnancy. The strengths of the
associations were virtually identical when confined to
married non-smokers aged 25 or above: in this group
an interpregnancy interval of less than six months was
associated with an odds ratios of 2.8 (1.3 to 5.9) for
extremely preterm birth and 1.7 (1.2 to 2.4) for moder-
ately preterm birth.
We considered the possibility that misclassification
of gestational age may have affected the results by
examining the association between interpregnancy
interval and absolute values of birth weight in the
second pregnancy. An interpregnancy interval of less
than six months was associated with an increased risk
of delivering a low birth weight neonate (adjusted odds
ratio 1.5, 1.2 to 1.8) or a very low birth weight neonate
(1.9, 1.0 to 3.4). We considered the possibility that
excluding the 14 255 cases with missing values for
potential confounders from the second study group
may have affected our results. However, univariate
analysis of second pregnancy outcomes including
these cases showed positive associations between a one
to five month interval (18-23 months as reference
group) and extreme preterm birth (odds ratio 2.8, 1.9
to 4.2), moderate preterm birth (2.0, 1.6 to 2.4), and
neonatal death unrelated to congenital abnormality
(3.2, 1.3 to 7.9).
Discussion
The main finding of this study is that in women having
a second birth a short preceding interpregnancy inter-

Table 3 Crude and adjusted odds ratios for interpregnancy interval and the outcome of the second pregnancy (n=69 055)
Interpregnancy interval*
18-23
months*
1-5 months (n=3282) 6-11 months (n=8999) 12-17 months (n=12 220) (n=11 793) 24-59 months (n=32 761)
Outcome of
second Odds ratio (95% CI) Odds ratio (95% CI) Odds ratio (95% CI) Odds ratio (95% CI)
pregnancy No (%) Crude Adjusted† No (%) Crude Adjusted† No (%) Crude Adjusted† No (%) No (%) Crude Adjusted†
Birth weight 99 1.1 0.8 234 1.0 0.9 325 1.0 1.0 321 987 1.1 1.0
<5th centile (3.0) (0.9 to 1.4) (0.7 to 1.1) (2.6) (0.8 to 1.1) (0.8 to 1.1) (2.7) (0.8 to 1.1) (0.8 to 1.2) (2.7) (3.0) (1.0 to 1.3) (0.9 to 1.1)
Preterm delivery:
24-32 32 3.1 2.2 46 1.6 1.4 48 1.2 1.2 38 122 1.2 1.1
weeks (1.0) (1.9 to 4.9) (1.4 to 3.6) (0.5) (1.0 to 2.4) (0.9 to 2.2) (0.4) (0.8 to 1.9) (0.8 to 1.8) (0.3) (0.4) (0.8 to 1.7) (0.8 to 1.6)
33-36 130 2.0 1.6 218 1.2 1.1 280 1.1 1.1 244 800 1.2 1.2
weeks (4.0) (1.6 to 2.4) (1.3 to 2.0) (2.4) (1.0 to 1.4) (0.9 to 1.3) (2.3) (0.9 to 1.3) (0.9 to 1.3) (2.1) (2.5) (1.0 to 1.4) (1.0 to 1.3)
Perinatal death:
Fetal 6 1.4 1.2 12 1.0 1.0 17 1.1 1.2 15 45 1.1 1.1
abnormality (0.2) (0.6 to 3.7) (0.5 to 3.3) (0.1) (0.5 to 2.2) (0.5 to 2.1) (0.1) (0.5 to 2.2) (0.5 to 2.2) (0.1) (0.1) (0.6 to 1.9) (0.6 to 2.0)
or rhesus
Unexplained 7 1.6 1.2 10 0.8 0.7 20 1.2 1.2 16 55 1.2 1.2
stillbirth (0.2) (0.6 to 3.8) (0.5 to 3.0) (0.1) (0.4 to 1.8) (0.3 to 1.7) (0.2) (0.6 to 2.3) (0.6 to 2.3) (0.1) (0.2) (0.7 to 2.2) (0.7 to 2.1)
All other 5 2.6 2.3 9 1.7 1.7 12 1.7 1.7 7 27 1.4 1.2
stillbirths (0.2) (0.8 to 8.1) (0.7 to 7.2) (0.1) (0.6 to 4.5) (0.6 to 4.5) (0.1) (0.7 to 4.2) (0.7 to 4.3) (0.1) (0.1) (0.6 to 3.2) (0.5 to 2.8)
All other 9 5.4 3.6 10 2.2 1.9 2 0.3 0.3 6 20 1.2 1.2
neonatal (0.3) (1.9 to 15.2) (1.2 to 10.7) (0.1) (0.8 to 6.0) (0.7 to 5.2) (0.0) (0.1 to 1.6) (0.1 to 1.5) (0.1) (0.1) (0.5 to 3.0) (0.5 to 3.0)
deaths
All percentages calculated relative to appropriate denominators (see methods).
*Reference category for odds ratios was women with interpregnancy interval of 18-23 months.
†Adjusted for maternal age, marital status, height, socioeconomic deprivation category, smoking, previous birth weight vigesimal, and previous caesarean section.

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Table 4 Interpregnancy interval, maternal age, other demographic factors, and risk of adverse obstetric outcome
Odds ratios (95% CI) for interpregnancy interval <6 months
Outcome Crude Adjusted 1
Delivery 24-32 weeks 3.1 (1.9 to 4.9) 2.3 (1.4 to 3.8)
Delivery 33-36 weeks 2.0 (1.6 to 2.4) 1.7 (1.3 to 2.1)
Neonatal death 5.4 (1.9 to 15.2) 3.8 (1.3 to 11.0)
unrelated to
congenital
abnormality or
rhesus
Adjusted 1=adjusted only for maternal age or interpregnancy interval; adjusted 2=adjusted only for maternal smoking, socioeconomic deprivation, height, previous birth weight vigesimal, and
previous caesarean section; adjusted 3=adjusted for maternal smoking, socioeconomic deprivation, height, previous caesarean section, birth weight vigesimal, and maternal age or interpregnancy
interval.
val was an independent risk factor for extremely
preterm birth, moderately preterm birth, and neonatal
death not due to congenital abnormality. The
association occurred even among women whose first
pregnancy was a term live birth and persisted after
adjustment for maternal age, marital status, height,
socioeconomic deprivation category, smoking, previ-
ous birth weight vigesimal, and previous caesarean sec-
tion. The association was specific to preterm birth and
neonatal death, as no association existed between a
short interpregnancy interval and the risk of delivering
a growth restricted infant and the confidence intervals
were sufficiently narrow to exclude even a weak associ-
ation. When we examined the outcome of all first
births in relation to the subsequent interpregnancy
interval, women with a short interpregnancy interval
had a significant excess of intrauterine growth
restriction, preterm birth, and perinatal deaths in their
first births. Indeed, approximately 10% of women with
an interval of less than six months had a first birth that
had ended in perinatal death, compared with less than
1% of women with an interval of 18-23 months. These
observations are consistent with previous studies and
underline the importance of excluding women with
complications in their first birth when examining asso-
ciations between interpregnancy interval and the
outcome of the second birth.11
An association has previously been shown between
maternal age less than 20 years at the time of the sec-
ond birth and adverse obstetric outcome.23 In the
present study we could show that this association was
independent of interpregnancy interval and complica-
tions of the first pregnancy. However, the association
between maternal age less than 20 years and adverse
outcome was attenuated by adjustment for marital
status, socioeconomic deprivation category, smoking
status, height, previous birth weight vigesimal, and pre-
vious caesarean section, although a statistically
significant association persisted in multivariate analysis
(table 4). We cannot exclude the possibility that mater-
nal age less than 20 years is a marker for some other
environmental factor. However, it is unlikely that the
associations with a short interpregnancy interval were
due to unmeasured or residual confounding. Firstly,
after adjustment for maternal age, adjustment for
other maternal factors had very little effect (table 4).
Secondly, the strength of the association was virtually
unchanged when we confined the analysis to married,
non-smoking women aged 25 and above. Thirdly, no
statistically significant first order interactions occurred
between a short interpregnancy interval and other
maternal factors. Finally, the association was specific
for preterm birth and neonatal death. No association
BMJ VOLUME 327 9 AUGUST 2003 bmj.com
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Papers
Odds ratios (95% CI) for age <20 years
Adjusted 2 Adjusted 3 Crude Adjusted 1 Adjusted 2 Adjusted 3
2.5 (1.5 to 4.0) 2.2 (1.4 to 3.6) 4.0 (2.6 to 6.2) 3.2 (2.0 to 5.1) 2.6 (1.6 to 4.2) 2.0 (1.2 to 3.4)
1.7 (1.4 to 2.1) 1.6 (1.3 to 2.0) 2.3 (1.9 to 2.9) 2.2 (1.7 to 2.7) 1.6 (1.3 to 2.1) 1.5 (1.2 to 2.0)
4.3 (1.5 to 12.3) 3.6 (1.2 to 10.7) 8.4 (3.2 to 22.2) 5.6 (2.0 to 15.9) 5.0 (1.6 to 15.7) 3.5 (1.0 to 11.6)
existed between a short interpregnancy interval and
delivering a small for gestational age baby. In contrast,
a high socioeconomic deprivation category (that is,
more deprived) was significantly associated with deliv-
ering a small for gestational age baby in multivariate
analysis (data not shown).
The lack of association between interpregnancy
interval and growth restriction also suggests that the
relation between a short interpregnancy interval and
other adverse outcomes is unlikely to be due to deple-
tion of maternal nutritional reserves. A specific associ-
ation between a short interpregnancy interval and
preterm birth is biologically plausible. The control of
parturition is thought to be mediated by a two step
process of activation and stimulation.24 Activation is
defined as the up regulation of expression of a range of
contraction associated proteins, such as G protein cou-
pled receptors, in the weeks leading up to term. Stimu-
lation is defined as the process by which synthesis and
release of natural agonists for these receptors, such as
prostaglandins, initiates uterine contraction. We
hypothesise that failure to allow expression of contrac-
tion associated proteins to return to prepregnancy
levels may be the mechanism by which a short
interpregnancy interval predisposes to preterm birth.
We propose that women should be informed of a
small but significantly elevated risk of preterm birth
What is already known on this topic
Women with a short interval between pregnancies
are at increased risk of obstetric complications
These women also differ in their previous obstetric
complications and demographic characteristics
Whether the increased risk of adverse outcome
after a short interpregnancy interval is merely due
to confounding by obstetric and demographic
associations is unclear
What this study adds
Women with short intervals between pregnancies
are much more likely to have had complicated
first births and to have demographic risk factors
for obstetric complications
Even among women with an uncomplicated first
birth and after adjustment for maternal
demographics, a short interpregnancy interval was
associated an increased risk of preterm birth and
neonatal death
page 5 of 6
 RETURN TO TABLE OF CONTENTS
Papers
and perinatal death when they conceive shortly after a
birth. Contraceptive advice should be targeted towards
women who are most likely to have a subsequent short
interpregnancy interval—namely, teenagers and
women who have just experienced a perinatal loss.
Contributors: GCSS had the original concept, reviewed
previous publications, undertook the statistical analyses, and
wrote the initial draft of the paper. JPP interpreted the results
and contributed to the draft of the paper. RD performed the
linkage and extracted the data. All authors edited and approved
the final version of the paper. GCSS is the guarantor.
Funding: None.
Competing interests: None declared.
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2 Lieberman E, Lang JM, Ryan KJ, Monson RR, Schoenbaum SC. The
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5 Basso O, Olsen J, Knudsen LB, Christensen K. Low birth weight and pre-
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6 Khoshnood B, Lee KS, Wall S, Hsieh HL, Mittendorf R. Short interpreg-
nancy intervals and the risk of adverse birth outcomes among five racial/
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Epidemiology 1999;10:250-4.
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9 Fuentes-Afflick E, Hessol NA. Interpregnancy interval and the risk of
premature infants. Obstet Gynecol. 2000;95:383-90.
10 Zhu BP, Haines KM, Le T, McGrath-Miller K, Boulton ML. Effect of the
interval between pregnancies on perinatal outcomes among white and
black women. Am J Obstet Gynecol 2001;185:1403-10.
11 Erickson JD, Bjerkedal T. Interpregnancy interval: association with birth
weight, stillbirth, and neonatal death. J Epidemiol Community Health
1978;32:124-30.
12 Klebanoff MA. Short interpregnancy interval and the risk of low
birthweight. Am J Public Health 1988;78:667-70.
13 Kaharuza FM, Sabroe S, Basso O. Choice and chance: determinants of
short interpregnancy intervals in Denmark. Acta Obstet Gynecol Scand
2001;80:532-8.
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McIlwaine GM, eds. Perinatal audit and surveillance. London: Royal
College of Obstetricians and Gynaecologists, 1980:39-51.
15 McIlwaine GM, Dunn FH, Howat RC, Smalls M, Wyllie MM,
MacNaughton MC. A routine system for monitoring perinatal deaths in
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16 Information and Statistics Division NHS Scotland. Scottish perinatal and
infant mortality and morbidity report 2001. Edinburgh: Common Services
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spimmr/SPIMMR-_2001.pdf)
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growth retardation: a British approach. In: Chervenak FA, Isaacson GC,
Campbell S, eds. Ultrasound in obstetrics and gynaecology, vol 2. Boston:
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approach. Br J Obstet Gynaecol 1986;93:1204-12.
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1999;341:660-6.
(Accepted 18 June 2003)
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Original Research ajog.org

OBSTETRICS
Relationship of trimester-specific smoking patterns and
risk of preterm birth
Elizabeth Moore, DO; Kaitlin Blatt, BS; Aimin Chen, MD, PhD; James Van Hook, MD; Emily A. DeFranco, DO, MS

BACKGROUND: In 2011, the US national rate of smoking early in
pregnancy was 11.5%. Unfortunately, our home state of Ohio had a rate
twice as high at 23%. Smoking in pregnancy remains one of the most
important modifiable risk factors for pregnancy complications, specifically
preterm birth.
OBJECTIVE: The objective of the study was to quantify the preterm
birth risk to various trimester-specific smoking behaviors.
STUDY DESIGN: The study was a population-based, retrospective
cohort study of singleton non-anomalous live births, using Ohio birth re-
cords 2006 to 2012. Preterm birth rates were compared between non-
smokers and women who smoked in the preconception period only,
those who quit smoking after the 1st and 2nd trimesters, and those who
smoked throughout pregnancy. Multivariate logistic regression quantified
the risk of smoking with cessation at various times in pregnancy and
preterm birth risk, adjusted for maternal race, education, age, Medicaid
use, marital status, and parity. A stratified analysis was performed on the
basis of preterm birth subtype: spontaneous preterm birth versus indicated
preterm birth. We also performed an additional analysis stratifying for
maternal race using the 2 largest categories of race (non-Hispanic white
and non-Hispanic black).
RESULTS: Of the 913,757 birth records analyzed, nearly 25% of the
women reported some smoking behavior on the birth certificate data. Of
smokers, less than half quit during pregnancy (38.8% vs 61.2% smoked
throughout pregnancy). Early quitters had a similar preterm birth rate
compared with non-smokers. Women who smoked through the 1st
trimester only did not have a significant increase in their overall preterm
birth odds ratio <37 weeks; however, it did increase the odds of extreme
preterm birth <28 weeks by 20% (adjusted odds ratio, 1.20; 95% con-
fidence interval [CI], 1.02, 1.40). Quitting late in pregnancy resulted in the
highest odds ratio increase: 70% for preterm birth <37 weeks (adjusted
odds ratio 1.70; CI, 1.60, 1.80), even after adjustment for the confounding
influences. Quitting smoking early in pregnancy after the 1st trimester did
not increase the overall risk of spontaneous or indicated preterm birth <37
weeks significantly. However, quitting after the 1st trimester was asso-
ciated with a significant increase in risk of extreme spontaneous preterm
birth <28 weeks, an effect not seen with indicated preterm birth <28
weeks. Delaying cessation until late in pregnancy—after the 2nd
trimester—was associated with the highest risk increases, 65% increased
odds of spontaneous and 78% increase in odds of indicated preterm
births. The rate of preterm births to non-Hispanic black mothers was
increased in all categories over those of non-Hispanic white mothers. The
relative influence of smoking cessation in pregnancy was similar in black
compared with white mothers. The effect modification in the regression
model was analyzed and revealed no significant interaction between race
and smoking patterns on preterm birth risk.
CONCLUSION: Smoking throughout pregnancy is associated with an
increased risk of preterm birth. However, quitting early in pregnancy ne-
gates this risk. Widespread programs aimed at smoking cessation early in
pregnancy could have a significant impact on reducing the rate of preterm
birth nationally.

B oth tobacco smoking and preterm

birth are significant global health
problems.1,2 Recent estimations in high-
income countries suggest implementa-
tion of maternal smoking cessation along
with other effective preventive ap-
proaches such as progesterone supple-
mentation, cervical cerclage placement,
decreasing non-medically indicated ce-
sarean section and labor induction, and
limiting multiple embryo transfer in
assisted reproductive technology may
reduce the rate of preterm birth by as
Cite this article as: Moore E, Blatt K, Chen A, et al.
Relationship of trimester-specific smoking patterns and
risk of preterm birth. Am J Obstet Gynecol 2016;
215:109.e1-6.
0002-9378/$36.00
ª 2016 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ajog.2016.01.167
much as 5% by the end of 2015.3 Preterm
birth <37 weeks is a strong predictor of
perinatal and infant mortality in the
United States and also contributes to
serious long-term morbidities, including
neurological handicaps as well as finan-
cial burdens on families and healthcare
systems.4-6
Smoking is one of the most important
modifiable risk factors for the reduction
of pregnancy complications. In 2011, the
prevalence of smoking early in preg-
nancy in Ohio was 23%, twice as high
compared with the US national rate of
11.5%.7 This high rate has been attrib-
uted to a variety of factors; however,
public health programs have been put in
place to target pregnant smokers.8,9
Because of the high rate of smoking in
pregnancy in our home state, we aim to
quantify the influence of quitting
smoking at various times in pregnancy
on preterm birth risk. These data may be
used to assist in smoking cessation
counseling in pregnancy.
Materials and Methods
The Human Subjects Institutional Re-
view Board of the Ohio Department of
Health approved the protocol for this
study and provided a de-identified set of
data for analysis that included birth
certificate data on 1,034,552 live births
that occurred in Ohio over a 7-year
period (2006e2012). This study was
exempt from review by the Institutional
Review Board at the University of Cin-
cinnati, Cincinnati, Ohio. All Ohio birth
records used the newest (2003) version
of the national birth certificate begin-
ning in 2006.10
We performed a population-based,
retrospective cohort study aimed to
compare various trimester specific

JULY 2016 American Journal of Obstetrics & Gynecology 109.e1


Original Research OBSTETRICS
maternal self-reported smoking behav-
iors during pregnancy with preterm birth
rates. The US birth certificate contains
data on maternal tobacco smoking dur-
ing 4 time periods: “3 months before
pregnancy,” “first 3 months of preg-
nancy,” “second 3 months of pregnancy,”
and “third trimester of pregnancy.”8
From this data, study subjects were
categorized into 1 of 5 exposure groups,
based on their smoking behaviors: “non-
smokers,” “smoked preconception only”
(smoked only in the 3 months prior to
conception but not in any trimester),
“smoked through 1st trimester” (smoked
preconception and the 1st trimester but
not in the 2nd or 3rd trimester), “smoked
through 2nd trimester” (smoked pre-
conception and the first 2 trimesters, but
not the 3rd trimester), and “smoked
throughout pregnancy” (smoked pre-
conception and in all trimesters).
Smoking
1 cigarette per day was
considered a smoker for the purpose of
this study. We performed additional
sensitivity analyses defining smokers us-
ing a threshold of
5 cigarettes per day.
Non-smokers comprised the referent
group for exposure group comparisons.
Our analyses were limited to
singleton, non-anomalous live births
between 20 and 42 weeks of gestation
with available data on maternal smoking
during pregnancy. Gestational age was
defined using the US Vital Statistics Birth
Certificate variable gest_comb, which is
the clinician’s best estimate of gestational
age using a combination of the last
menstrual period and earliest ultrasound
measurement.11 The primary outcome
of this study was preterm birth <37
weeks. We then stratified the outcomes
into subcategories of preterm birth:
extremely preterm (20e27 weeks) and
preterm (28e36 weeks). Term births, 37
to 42 weeks, comprised the referent
group for outcome comparisons.
We performed a stratified analysis based
on preterm birth subtype: spontaneous
preterm birth (SPTB) versus indicated
preterm birth (IPTB). Indicated PTB
included births at <37 weeks complicated
by intrauterine growth restriction (IUGR),
preeclampsia, eclampsia, or births that
occurred <37 weeks following induction
of labor as recorded in the birth certificate.
109.e2 American Journal of Obstetrics & Gynecology JULY 2016
RETURN TO TABLE OF CONTENTS
IUGR was defined as birthweight less
than the 10th percentile, based on a
widely used US reference.12 Preterm births
not categorized as indicated were consid-
ered spontaneous preterm births for
the purposes of this study. We also per-
formed an additional analysis stratifying
for maternal race using the 2 largest cate-
gories of race (non-Hispanic white and
non-Hispanic black). Additionally, we
tested for effect modification and found
no significant interaction between race
and smoking patterns in preterm birth
risk.
After exclusions of birth <20 or >42
weeks, missing gestational age, fetal
anomalies, and twins or higher-order
multiples, the cohort used for this anal-
ysis comprised 927,424 live births. Of the
other variables that were analyzed
(maternal age, race, educational attain-
ment, and smoking habits), there was
minimal missing data (<2%). Medicaid
enrollment had slightly higher amounts
of missing data (4%). Smoking behavior
was largely reported; only 0.7% (n ¼
6254) of birth records in Ohio had
missing data on smoking, and 0.8% (n ¼
7413) of the subjects had intermittent
smoking habits that did not correspond
with one of the 5 exposure categories
defined for this study. Those cases were
not included in this analysis.
Comparisons of dichotomous variables
were performed with c2 tests and
continuous variables were compared us-
ing ANOVA. Multivariate logistic regres-
sion quantified the odds of preterm birth
among each of the smoking behavior
groups compared with non-smokers
(referent) after adjustment for the con-
founding influences of maternal race,
maternal age, maternal education, marital
status, Medicaid funded delivery, and
parity. Covariates for the adjusted models
were selected on the basis of significant
differences noted among exposure groups
as well as biologic plausibility. Analyses
were performed using STATA 12.1 soft-
ware (StataCorp, College Station, Texas).
Comparisons were considered statistically
significant if the P value was <.05.
Results
Of the 913,757 birth records included in
this study, nearly 25% (n ¼ 216,491,
ajog.org
23.7%) of the women in our study
population reported some smoking
behavior on the birth certificate data.
Women who smoked preconception
only comprised 5.8% (n ¼ 53,355) of the
study cohort; 2.4% (n ¼ 21,803) smoked
through the 1st trimester, 1.0% (n ¼
8797) smoked through the 2nd
trimester, and 14.3% (n ¼ 132,536)
smoked throughout pregnancy. Of
women who smoked, less than half quit
smoking during pregnancy (n ¼ 83,955;
38.8% vs 132,536 who smoked
throughout pregnancy; 61.2%). Of
quitters, more women quit early in
pregnancy compared with quitting in the
2nd or 3rd trimester (P <.01). Summary
statistics regarding quantity of smoking
among this population are reported
elsewhere.13
Women who smoked throughout
pregnancy were more likely of non-
Hispanic white race, maternal age <20
years, low educational attainment, were
unmarried, and had Medicaid funded
medical care. Women who smoked
through the 2nd trimester had signifi-
cant increases in rates of preterm birth,
most notably among the following high
risk groups: non-Hispanic black race
(23.9%), maternal age >35 years
(29.4%), and low educational attain-
ment (21.8%); where the percentage
equals the percent of preterm birth rates
for the corresponding high-risk group.
Women of advanced maternal age (>35
years) had nearly a 3-fold increased risk
of preterm birth if they smoked through
the 2nd trimester compared with non-
smoking women of the same age group
(Table 1).
The preterm birth (PTB) rate in non-
smokers among our study cohort of
singleton non-anomalous births was
10%. Early quitters (smoked preconcep-
tion only) had a similar PTB rate
compared with non-smokers (9.6%),
although statistically significant at
P < .01. Women who smoked through
the 1st trimester only then quit did not
have a significant increase in their overall
PTB risk <37 weeks (11.4%) compared
with non-smokers (adjusted odds ratio
[adj OR], 1.02 [0.98, 1.07]); however, it
did increase the risk of extreme preterm
birth <28 weeks by 20% (adj OR, 1.20
 RETURN TO TABLE OF CONTENTS
ajog.org OBSTETRICS Original Research

TABLE 1
Maternal characteristics
Smoked Smoked through Smoked through Smoked throughout
Non-smokers preconception only 1st trimester 2nd trimester pregnancy
n ¼ 697,266 n ¼ 53,355 n ¼ 21,803 n ¼ 8797 n ¼ 132,536
Demographic factors
Maternal race
Non-Hispanic white 517,166 (8.7%) 44,435 (8.8%) 17,728 (10.4%) 7130 (17.0%) 114,230 (13.0%)
Non-Hispanic black 120,430 (15.3%) 6534 (14.9%) 3123 (16.9%) 1355 (23.9%) 14,920 (18.6%)
Hispanic 36,657 (11.7%) 1858 (9.0%) 753 (10.5%) 249 (18.1%) 2564 (13.8%)
Other 21,805 (9.1%) 471 (10.6%) 169 (9.5%) 48 (12.5%) 651 (12.4%)
Age group, years
<20 63,110 (14.1%) 6163 (10.3%) 3580 (11.4%) 1524 (17.7%) 16,883 (12.9%)
20e34 538,815 (9.4%) 43,783 (9.2%) 17,068 (11.0%) 6777 (17.3%) 106,755 (13.3%)

35 95,341 (10.7%) 3409 (12.5%) 1155 (17.1%) 496 (29.4%) 8898 (18.3%)
Socioeconomic factors
Less than high school diploma 94,378 (13.2%) 7171 (11.3%) 4243 (12.6%) 2192 (21.8%) 42,280 (15.3%)
Unmarried 238,063 (13.4%) 29,475 (10.3%) 15,005 (11.9%) 6533 (18.2%) 94,084 (14.1%)
Medicaid 239,827 (10.8%) 26,265 (9.1%) 13,141 (11.1%) 5709 (18.1%) 90,035 (13.8%)
Data listed as n (rate of preterm birth in each group).
All comparisons are statistically significant at P value .001 for the c2 statistic corresponding to the 5esmoking group comparison for each maternal characteristic in this table.
Dichotomous variables are presented as percent of preterm births for corresponding smoking group.
Moore et al. Relationship of trimester-specific smoking patterns and risk of preterm birth. Am J Obstet Gynecol 2016.

[1.02, 1.40]). Smoking through the 2nd
trimester, then quitting late in pregnancy,
resulted in the highest risk increase (70%
for PTB <37 weeks [adj OR, 1.70; 95%
CI, 1.60, 1.80]) compared with non-
smokers, even after adjustment for the
confounding influences of maternal race,
maternal age, maternal education,
Medicaid-funded medical care, marital
status, and parity (Table 2).
After redefining smokers as those who
reported using 5 cigarettes or more per
day, we performed a sensitivity analysis
that generated similar results. With the
use of this new definition, the rate of
PTB in early quitters and those who quit
after the 1st trimester were nearly iden-
tical to the original analysis (9.4% and
11.5%, respectively), which did not
significantly increase their PTB risk from
the non-smokers (adj OR, 1.03; CI, 0.98,
1.09). Women who smoked
5 ciga-
rettes per day and did not quit smoking
until after the 2nd trimester had an
increased risk of PTB <37 weeks of 90%
(adj OR, 1.90; CI, 1.76, 2.04), again
similar to our initial analysis defining
smokers as
1 cigarette per day.
Preterm birth rates related to each
smoking behavior were stratified by
maternal race (non-Hispanic black race
and non-Hispanic white race). The rate
of PTB to non-Hispanic black mothers
was increased in all categories over those
of non-Hispanic white mothers. In fact,
the rate of PTB in non-Hispanic black
mothers was nearly double (15.3% vs
8.7%) compared with that of non-
Hispanic white mothers. The relative
influence of smoking cessation in preg-
nancy was similar in black compared
with white mothers, respectively (for
cessation after the 1st trimester: adj OR,
1.10 [0.99, 1.21] vs adj OR, 1.06 [1.01,
1.12]; cessation after 2nd trimester: adj
OR, 1.59 [1.40, 1.82] vs adj OR, 1.81
[1.70, 1.94]; and smoked throughout
pregnancy: adj OR, 1.15 [1.10, 1.21] vs
adj OR, 1.28 [1.26, 1.32]) (data not
shown in Table 2).
When stratified by preterm birth
subtype, smoking had a similar influence
on risk of both indicated and sponta-
neous preterm births. Quitting smoking
early in pregnancy after the 1st trimester
did not increase the overall risk of
spontaneous or indicated preterm birth
<37 weeks significantly, Table 3. How-
ever, quitting after the 1st trimester was
associated with a significant increase in
risk of extreme spontaneous PTB <28
weeks, an effect not seen with indicated
PTB <28 weeks. Delaying cessation until
late in pregnancy—after the 2nd
trimester—was associated with the
highest risk increases (65% increased
odds of spontaneous and 78% increase
in odds of indicated preterm birth).
Comment
Smoking in pregnancy has been widely
accepted as a significant risk factor for
preterm birth.14 As such, smoking
cessation reduces the risk of preterm
birth.15 Our large, population-based

JULY 2016 American Journal of Obstetrics & Gynecology 109.e3

 RETURN TO TABLE OF CONTENTS
Original Research OBSTETRICS ajog.org

study includes nearly a million women

who live in a state that has a rate of

1.21 (1.19, 1.24)

0.90 (0.83, 0.97)

1.24 (1.21, 1.26)
smoking in pregnancy twice as high as
the national average, an area that needs

(95%CI)
Adj ORa
urgent attention to smoking cessation
interventions. We found that women
who quit smoking early in pregnancy,
either in the 1st or 2nd trimester, had

18,053 (13.62)

17,183 (12.96)
870 (0.66)
similar risks of PTB compared with non-
throughout
pregnancy
smokers. However, delayed smoking
Smoked

cessation until late in pregnancy, after

the 2nd trimester, or continued smoking
throughout pregnancy, were associated
1.70 (1.60, 1.80)

1.46 (1.37, 1.55)

with significant increases in the risk of
PTB. We also observed a notable further
(95%CI)
Adj ORa

increased risk of preterm birth in women

with concomitant PTB factors: 23.9% in
non-Hispanic black women, 29.5% in
All comparisons are statistically significant at P value .001 for the c statistic corresponding to the 5esmoking group comparison for each maternal characteristic in this table.
Quit after 2nd

1590 (18.07)

1268 (14.41)

women of advanced maternal age (>35

Trimester

years), and 21.8% in women with low

educational attainment if cessation did
n/a

not occur until after the 2nd trimester.

Similar to the study by Hodyl et al,16
1.02 (0.98, 1.07)

1.20 (1.03, 1.40)

1.01 (0.96, 1.05)

we too found that early smoking cessa-

tion reduces a woman’s risk of preterm
(95%CI)
Adj ORa

birth to levels comparable with a non-

smoker and with continuation of
Adjusted for mother’s race, mother’s education, mother’s age, Medicaid, marital status, and parity. Anomalies and multiples excluded.

smoking throughout pregnancy the rates

of preterm and very preterm births are
Quit after 1st

0.91 (0.88, 0.94) 2477 (11.36)

0.91 (0.88, 0.94) 2275 (10.43)

202 (0.93)

Moore et al. Relationship of trimester-specific smoking patterns and risk of preterm birth. Am J Obstet Gynecol 2016.

increased. However, this previously

Trimester

published study did not distinguish be-

tween cessation in the 2nd or 3rd
trimester with smoking throughout
0.87 (0.77, 0.98)

pregnancy. Additionally, our study is

unique in that it is a very large (n ¼
Preterm birth risk associated with smoking in pregnancy

(95%CI)
Adj ORa

927,424), population-based study in the

United States, which allows for better
Dichotomous variables are presented as percent of n for corresponding smoking group.

generalizability. Numerous other studies

have shown analogous results related to
Preconception

early smoking cessation and preterm risk

5096 (9.55)

4784 (8.97)
312 (0.58)

relative to that of a non-smoker.17-19

Smoked

Polakowski et al18 similarly used birth

only

certificate data; however, their study only

evaluated preterm births >28 weeks.
Never-smokers

69,794 (10.01)

28e36 weeks, n (%) 65, 564 (9.40)

4230 (0.61)

Our results show a 20% increase in

extreme preterm births (20e27 weeks) if
cessation occurred after the 1st trimester.
Delayed smoking cessation until late
in pregnancy is associated with increased
Overall PTB <37 weeks

20e27 weeks, n (%)

Subcategories of PTB
<37 weeks, n (%)

risk of both preterm subtypes, both

indicated and spontaneous preterm
Preterm birth

births. Smoking in pregnancy is known

TABLE 2

to increase the risk of IUGR, which is a

significant contributor to indicated
preterm births. IUGR risk is increased
a

even if smoking cessation occurs in

109.e4 American Journal of Obstetrics & Gynecology JULY 2016

 RETURN TO TABLE OF CONTENTS
ajog.org OBSTETRICS Original Research

pregnancy, with risk highest for those

who quit later in pregnancy.13 This study

1.20 (1.17, 1.22)

1.25 (1.22, 1.28)

0.93 (0.84, 1.02)

1.22 (1.18, 1.26)

1.18 (1.14, 1.22)

0.73 (0.69, 0.78)
demonstrates that smoking also nega-
tively influences the risk of spontaneous

(95% CI)
Adj ORa
preterm births overall. Even quitting in
the 2nd trimester may be too late to
protect from the influence of smoking
on extreme spontaneous preterm birth

650 (0.56)

5319 (4.03)

5592 (4.66)
1279 (1.10)
12,299 (9.31)

11,245 (8.94)
Throughout

<28 weeks, as evidenced by a 20%

pregnancy
Smoked

increased PTB odds even after adjust-

ment for other preterm birth risk factors.
One strength of our study is that it
1.65 (1.54, 1.77)

1.37 (1.26, 1.48)

1.78 (1.62, 1.96)

1.66 (1.51, 1.83)

analyzes a large population base by use of
birth certificate data. The newest version
(2003 revision) of the birth certificate
(95% CI)
Adj ORa

was used which allowed us to perform a

detailed evaluation of each woman’s
smoking status for each trimester.20
Quit after 2nd

1058 (12.06)

All comparisons are statistically significant at P value .001 for the c statistic corresponding to the 5esmoking group comparison for each maternal characteristic in this table. Furthermore, the population-based
767 (9.62)

505 (5.76)

508 (6.58)
trimester

contemporary basis allows for general-

izability to most pregnancies cared for in
n/a

n/a

the United States. To our knowledge, this

study is the largest to look at preterm
1.03 (0.97, 1.08)

1.02 (0.96, 1.08)

1.20 (1.00, 1.43)

1.01 (0.94, 1.09)

0.99 (0.92, 1.07)

0.93 (0.82, 1.05)

births and its association with trimester-

Influence of smoking cessation in pregnancy on spontaneous and indicated preterm births

specific smoking patterns. Specifically,

(95% CI)
Adj ORa

our study analyzes the risk of extreme

preterm births that is not reported in
Adjusted for mother’s race, mother’s education, mother’s age, Medicaid, marital status, and parity. Anomalies and multiples excluded.

previous studies. We recognize that our

Quit after 1st

study does have limitations, however.

1700 (7.81)

1472 (7.08)
146 (0.75)

744 (3.42)

792 (3.94)
283 (1.44)

Moore et al. Relationship of trimester-specific smoking patterns and risk of preterm birth. Am J Obstet Gynecol 2016.

Birth certificate data are not designed

trimester

for this particular research purpose.

Concomitant data regarding alcohol use,
drug use, and secondhand smoke expo-
0.90 (0.87, 0.93)

0.88 (0.77, 1.02)

0.92 (0.87, 0.97)

0.91 (0.87, 0.96)

0.85 (0.78, 0.93)

sure were not available from our data

0.90 (0.87 0.94)

source and therefore could not be

accounted for in our adjusted analyses.
(95% CI)
Adj ORa

Data on the etiology of preterm birth,

Dichotomous variables are presented as percent of n for corresponding smoking group.

that is, spontaneous versus indicated, are

not directly collected on the birth cer-
Preconception

tificate. However, our method of

3476 (6.52)

3077 (5.99)

1546 (2.90)

1675 (3.35)
223 (0.46)

620 (1.27)
2

defining these categories from associated

Smoked

delivery characteristics resulted in dis-

only

tributions consistent with that known

from prospectively collected data.21
Never-smokers

Since smoking status on the birth re-

48,779 (7.00)

43,116 (6.43)
2994 (0.47)

20,183 (2.90)

22,230 (3.42)
8757 (1.38)

cords is self-reported, there may be an

element of under-reporting or misclas-
sification resulting in an underestimate
Spontaneous preterm birth

of our effect size estimates; however,

Indicated preterm births
Overall <37 weeks, n

Overall <37 weeks, n

28e36 weeks, n (%)
20e27 weeks, n (%)

28e36 weeks, n (%)

20e27 weeks, n (%)

studies have shown that self-reporting of

reproductive smoking behaviors have
been quite reliable.22,23 Last, we received
Preterm birth
TABLE 3

data on live births only. Stillbirths

occurring before 37 weeks account for
(%)

(%)

approximately 5% of preterm births.

a

Including only live births may

JULY 2016 American Journal of Obstetrics & Gynecology 109.e5


Original Research OBSTETRICS
underestimate the true burden of
smoking on preterm birth, especially if
smoking has a differential effect on per-
iviable preterm birth or stillbirth.24
This study reinforces the findings of
prior studies regarding smoking in preg-
nancy and preterm birth and adds depth
to our overall understanding of those
populations most strongly affected. Our
study provides novel information about
smoking behavior in each trimester spe-
cifically and its relationship to the rate of
preterm birth. Public health initiatives
and interventions should focus on early
smoking cessation as smoking beyond the
2nd trimester significantly increases the
overall risk of preterm birth and smoking
beyond the 1st trimester has a significant
risk on early preterm births <28 weeks.
Since preterm births have serious short-
and long-term effects (physically,
mentally, emotionally, and financially) on
these infants, their families, and those
caring for them, incorporating a “no
smoking in pregnancy” campaign or at
least early smoking cessation programs
focused on reproductive-age women are
imperative. n Retrieved July 2014 from http://www.cdc.gov/
Acknowledgments
This study includes data provided by the Ohio
Department of Health which should not be
considered an endorsement of this study or its
conclusions.
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Author and article information
From the Division of Maternal-Fetal Medicine, Depart-
ment of Obstetrics and Gynecology, University of Cin-
cinnati College of Medicine, Cincinnati, Ohio (Drs Moore,
Van Hook, and DeFranco); University of Cincinnati College
of Medicine, Cincinnati, Ohio (Ms Blatt); Department of
Environmental Health, University of Cincinnati College of
Medicine, Cincinnati, Ohio (Dr Chen); Center for Pre-
vention of Preterm Birth, Perinatal Institute, Cincinnati
Children’s Hospital Medical Center, Cincinnati, Ohio (Dr
DeFranco).
Received Sept. 30, 2015; revised Jan. 16, 2016;
accepted Jan. 20, 2016.
The authors report no conflict of interest.
Ms Blatt received research funding from an educa-
tional grant from the University of Cincinnati Department
of Obstetrics and Gynecology Women’s Health Scholars
Program. Dr DeFranco received research funding from
the Perinatal Institute, Cincinnati Children’s Hospital
Medical Center, Cincinnati, Ohio; March of Dimes Grant
22-FY14-470.
Corresponding author: Elizabeth Moore, DO.
mossineh@ucmail.uc.edu
 RETURN TO TABLE OF CONTENTS
Journal of Perinatology (2016) 00, 1–5
© 2016 Nature America, Inc. All rights reserved 0743-8346/16
www.nature.com/jp

ORIGINAL ARTICLE
Self-reported and laboratory evaluation of late pregnancy
nicotine exposure and drugs of abuse
ES Hall1,2, SL Wexelblatt1 and JM Greenberg1,2

OBJECTIVE: The objective of this study was to evaluate the prevalence of late pregnancy nicotine exposures, including secondhand
smoke exposures, and to evaluate the associated risk of exposure to drugs of abuse.
STUDY DESIGN: The study was a retrospective single-center cohort analysis of more than 18 months. We compared self-reported
smoking status from vital birth records with mass spectrometry laboratory results of maternal urine using a chi-square test. Logistic
regression estimated adjusted odds for detection of drugs of abuse based on nicotine detection.
RESULTS: Compared with 8.6% self-reporting cigarette use, mass spectrometry detected high-level nicotine exposures for 16.5% of
708 women (P o 0.001) and an additional 7.5% with low-level exposures. We identified an increased likelihood of exposure to drugs
of abuse, presented as adjusted odds ratios, (95% confidence interval (CI)), for both low-level (5.69, CI: 2.09 to 15.46) and high-level
(13.93, CI: 7.06 to 27.49) nicotine exposures.
CONCLUSION: Improved measurement tactics are critically needed to capture late pregnancy primary and passive nicotine
exposures from all potential sources.
Journal of Perinatology advance online publication, 7 July 2016; doi:10.1038/jp.2016.100

INTRODUCTION for nicotine intake including primary and secondary tobacco

The negative consequences of cigarette smoking and nicotine
exposure during pregnancy on perinatal outcomes including
preterm birth, low birth weight, stillbirth and infant death are
thoroughly documented.1–6 Associations between maternal
tobacco use, substance abuse and physical abuse have also been
reported.7,8 In 2010, more than 10% of women in the US reported
smoking cigarettes during the third trimester of pregnancy.9 Yet,
this estimate suffers from several limitations. First, previous studies
document rates of non-disclosure among smokers ranging from
5 to 73%, presumably owing to social pressure and recall bias,
particularly during pregnancy.10–14 Second, frequently cited
measures of pregnancy smoking derived from vital statistics are
based upon an estimated typical daily number of cigarettes
smoked. This measure does not incorporate other nicotine
product exposures (including cigars, cigarillos, electronic cigar-
ettes, smokeless tobacco such as chewing tobacco or snuff,
or medical nicotine from patches or gum). Finally, estimates of
pregnancy smoking do not measure secondhand cigarette
or other tobacco smoke exposures. Thus, the prevalence of
significant nicotine exposures during late pregnancy is potentially
much higher than 10%. Previous studies conclude that all nicotine
exposures including secondhand exposures (and not just those
originating from cigarettes) have potentially negative conse-
quences and should be avoided during pregnancy.15–17 Thus,
understanding the true rate of exposure to nicotine during
pregnancy, regardless of source, is an important public health
priority.
The objective of this study was to measure the prevalence of
late pregnancy nicotine exposures detected using a laboratory
validation strategy compared with self-reported measures cap-
tured from live birth certificates and vital statistics. As the
major proximate metabolite of nicotine, cotinine is a biomarker
exposures.18–20 Reliability of cotinine measurement has been
demonstrated previously using mass spectrometry analysis of
blood, urine, saliva, hair and nails.21–23 Cotinine has a reported
half-life of 16.6 h, but clearance has been reported as accelerated
in pregnant women with a half-life as short as 8.8 h.24 Even in
nonpregnant individuals, cotinine detection is limited to nicotine
exposures during the most recent 3 to 4 days.20 Thus, we focused
our analysis on detecting nicotine exposures during the last few
days of pregnancy. For the current analysis, we hypothesized that
self-reported cigarette use would underestimate late pregnancy
nicotine exposures compared with laboratory validation with mass
spectrometry. We also aimed to document low-level nicotine
exposures among the pregnant population using laboratory
measures. Finally, we sought to assess the differences in late
pregnancy exposures to drugs of abuse including opioids among
those testing positive for high- or low-level nicotine exposures.
Our findings offer a foundation for developing improved
strategies to evaluate public health campaigns aimed at smoking
cessation and reduction of other nicotine exposures during
pregnancy.
MATERIALS AND METHODS
We conducted a retrospective cohort analysis of self-reported, last
trimester cigarette smoking status and mass spectrometry cotinine
measurements generated from maternal urine samples obtained at the
time of admission for delivery at a single maternity hospital in Southwest
Ohio. The hospital was distinct in that mass spectrometry was used as the
default drug testing method as opposed to being used only for
confirmation testing following positive immunoassay test results. Analysis
data were derived from two deidentified data sources (laboratory data and
vital birth records) representing the same population of mothers during an
18-month study period—March 2014 to August 2015. This study was

1
Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA and 2Cradle Cincinnati, Cincinnati, OH, USA. Correspondence: Dr ES Hall, Perinatal Institute,
Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, ML7009, Cincinnati, OH 45229, USA.
E-mail: eric.hall@cchmc.org
Received 13 April 2016; revised 20 May 2016; accepted 3 June 2016
 RETURN TO TABLE OF CONTENTS
Late pregnancy nicotine exposures
ES Hall et al
2
Figure 1. Smoking question from the Ohio Mother’s Worksheet for Child’s Birth.30
reviewed and approved with a waiver of informed consent granted by the
Cincinnati Children’s Hospital Medical Center and Ohio Department of
Health Institutional Review Boards.
Laboratory data
To address rapid increases in intrauterine opioid exposure incidence
throughout Ohio,25 all maternity centers in the southwest region of the
state now use universal collection of maternal urine samples for drug
testing. Women are consented as part of the standard hospital admission
process. Samples are obtained at the time of parturition to facilitate
timely identification and treatment of infants at risk for withdrawal as a
consequence of opioid exposure. Positive tests for opioids triggers
inpatient clinical observation of the newborn for 72 to 96 h during which
time Finnegan scoring is initiated and nonpharmacologic care provided.
The hospital maternity unit-based social services provider is also consulted
to perform a risk assessment prior to infant discharge.26 Infants diagnosed
with neonatal abstinence syndrome are treated according to regional
guidelines.27
We obtained mass spectrometry laboratory results generated during the
study time frame, providing quantified measures of urine cotinine and
other drug exposures including tests for amphetamines, benzodiazepines,
barbiturates, cannabinoids, cocaine, muscle relaxants, short-acting opioids,
including heroin, long-acting opioids, including buprenorphine or
methadone, and phencyclidine. We defined polypharmacy as a positive
test result for two or more of the previously listed drug classes. Urine
samples were collected and mass spectrometry was conducted for the
majority of maternal admissions. Because the mass spectrometry
laboratory does not process samples on Sundays or holidays, urine
samples corresponding to vaginal deliveries on Saturdays or days
preceding holidays were tested on-site using an immunoassay test
instead, which does not include detection of nicotine exposure. These
exclusions represent approximately 10% of total deliveries and were not
deemed sufficient to bias our findings.
Previous studies have demonstrated that urine cotinine values seldom
exceed 100 ng ml − 1 from passive nicotine exposure alone and cotinine
levels in active smokers (including light smokers) typically reach a
threshold of 100 ng ml − 1 or more.28,29 In our analysis, cotinine
levels ⩾ 100 ng ml − 1 were interpreted as indicating high-level nicotine
exposures; levels ranging from 5 to 99 ng ml − 1 were categorized as low-
level exposures; and levels o5 ng ml − 1 were categorized as negative
exposures. High levels correspond to active use of tobacco products or
nicotine delivery devices during late pregnancy. Low levels could
correspond to secondary smoke exposure during late pregnancy or
complete cessation of nicotine exposure 3 to 4 days before delivery
subsequent to heavy use. Among the laboratory results, 37 positive tests
were recorded as ‘ ⩾ 250 ng ml − 1’ without precise values—these results
were excluded from mean, median and standard deviation calculations.
Demographics including race and ethnicity, insurance status and maternal
age were also obtained from administrative data associated with the
laboratory results. Race and ethnicity was missing from nine records in the
laboratory data set.
Vital birth records
The Ohio Department of Health provided anonymized vital birth statistics
containing race and ethnicity, insurance status and maternal age
measures. Records for all mothers who delivered a live born infant at
the study site during the 18-month study period were included. Race
and ethnicity values were missing from 10 vital birth records and insurance
status was missing from 3 records. Vital records also included a
Journal of Perinatology (2016), 1 – 5
self-reported measure of last trimester cigarette smoking status, which
was missing from four records. We used the third trimester smoking status
variable to represent last trimester smoking status for women with infants
born at ⩾ 27 weeks. For women who delivered at gestational age
o27 weeks (N = 5), the second trimester smoking status variable was used.
Smoking measures are obtained in Ohio using a birth certificate worksheet
completed by each mother after delivery (see Figure 1).30 Women who
reported any number of cigarettes on a ‘typical day’ during the last
trimester of pregnancy were further characterized into three subcate-
gories: Heavy smoker (20+ cigarettes per day), moderate smoker (10 to 19
cigarettes per day) or light smoker (o 10 cigarettes per day).31,32 Singleton
and multiple gestation pregnancies were included; however, each woman
was represented in the data set a single time using the birth record of the
firstborn infant for multiple gestation pregnancies.
Analysis
Demographics obtained through vital birth records were compared with
those obtained through laboratory administrative data to identify potential
differences between the two populations. We identified women
with nicotine exposures in each group comparing exposure rates and
demographics among those with exposures (by self-reported cigarette use
or mass spectrometry urine cotinine results). We used two-sided chi-square
tests for comparisons of categorical variables and t-tests to detect
differences in the continuous maternal age variable. Among delivering
mothers residing in the county in which the maternity hospital is located,
10.2% self-reported late pregnancy cigarette smoking in 2014.33 Using this
estimate, we determined that a sample of 600 women would provide
greater than 80% power (α = 0.05) to detect a 50% difference comparing
nicotine exposure detection methods in the study cohort.
Using laboratory test results, we also reported positive drug-detection
rates. Next, we constructed a logistic regression model including race and
ethnicity, insurance status, maternal age and nicotine exposure level to
calculate adjusted odds ratios with 95% confidence intervals (CIs) for
positive drug test results. Regressions were repeated for cannabinoid, any
opioid or polypharmacy exposures. All statistical analyses and calculations
(including assessment of model goodness of fit and verification that data
met assumptions for statistical tests) were conducted using SAS version 9.3
(SAS Institute, Cary, NC, USA) software.
RESULTS
Vital birth records were generated for 787 women who delivered a
live born infant at the study site during the 18-month study period.
The population was described as 17.9% black, non-Hispanic, 76.8%
white, non-Hispanic and 5.3% from another racial or ethnic group.
Medicaid insured 36.4% of mothers and 61.0% were privately
insured. The mean maternal age was 28.1 years. During the same
time frame, mass spectrometry was performed on urine samples
from a subcohort of 708 women (90.0% of women who delivered
during the study time frame). No differences were detected in race
and ethnicity (P = 0.98), insurance status (P = 0.92) or maternal age
(P = 0.66) between groups.
According to vital statistics, 68 of 787 women (8.6%) self-
reported any amount of cigarette smoking during their final
trimester of pregnancy. Smoking status was further categorized as
4.0% light smokers, 2.8% moderate smokers and 1.9% heavy
smokers. Among 708 women whose samples were laboratory
tested, 117 (16.5%) tested positive for high-level nicotine exposure
© 2016 Nature America, Inc.
 RETURN TO TABLE OF CONTENTS
Late pregnancy nicotine exposures
ES Hall et al
(⩾100 ng ml − 1) (mean ± s.d.: 922.1 ± 591.2 ng ml − 1, median:
770 ng ml − 1). An additional 53 samples (7.5%) tested positive
for low-level nicotine exposures (5 to 99 ng ml − 1) (mean ± s.d.:
24.1 ± 19.1 ng ml − 1, median: 19 ng ml − 1). Altogether, laboratory
testing identified nicotine exposures in 170 women (24.0%)
(mean ± s.d.: 564.2 ± 635.7 ng ml − 1, median: 349 ng ml − 1). Distri-
bution of laboratory values is shown in Figure 2 with values
ranging from 4 to 2820 ng ml − 1.
Compared with self-reported cigarette smoking from vital
statistics, laboratory testing represented a significant increase in
the detection of high-level nicotine exposure (8.6 vs 16.5%,
P o0.001) or any nicotine exposure (8.6 vs 24.0%, P o 0.001). We
also identified higher rates of nicotine exposure comparing high-
level detection by mass spectrometry vs maternal self-report
among black, non-Hispanic women (7.9 vs 21.1%, P = 0.004), white,
non-Hispanic women (9.5 vs 15.7%, P = 0.002) and among
Medicaid insured (15.8 vs 30.7%, P o0.001) as well as privately
insured women (4.2 vs 8.0%, P = 0.02) (Table 1). No significant
differences were detected in composition of race and ethnicity
(P = 0.27), insurance status (P = 0.87) or in maternal age (P = 0.35)
comparing women who self-reported cigarette use with women
with high-level laboratory detected levels of cotinine.
3
Laboratory testing detected 67 of 708 women (9.5%) with
positive results for exposure to at least one of the previously
enumerated drugs of abuse. Cannabinoids accounted for the
largest number of positive tests (N = 37, 5.2%) followed by opioids
including heroin (N = 27, 3.8%). Fifteen women (2.1%) tested
positive for multiple substances (Table 2).
Both low and high levels of nicotine exposure were predictors
of additional drug exposure (low level adjusted odds ratio: 5.69,
95% CI: 2.09 to 15.46; high-level adjusted odds ratio: 13.93, 95% CI:
7.06 to 27.49). High-level nicotine exposure was also predictive of
cannabinoid, opioid and polypharmacy exposures (Table 3).
Low-level nicotine exposure was associated with an increased
rate of cannabinoid exposure. In addition, controlling for nicotine
exposure, Medicaid insured women were more likely to test
positive for any drug or opioids than privately insured women.
Black, non-Hispanic women were less likely than white, non-
Hispanic women to test positive for opioids. No other racial
differences in drug detection were identified. Finally, likelihood of
positive drug detection increased with maternal age.
DISCUSSION
Compared with 8.6% of mothers self-reporting cigarette use,
laboratory mass spectrometry detected primary nicotine

Table 2. Mass spectrometry laboratory drug test results for 708

women

Positive drug test N (%)

Any drug 67 (9.5)

Amphetamines 1 (0.1)
Benzodiazepines 5 (0.7
Barbiturates 2 (0.3)
Cannabinoids 37 (5.2)
Cocaine 9 (1.3)
Muscle relaxants 0 (0.0)
Any opioid 27 (3.8)
Short-acting opioids including heroin 25 (3.5)
Long-acting opioids (buprenorphine or 5 (0.7)
methadone)
Phencyclidine 0 (0.0)
Figure 2. Distribution of study cohort low- and high-level laboratory Polypharmacy 15 (2.1)
cotinine levels. (NOS, not otherwise specified).

Table 1. Comparison of self-reported and laboratory-detected nicotine exposure rates by race and ethnicity as well as insurance status

Characteristic Mass spectrometry Low-level High-level Any exposure Vital birth Self-reported Pa
tested exposure exposure records cigarette use
N N (%) N (%) N (%) N N (%)

All measured 708 53 (7.5) 117 (16.5) 170 (24.0) 787 68 (8.6) o 0.001

Race and ethnicity

Black, non-Hispanic 128 19 (14.8) 27 (21.1) 46 (35.9) 139 11 (7.9) 0.004
White, non- 535 31 (5.8) 84 (15.7) 115 (21.5) 597 57 (9.5) 0.002
Hispanic
Hispanic 13 1 (7.7) 2 (15.4) 3 (23.1) 16 0 (0.0) 0.37
Other 23 2 (8.7) 2 (8.7) 4 (17.4) 25 0 (0.0) 0.43

Insurance
Medicaid 264 39 (14.7) 81 (30.7) 120 (45.4) 285 45 (15.8) o 0.001
Private 427 11 (2.6) 34 (8.0) 45 (10.5) 478 20 (4.2) 0.02
Other 17 3 (17.6) 2 (11.8) 5 (29.4) 21 2 (9.5) 0.76
Percentages represent the fraction within each row with the specified characteristic. aComparison of detection rates between self-reported cigarette use and
high-level exposure by mass spectrometry.

© 2016 Nature America, Inc. Journal of Perinatology (2016), 1 – 5

 RETURN TO TABLE OF CONTENTS
Late pregnancy nicotine exposures
ES Hall et al
4
Table 3. Laboratory-based drug test results for 708 women comparing nicotine exposures subgroups
Characteristic Any drugs adjOR
(95% CI) N = 67
Maternal age (year) 1.10 (1.04–1.16)
Race
White, non-Hispanic (Reference)
Black, non-Hispanic 0.77 (0.37–1.59)
Hispanic 0.66 (0.06–7.08)
Insurance
Private (Reference)
Medicaid 3.52 (1.74–7.12)
Nicotine exposure
None (Reference)
Low-level 5.69 (2.09–15.46)
High-level 13.93 (7.06–27.49)
Abbreviations: adjOR, adjusted odds ratio; CI, confidence interval.
exposures during the last trimester of pregnancy for 16.5% of
women. Laboratory testing detected low-level exposures for an
additional 7.5% of mothers. Combined, 24.0% of the study
population had laboratory-detectable levels of nicotine exposure.
Further, we detected nicotine exposures in nearly half of
Medicaid-insured women (45.4%) compared with 15.8% who
self-reported cigarette use. These findings demonstrate the
inadequacy of current vital birth record measures for estimating
nicotine exposures during pregnancy and underscore the need for
improved measurement tactics that capture passive as well as
primary exposures to products other than just cigarettes.
Our findings have relevance given the recent rise in popularity
of electronic cigarettes, or e-cigarettes, which are perceived as a
safer alternative to traditional tobacco cigarettes.34 A critical
gap remains in the literature regarding the effects of e-cigarette
exposures on perinatal outcomes. Moreover, the current format
of vital birth statistics smoking measures is a critical barrier
for conducting population-level studies of e-cigarettes. We
adapted35,36 and developed several potential questions that could
be administered at the time of birth to further characterize
primary and secondary nicotine exposures beyond what is
currently measured by the Ohio birth certificate questionnaire
(Supplementary Appendix). Integration of laboratory test results
with vital records is another potential opportunity for calibrating
self-reported measures to better approximate the true prevalence
of various exposures.11
We found that women with positive nicotine exposures were
much more likely to test positive for other drug exposures; this
remained true even among women with low-level nicotine
exposures. Thus, accurate measurement of nicotine exposures is
critical to accurate identification and measurement of other drug
exposures and to inform optimal clinical management for exposed
newborns. This is becoming increasingly important as a con-
sequence of increased illicit opioid use over the past decade. By
2011, more than 1% of pregnant women used opioid-based pain
relievers or heroin illicitly,37 and by 2012, neonatal abstinence
syndrome affected 5.8 per 1000 newborns in the US.38
We noted a trend for differences among racial and ethnic
groups in nicotine detection comparing birth certificates to
laboratory tests. More than four times as many black, non-
Hispanic women had detectable nicotine exposures using
laboratory testing compared with self-report (7.9 vs 35.9%)
contrasted with a twofold increase among white, non-Hispanic
women (9.5 vs 21.5%). One explanation is that black, non-Hispanic
women may experience different types of nicotine exposures than
Journal of Perinatology (2016), 1 – 5
Cannabinoids adjOR Opioids adjOR Polypharmacy adjOR
(95% CI) N = 37 (95% CI) N = 27 (95% CI) N = 15
1.11 (1.03–1.19) 1.05 (0.97–1.14) 1.14 (1.03–1.26)
(Reference) (Reference) (Reference)
1.64 (0.70–3.88) 0.11 (0.01–0.81) 0.17 (0.02–1.40)
− 1.81 (0.19–16.99) −
(Reference) (Reference) (Reference)
2.35 (0.90–6.19) 3.92 (1.46–10.55) 2.74 (0.72–10.36)
(Reference) (Reference) (Reference)
14.54 (3.36–62.96) 0.97 (0.11–8.43) 8.79 (0.67–115.95)
38.69 (12.37–120.98) 4.04 (1.57–10.40) 28.73 (5.61–147.13)
white, non-Hispanic women, which are not captured by the birth
certificate worksheet. These include secondhand exposures or
exposures originating from nicotine products other than tobacco
cigarettes. If correct, this hypothesis, which we plan to test in a
future study, suggests that previously described underestimates of
nicotine exposures using birth certificate data may also contain a
disproportional racial bias.
There are several important limitations to the current study.
There were no significant differences detected between the
cohort of women who received laboratory testing and the larger
population of women who gave birth during the study suggesting
minimal bias in the subsample. However, no individual-level
nicotine exposure comparisons were made. Identifiable informa-
tion required for linkage between the two data sets was not
approved to protect the privacy of individuals from a perception
of intentional misreporting of smoking status. Though, as stated
previously, discrepancy between measured nicotine exposure
rates could only partially be attributed to any form of reporting
bias, intentional or not. Additional vital birth record survey
questions are needed to better evaluate exposure rates calculated
by the two measurement approaches which are not limited to
exposures from cigarette use alone. Finally, this analysis was
conducted using data from a single-center maternity hospital.
Future work will incorporate infant birth weight and gestational
ages, which were unavailable in the current analysis, to better
understand relationships between levels of nicotine exposure and
outcomes.
Our study identified a significantly elevated rate of women with
late pregnancy nicotine exposure using laboratory methods
compared with traditional self-report methods using birth
certificate worksheets. In addition, we identified a relationship
between high- and low-level nicotine exposures and other drug
exposures that also have an important role in mediating perinatal
outcomes. Thus, there remains a critical need for improved
measurement of nicotine exposures throughout pregnancy, which
capture primary as well as passive exposures from all potential
sources. We intend to expand our analysis to a regional scope and
include a prospective component to integrate and validate
additional survey questions to better enumerate sources of
nicotine exposure.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
© 2016 Nature America, Inc.
 RETURN TO TABLE OF CONTENTS
Late pregnancy nicotine exposures
ES Hall et al
ACKNOWLEDGEMENTS
This study includes data provided by the Ohio Department of Health, which should
not be considered an endorsement of the study or its conclusions. This work was
supported by the Cincinnati Children’s Hospital Perinatal Institute, Cradle Cincinnati,
and by a gift from Amgis Foundation Inc.
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minireview. Int Arch Occup Environ Health 1998; 71(3): 162–168.
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J Cancer Res Ther 2013; 9(1): 84–89.
30 Ohio Department of Health. Mother’s worksheet for child’s birth. 2014 [cited
February 18, 2016] Available from http://vitalsupport.odh.ohio.gov/gd/gd.aspx?
Page = 3&TopicRelationID = 306&Content = 5994.
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Journal of Perinatology (2016), 1 – 5
 RETURN TO TABLE OF CONTENTS
Original Research
Association of Reported Trimester-Specific
Smoking Cessation With Fetal
Growth Restriction
Kaitlin Blatt, BS, Elizabeth Moore, DO, Aimin Chen,
and Emily A. DeFranco, DO, MS
OBJECTIVE: To assess the association of reported smok-
ing cessation at various time points during pregnancy
with fetal growth restriction.
METHODS: This was a population-based retrospective
cohort study of singleton nonanomalous live births using
Ohio birth certificates, 2006–2012. Outcomes of women
who reported smoking only in the 3 months before con-
ception and women who reported smoking through the
first, second, or third trimester were compared with a ref-
erent group of nonsmokers. Multivariate logistic regres-
sion assessed the association between smoking cessation
at various times in pregnancy and fetal growth restriction
less than the 10th and 5th percentiles.
RESULTS: Of 927,424 births analyzed, 75% of mothers
did not smoke. Of smokers, 24% smoked preconception
only, 10% quit after the first trimester, 4% quit after the
From the Division of Maternal-Fetal Medicine, Department of Obstetrics and
Gynecology, and the Department of Environmental Health, University of Cincinnati
College of Medicine, and the Center for Prevention of Preterm Birth, Perinatal
Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio.
Presented at the American College of Obstetricians and Gynecologists Annual
Clinical and Scientific Meeting, May 2–6, 2015, San Francisco, California.
Ms. Blatt received research funding from an educational grant from the Univer-
sity of Cincinnati Department of Obstetrics and Gynecology Women’s Health
Scholars Program. Dr. DeFranco received research funding from the Perinatal
Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio,
March of Dimes Grant 22-FY14-470.
All of the analysis, interpretations, and conclusions that were derived from the
data source and included in this article are those of the authors and not the Ohio
Department of Health. Access to deidentified Ohio birth certificate data was
provided by the Ohio Department of Health.
Corresponding author: Emily A. DeFranco, DO, MS, Associate Professor,
Maternal-Fetal Medicine, University of Cincinnati College of Medicine,
Department of Obstetrics and Gynecology, 3255 Eden Avenue, Health
Professions Building, Room 154, Cincinnati, OH 45267-0526; e-mail:
emily.defranco@uc.edu.
Financial Disclosure
The authors did not report any potential conflicts of interest.
© 2015 by The American College of Obstetricians and Gynecologists. Published
by Wolters Kluwer Health, Inc. All rights reserved.
ISSN: 0029-7844/15
1452 VOL. 125, NO. 6, JUNE 2015
Copyright ª by The American College of Obstetricians
and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
MD, PhD, James Van Hook, MD,
second trimester, and 59% smoked throughout preg-
nancy. The rate of fetal growth restriction less than the
10th and 5th percentiles among nonsmokers was 8.1%
and 3.6%, respectively. Although smoking only in the
preconception period did not significantly increase fetal
growth restriction risk, smoking in any trimester did. The
adjusted odds ratio (95% confidence interval) for fetal
growth restriction less than the 10th and 5th percentiles,
respectively, of cessation after the first trimester was 1.19
(1.13–1.24) and 1.25 (1.17–1.33) and 1.67 (1.57–1.78) and
1.83 (1.68, 1.99) for cessation after the second trimester.
Women who reported smoking throughout pregnancy
had the highest risks of fetal growth restriction, 2.26
(2.22–2.31) and 2.44 (2.37–2.51), after accounting for the
influence of race, low socioeconomic status, and medical
comorbidities.
CONCLUSION: Smoking of any duration during preg-
nancy is associated with an increased risk of fetal growth
restriction with decreasing risk the earlier that cessation
occurs. Smoking cessation programs should focus on the
benefit of quitting as early in pregnancy as possible.
(Obstet Gynecol 2015;125:1452–9)
DOI: 10.1097/AOG.0000000000000679
LEVEL OF EVIDENCE: II
S
moking during pregnancy has been associated
with an increased risk of a multitude of adverse
outcomes, including fetal growth restriction.1,2 As of
2010, 23% of women nationwide smoked tobacco in
the 3 months before pregnancy, and just more than
half (54%) quit during pregnancy.3 In Ohio, a high-
prevalence smoking area, only 24% of women who
smoked in the 3 months before pregnancy quit before
conception and 16% of pregnant women continued to
smoke in the third trimester.3,4
Although several studies have examined the
effects of smoking cessation in pregnancy on fetal
growth restriction, many have been limited in size or
OBSTETRICS & GYNECOLOGY
 RETURN TO TABLE OF CONTENTS

ethnic diversity.5–8 Limited data exist to assess the
association between smoking cessation before preg-
nancy and in each trimester and risk of fetal growth
restriction. Additional knowledge about the benefits
of quitting in the preconception or early gestational
period would be an added incentive to quit earlier for
the women who struggle with this addiction. We
aimed to perform a large-scale population-based study
of recent U.S. births to quantify the influence of smok-
ing before pregnancy or in any trimester on the risk of
fetal growth restriction.
MATERIALS AND METHODS
The protocol for this study was approved by the
human subjects institutional review board of the Ohio
Department of Health and a deidentified data set was
provided for this analysis. This study was exempt
from review by the institutional review board at the
University of Cincinnati, Cincinnati, Ohio.
We performed a population-based retrospective
cohort study of all live births in Ohio over 7 years
(2006–2012) using vital statistics birth certificate re-
cords from the Ohio Department of Health. Women
were divided into one of five exposure groups based
on their reported smoking status: “nonsmokers,”
“smoked preconception only” (smoked in the 3
months preconception but not in any trimester),
“smoked through the first trimester” (smoked precon-
ception and the first trimester but not second or third
trimester), “smoked through the second trimester”
(smoked preconception and the first two trimesters
but not the third trimester), and “smoked throughout
pregnancy” (smoked before and in all three trimes-
ters). For each trimester, women who smoked an aver-
age of one or more cigarettes a day were considered
smokers. We also performed a sensitivity analysis
using a threshold of five cigarettes per day. We limited
analyses to singleton nonanomalous live births
between 20 and 42 weeks of gestation with available
data on smoking history.
The primary outcome was fetal growth restriction
less than the 10th and less than the 5th percentiles as
defined by the 1996 Alexander U.S. growth curves
reference.9 We compared baseline demographic,
socioeconomic, prenatal, and behavioral characteris-
tics among all five exposure groups. Additionally,
a linear regression was performed to assess the
dose–response relationship between cigarettes
smoked per trimester and birth weight.
Gestational age was defined by the best obstetric
estimate variable in the birth record, which combines
last menstrual period and ultrasound parameters.
Body mass index (BMI, calculated as weight (kg)/
[height (m)]2) was calculated using maternal precon-
ception height and weight, and gestational weight gain
was calculated by subtracting maternal weight at
delivery from preconception maternal weight.
Comparisons of dichotomous variables were
performed with x2 tests and continuous variables were
compared using analysis of variance. Multinomial
logistic regression estimated the adjusted odds ratio
(OR) of fetal growth restriction less than the 10th

Live births in Ohio, 2006–2012

(n=1,034,552)
Excluded (n=107,128)*
Gestational age <20 weeks: 689
Gestational age >42 weeks: 28,070
Missing gestational age: 2,261
Fetal anomalies or missing data:
40,805
Non-singleton gestations: 37,091
Study cohort
(n=927,424 )
Excluded (n=13,667)
Missing smoking data: 6,254
(0.67%)
Intermittent smoking patterns: 7,413
(0.80%)

Nonsmokers Smoked Smoked Smoked Smoked

(n=697,266; preconception through first through second throughout
75.2%) only trimester trimester pregnancy
(n=53,355; 5.8%) (n=21,803; 2.4%) (n=8,797; 1.0%) (n=132,536;
14.3%)

Fig. 1. Flow diagram of the study population. *Some births had more than one exclusion criterion.
Blatt. Smoking Cessation and Growth Restriction Risk. Obstet Gynecol 2015.

VOL. 125, NO. 6, JUNE 2015 Blatt et al Smoking Cessation and Growth Restriction Risk 1453

Copyright ª by The American College of Obstetricians

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Unauthorized reproduction of this article is prohibited.
 RETURN TO TABLE OF CONTENTS

and less than the 5th percentiles associated with vari-
ous smoking behaviors after adjusting for maternal
age, race, education level, marital status, pregestational
hypertension and diabetes, gestational hypertension
and diabetes, and BMI. Covariates were selected
based on differences noted in univariate comparisons
and those with biologic plausibility. Each smoking
group was compared with the referent group of non-
smokers. Additionally, a linear regression was per-
formed to assess the dose–response relationship
between cigarettes smoked per trimester and birth
weight.
Analyses were performed using STATA 12.1.
Results are reported as rates with associated P values

Table 1. Baseline Maternal Characteristics

Smoked Smoked
Preconception Smoked Through Smoked Through Throughout
Nonsmokers Only the 1st Trimester the 2nd Trimester Pregnancy
Factor (n5697,266) (n553,355) (n521,803) (n58,797) (n5132,536)

Demographic
Maternal race
Non-Hispanic white 517,166 (72.9) 44,435 (6.3) 17,728 (2.5) 7,130 (1.0) 114,230 (16.1)
Non-Hispanic black 120,430 (80.0) 6,534 (4.3) 3,123 (2.1) 1,355 (0.9) 14,920 (9.9)
Hispanic 36,657 (86.1) 1,858 (4.4) 753 (1.8) 249 (0.6) 2,564 (6.0)
Other 21,805 (93.4) 471 (2.0) 169 (0.7) 48 (0.2) 651 (2.8)
Parity 1 (0, 2) 0 (0, 1) 0 (0, 1) 1 (0, 2) 1 (0, 2)
Maternal age (y) 27.765.9 25.765.3 24.665.2 24.465.3 25.265.4
28 (23, 32) 25 (22, 29) 24 (21, 28) 23 (20, 27) 24 (21, 29)
Age group (y)
Younger than 20 63,110 (67.6) 6,163 (6.6) 3,580 (3.8) 1,524 (1.6) 16,883 (18.1)
20–34 538,815 (74.5) 43,783 (6.1) 17,068 (2.4) 6,777 (0.9) 106,755 (14.8)
35 or older 95,341 (86.3) 3,409 (3.1) 1,155 (1.1) 496 (0.5) 8,898 (8.1)
Socioeconomic
Less than high school 94,378 (13.5) 7,171 (13.4) 4,243 (19.5) 2,192 (24.9) 42,280 (31.9)
diploma
Unmarried 238,063 (34.1) 29,475 (55.2) 15,005 (68.8) 6,533 (74.3) 94,084 (71.0)
Women, Infants, and 239,827 (34.4) 26,265 (50.2) 13,141 (60.3) 5,709 (64.9) 90,035 (67.9)
Children enrollment
Medicaid 202,044 (29.0) 23,487 (44.0) 12,248 (56.2) 5,662 (64.4) 90,451 (68.3)
Prenatal care
Limited (5 or fewer visits) 49,531 (7.1) 3,293 (6.2) 1,700 (7.8) 976 (11.1) 16,423 (12.4)
Early initiation (12 wk of 400,724 (57.5) 32,033 (60.0) 11,185 (51.3) 4,054 (46.1) 61,947 (46.7)
gestation or less)
Late initiation (greater than 41,237 (5.9) 2,709 (5.1) 1,573 (7.2) 788 (9.0) 12,073 (9.1)
20 wk of gestation)
Maternal health indicators
Prior cesarean delivery 90,386 (13.0) 5,499 (10.3) 2,245 (10.3) 1,025 (11.7) 18,455 (13.9)
Underweight (prepregnancy 23,840 (3.4) 2,436 (4.6) 1,274 (5.8) 610 (6.9) 9,836 (7.4)
BMI [kg/m2] less than
18.5)
Obesity (prepregnancy BMI 153,533 (22.0) 12,356 (23.2) 5,197 (23.8) 2,101 (23.9) 30,293 (22.9)
30 or greater)
Gestational weight gain (lb) 31.2616.9 36.4618.8 36.5619.2 33.6619.5 30.3618.9
Chronic hypertension 13,123 (1.9) 980 (1.8) 374 (1.7) 196 (2.2) 2,232 (1.7)
Pregestational diabetes 5,412 (0.8) 402 (0.8) 196 (0.9) 83 (0.9) 1,188 (0.9)
Gestational hypertension or 32,252 (4.6) 2,754 (5.2) 1,075 (4.9) 373 (4.2) 4,407 (3.3)
preeclampsia
Gestational diabetes 37,789 (5.4) 3,076 (5.8) 1,228 (5.6) 483 (5.5) 6,370 (4.8)
BMI, body mass index.
Data are n (%), mean6standard deviation, or median (interquartile range).
Dichotomous variables are presented as percent of n for the corresponding smoking group, except for the categorical variables mother’s race
and age group, which reflect percentages across rows.
All comparisons are statistically significant at P#.001 for the x2 statistic corresponding to the five smoking group comparison for each
maternal characteristic in this table.

1454 Blatt et al Smoking Cessation and Growth Restriction Risk OBSTETRICS & GYNECOLOGY

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and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
 RETURN TO TABLE OF CONTENTS

and ORs with 95% confidence intervals (CIs). Com-
parisons were considered statistically significant if the
P value was ,.01 or the 95% CI did not include the
null value 1.0.
RESULTS
The total number of live births during the study period
was 1,034,552. After exclusions, there were 927,424
live births included in this analysis (Fig. 1). There
were minimal missing data (less than 2%) for most
variables analyzed; however, gestational age at the first
prenatal visit was missing in 25% and BMI and Med-
icaid status were missing in 5% and 4%, respectively.
There were few cases (n513,667 [1.5%]) with missing
smoking data or smoking behaviors that did not fall
within any of the five exposure groups. The reference
group of nonsmokers comprised 75.2% of births during
the study period. Nearly one in four women during the
study period smoked cigarettes. Of those, 23.8%
smoked preconception only, 9.7% smoked through
the first trimester, 3.9% smoked through the second
trimester, and the majority (59.2%) smoked throughout
the entire pregnancy (Fig. 1).
Seventy-six percent of the study population
comprised births to non-Hispanic white mothers
(n5709,297). Non-Hispanic white mothers were more
frequently smokers than nonwhite mothers
(n5188,985 [26.6%] compared with n534,628
[16.0%], P,.01) and more likely to smoke throughout
pregnancy (n5114,230 [16.1%] compared with
n518,135 [8.4%], P,.01). Young mothers aged youn-
ger than 20 years were more likely to be smokers than
women ages 20–34 years (n529,406 [31.5%] compared
with n5180,099 [24.9%], P,.01) and more likely to
smoke throughout pregnancy (n516,883 [18.1%] com-
pared with n5106,755 [14.8%], P,.01).
Women who reported quitting smoking in the
first trimester were more likely to initiate prenatal care
in the first trimester than women who reported
smoking throughout pregnancy (n532,033 [60.0%]
compared with n561,947 [46.7%], P,.01). Other
maternal characteristics associated with adverse smok-
ing behaviors included low education level, limited
prenatal care, late initiation of prenatal care at 20
weeks of gestation or greater, unmarried, Women,
Infants, and Children enrollment, and Medicaid
funded delivery (Table 1).
Women who reported smoking throughout preg-
nancy were more likely to be heavy smokers pre-
conception (more than 20 cigarettes per day) than
those who quit smoking early after the preconception
period (n576,149 [57.5%] compared with n516,595
[31.1%], P,.01; Table 2). However, women who
smoked throughout pregnancy reported a reduction
in their average cigarettes smoked per day from
17.169.9 preconception to 10.067.5 in the third tri-
mester (Table 2). In all groups who reported smoking
during pregnancy, women most frequently smoked
fewer than 10 cigarettes per day.
Birth outcomes associated with smoking through-
out pregnancy included preterm birth less than 37
weeks of gestation (n518,053 [13.6%] compared with
referent n569,794 [10.0%]), low birth weight less than
2,500 g (n515,052 [11.4%] compared with n539,173
[5.6%]), lower average birth weight (3,090 g compared
with 3,340 g), and neonatal intensive care unit

Table 2. Smoking Behavior Comparisons

Smoked Smoked
Preconception Smoked Through Smoked Through Throughout
Nonsmokers Only the 1st Trimester the 2nd Trimester Pregnancy
Smoking Behavior (n5697,266) (n553,355) (n521,803) (n58,797) (n5132,536)

Preconception
Average no. of cigarettes 0 11.869.6 14.6610.4 16.169.8 17.169.9
smoked/d
Heavy smoking (20/d or 0 16,595 (31.1) 9,617 (44.1) 4,644 (52.8) 76,149 (57.5)
more)
In final 3 mo of smoking
Average no. of cigarettes 0 11.869.7 9.068.1 7.267.2 10.067.5
smoked
Fewer than 10 0.0 20,897 (39.2) 11,806 (54.2) 5,832 (66.3) 56,815 (42.9)
10–19 0.0 15,863 (29.7) 5,901 (27.1) 1,956 (22.2) 49,540 (37.4)
20 or more 0.0 16,595 (31.1) 4,096 (18.8) 1,009 (11.5) 26,181 (19.8)
Data are n, %, or mean6standard deviation.
Dichotomous variables are presented as percent of n for the corresponding smoking group.
All comparisons are statistically significant at P#.001 for the x2 statistic corresponding to the five smoking group comparison for each
maternal characteristic in this table.

VOL. 125, NO. 6, JUNE 2015 Blatt et al Smoking Cessation and Growth Restriction Risk 1455

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 RETURN TO TABLE OF CONTENTS

admission (n58,298 [6.3%] compared with n534,300
[4.9%]; P,.01; Table 3). Absolute rates of other birth
outcomes were similar across the various smoking
groups, but P values were statistically significant,
likely as a result of the large sample size.
The overall frequency of fetal growth restriction
less than the 10th and 5th percentiles in the study
cohort was 9.8% (n590,613) and 4.6% (n542,547),
respectively. The rate of fetal growth restriction less
than the 10th and less than the 5th percentiles was
lowest in nonsmokers (8.1% [n556,666] and 3.6%
[n525,380]) followed by those who smoked precon-
ception only (8.4% [n54,485] and 3.8% [n52,034]).
For all groups who smoked in at least one trimester
of pregnancy, the risk of fetal growth restriction over
nonsmokers increased significantly. For women who
quit smoking in pregnancy, the adjusted OR (95%
CI) of smoking just through the first trimester was
1.19 (1.13–1.24) and 1.25 (1.17–1.33) and was higher
with smoking through the second trimester at 1.67
(1.57–1.78) and 1.83 (1.68–1.99), respectively for fetal
growth restriction less than the 10th and 5th percentiles
(Table 4). Smoking throughout pregnancy carried the
highest risk of fetal growth restriction, with a more than
twofold increased risk for birth weights less than the
10th and 5th percentiles, even after accounting for
coexistent influences of maternal age, race, education,
marital status, Medicaid-funded delivery, pregestation-
al hypertension and diabetes, gestational hypertension
and diabetes, and BMI (Fig. 2). The attributable risk of
smoking throughout pregnancy was 10.2% for fetal
growth restriction less than the 10th percentile and
5.8% for fetal growth restriction less than the 5th per-
centile (Table 4).
The dose–response analysis showed a significant
inverse linear correlation between the number of cig-
arettes smoked per day and birth weight. Each addi-
tional cigarette smoked per day in the first, second,
and third trimesters was associated with a decrease in
birth weight of 12.1, 14.8, and 14.5 g, respectively.
The results of a sensitivity analysis performed
after redefining smokers as those who reported five or
more cigarettes per day produced similar results.
Using this definition of smokers, the adjusted OR

Table 3. Birth Outcomes

Smoked
Smoked Smoked Through Smoked Through Throughout
Nonsmokers Preconception the 1st Trimester the 2nd Trimester Pregnancy
Outcome (n5697,266) Only (n553,355) (n521,803) (n58,797) (n5132,536)

Maternal
Vaginal delivery 456,531 (65.4) 33,739 (63.2) 14,007 (64.2) 5,536 (62.9) 87,168 (65.8)
Operative vaginal 39,144 (5.6) 3,392 (6.4) 1,367 (6.3) 471 (5.4) 6,668 (5.0)
delivery
Cesarean delivery 200,896 (28.8) 16,178 (30.3) 6,417 (29.4) 2,776 (31.6) 38,555 (29.1)
PROM 19,704 (2.8) 1,739 (3.3) 750 (3.4) 468 (5.3) 4,296 (3.2)
Preterm birth at less 69,794 (10.0) 5,096 (9.6) 2,477 (11.4) 1,590 (18.1) 18,053 (13.6)
than 37 wk of
gestation
Meconium 38,098 (5.5) 2,833 (5.3) 1,179 (5.4) 501 (5.7) 7,558 (5.7)
Induction of labor 220,696 (31.7) 19,660 (36.9) 7,977 (36.6) 2,971 (33.8) 41,281 (31.2)
Fetal intolerance to 44,932 (6.4) 4,022 (7.5) 1,516 (7.0) 688 (7.6) 7,899 (6.0)
labor
Neonatal
Birth weight (g) 3,340.06557.8 3,339.06557.0 3,280.06589.8 3,072.56762.9 3,090.16542.4
Low birth weight (less 39,173 (5.6) 3,035 (5.7) 1,585 (7.3) 1,306 (14.9) 15,052 (11.4)
than 2,500 g)
Extremely low birth 7,391 (1.1) 535 (1.0) 309 (1.4) 541 (6.2) 1,636 (1.2)
weight (less than
1,500 g)
NICU admission 34,300 (4.9) 2,720 (5.1) 1,260 (5.8) 930 (10.6) 8,298 (6.3)
Neonatal transfer 14,234 (2.0) 1,162 (2.2) 515 (2.4) 368 (4.2) 3,869 (2.9)
5-min Apgar score less 15,610 (2.2) 1,244 (2.3) 581 (2.7) 401 (4.6) 3,008 (2.3)
than 7
PROM, premature rupture of membranes; NICU, neonatal intensive care unit.
Data are n (%) or mean6standard deviation.
All comparisons are statistically significant at P#.001 for the x2 statistic corresponding to the five smoking group comparison for each
maternal characteristic in this table.

1456 Blatt et al Smoking Cessation and Growth Restriction Risk OBSTETRICS & GYNECOLOGY

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and Gynecologists. Published by Wolters Kluwer Health, Inc.
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 RETURN TO TABLE OF CONTENTS

Table 4. Rate of Fetal Growth Restriction in Singleton Pregnancies by Timing of Smoking Cessation

Smoked Smoked Smoked

Smoked Through the 1st Through the 2nd Throughout
Nonsmokers Preconception Trimester Trimester Pregnancy
Fetal Growth Restriction (n5697,266) Only (n553,355) (n521,803) (n58,797) (n5132,536)

Less than the 10th percentile 56,566 (8.1) 4,485 (8.4) 2,286 (10.5) 1,281 (14.6) 24,182 (18.3)
Attributable risk (95% CI) 0.3% (0.25–0.35) 2.4% (2.2–2.6) 6.5% (5.98–7.02) 10.2% (10.04–10.36)
Crude OR (95% CI) Reference 1.04 (1.01–1.07) 1.33 (1.27–1.39) 1.93 (1.82–2.05) 2.53 (2.49–2.57)
Adjusted OR* (95% CI) Reference 0.99 (0.95–1.02) 1.19 (1.13–1.24) 1.67 (1.57–1.78) 2.26 (2.22–2.31)
Less than the 5th percentile 25,380 (3.6) 2,034 (3.8) 1,105 (5.1) 649 (7.4) 12,500 (9.4)
Attributable risk (95% CI) 0.2% (0.16–0.24) 1.5% (1.34–1.66) 3.8% (3.4–4.2) 5.8% (5.67–5.93)
Crude OR (95% CI) Reference 1.05 (1.00–1.10) 1.41 (1.33–1.50) 2.11 (1.95–2.29) 2.76 (2.70–2.82)
Adjusted OR* (95% CI) Reference 1.00 (0.96–1.05) 1.25 (1.17–1.33) 1.83 (1.68–1.99) 2.44 (2.37–2.51)
OR, odds ratio; CI, confidence interval.
Data are n (%) unless otherwise specified.
All comparisons are statistically significant at P#.001 for the x2 statistic corresponding to the five smoking group comparison for each
maternal characteristic in this table.
* Odds ratios were adjusted for maternal age, race, education level, Medicaid, marital status, pregestational hypertension and diabetes,
gestational hypertension and diabetes, and body mass index. Births with fetal anomalies and multiple gestations were excluded.

(95% CI) of smoking just through the first trimester than the 10th and 5th percentiles), again similar to the
was 1.23 (1.16–1.30) and 1.28 (1.18–1.39) and was findings of the original analysis displayed in Table 4.
higher with smoking through the second trimester at
1.81 (1.67–1.97) and 1.96 (1.75–2.19) and third tri- DISCUSSION
mester at 2.38 (2.33–2.43) and 2.57 (2.50–2.65), Smoking during any trimester of pregnancy carries an
respectively, for fetal growth restriction less than the increased risk of fetal growth restriction over non-
10th and 5th percentiles. The risk of fetal growth smokers. Previous studies showed that women who
restriction was not increased with smoking only smoke during pregnancy have double the risk of fetal
before conception (adjusted OR 1.02 [0.98–1.06] growth restriction over women who do not smoke1
and 1.02 [0.97–1.05] for fetal growth restriction less and that roughly one fourth of all growth restriction

2.5

2.0
95% confidence intervals
Adjusted odds ratios and

1.5

Fig. 2. Odds of fetal growth

restriction in singleton pregnan-
cies by timing of smoking cessa- 1.0
tion. Odds ratios were adjusted
for maternal age, race, education
level, Medicaid, marital status, Fetal growth restriction <10% Fetal growth restriction <5%
0.8
pregestational hypertension and
diabetes, gestational hyperten-
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2015.

VOL. 125, NO. 6, JUNE 2015 Blatt et al Smoking Cessation and Growth Restriction Risk 1457

Copyright ª by The American College of Obstetricians

and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
 RETURN TO TABLE OF CONTENTS
cases can be attributed to smoking.10 Fetal growth
restriction is a serious pregnancy complication, carry-
ing a fivefold to 30-fold increase in neonatal mortality11
and an increased risk of preterm birth, necrotizing
enterocolitis, and respiratory distress syndrome.12
Recent evidence also suggests that fetal growth restric-
tion contributes to an increased risk of chronic adult
diseases such as noninsulin-dependent diabetes melli-
tus, hypertension, stroke, and coronary heart disease.13
In this large population-based cohort study, we found
that although preconception smoking was not associ-
ated with an increased risk of fetal growth restriction,
smoking during any trimester of pregnancy was asso-
ciated with fetal growth restriction risk.
Several studies have concluded that women who
quit smoking before the third trimester had similar
growth restriction outcomes as those who did not
smoke at all during pregnancy.6–8 However, these
findings of no significant risk increase in women
who smoked but quit earlier in pregnancy may have
been limited by smaller sample size (less than 11,200)
compared with our large cohort of nearly one million
singleton live births,5,6,8 In addition, few similar stud-
ies included a population of U.S. women, and the
findings of those born in other areas of the world
may not be applicable given regional and racial differ-
ences in birth weights and smoking patterns across the
world.7,8 Finally, one other large U.S. cohort study
concluded that quitting smoking in the first trimester
reduced risk of fetal growth restriction compared with
a referent group of women who smoked throughout
pregnancy.14 This study also drew the conclusion that
quitting smoking in the first trimester brought risk of
small for gestational age similar to that of nonsmokers,
but did not use nonsmokers as a referent group.14
Fetal growth is influenced by constitutional,
environmental, and genetic factors.15 The pharmaco-
genetics of maternal tobacco use and the effects of
smoking on fetal growth are complex. Because fetal
growth is continuous during pregnancy, early cessa-
tion plausibly results in less effect if the effect is from
genetic interaction or direct toxic effects of nicotine.16
Additionally, the effect of nicotine could theoretically
be the result of placental–smoking interaction. Decid-
ual invasion occurs during the first trimester. There-
fore, a critical window of exposure in the first
trimester may result in an early pregnancy-reversible
effect of smoking cessation followed by the remaining
gestational period in which smoking cessation can no
longer salvage normal placentation.17,18 Either or both
of these mechanisms could hypothetically explain the
greater influence earlier cessation has on normaliza-
tion of fetal growth as our study suggests. We are
1458 Blatt et al Smoking Cessation and Growth Restriction Risk
Copyright ª by The American College of Obstetricians
and Gynecologists. Published by Wolters Kluwer Health, Inc.
Unauthorized reproduction of this article is prohibited.
unaware of any previously published studies compar-
ing the risk of fetal growth restriction in women who
quit smoking preconception and in each trimester
with a referent group of nonsmokers.
There are a number of limitations to a study using
vital statistics data for research. Some data variables
including maternal demographic information and
gestational age at birth appear to be very reliably
recorded in the birth certificate.19 However, data on
pregnancy complications and medical comorbid con-
ditions are underreported, which may limit the ability
to thoroughly adjust for confounding risk factors for
fetal growth restriction.20 Additionally, smoking may
be underreported on birth certificate data when com-
pared with anonymous Pregnancy Risk Assessment
Monitoring System surveys, potentially making the
effect of smoking even stronger than reported here.21
However, self-reported smoking has been shown to be
a valid measure of reproductive smoking behavior,
especially when timing of smoking exposure is criti-
cal.22 Information regarding alcohol intake, drug use,
and secondhand smoke exposure was not available in
the data set used for this analysis and thus could not
be accounted for as potentially confounding factors.
Our study reinforces prior conclusions that the
strongest association between smoking and fetal growth
restriction occurs in the third trimester. Additionally,
this study provides novel information of an increased
risk of fetal growth restriction with smoking in any
trimester of pregnancy with decreasing risk the earlier
smoking cessation occurs. Early initiation of prenatal
care may assist women in making the decision to quit
smoking early in pregnancy. The only way to achieve
the same risk of fetal growth restriction as nonsmoking
mothers is by quitting before conception, although
quitting at any point is beneficial. Therefore, smoking
cessation programs should focus on the benefit of
quitting in the preconception period or as early in
pregnancy as possible.
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5. England LJ, Kendrick JS, Wilson HG, Merritt RK,
Gargiullo PM, Zahniser SC. Effects of smoking reduction dur-
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Yamagata Z. Effect of maternal smoking cessation before and
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9. Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan M. A
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Brabin BJ. Population attributable risk for adverse pregnancy
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11. Peleg D, Kennedy CM, Hunter SK. Intrauterine growth restric-
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Morbidity and mortality among very-low-birth-weight neonates
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restriction. Semin Perinatol 2008;32:213–8.
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14. Polakowski LL, Akinbami LJ, Mendola P. Prenatal smoking
cessation and the risk of delivering preterm and small-for-
gestational-age newborns. Obstet Gynecol 2009;114:318–25.
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Norris FD, Tashiro M. Fetal growth and perinatal viability in
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Nadisauskiene R, Nieuwenhuijsen MJ. Low level maternal
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Childbirth 2012;12:161.
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Sergent F, et al. Characterization of the adverse effects of nico-
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19. Dietz PM, Bombard JM, Hutchings YL, Gauthier JP,
Gambatese MA, Ko JY, et al. Validation of obstetric estimate
of gestational age on US birth certificates. Am J Obstet Gynecol
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20. Reichman NE, Schwartz-Soicher O. Accuracy of birth certifi-
cate data by risk factors and outcomes: analysis of data from
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21. Tong VT, Dietz PM, Farr SL, D’Angelo DV, England LJ.
Estimates of smoking before and during pregnancy, and smok-
ing cessation during pregnancy: comparing two population-
based data sources. Public Health Rep 2013;128:179–88.
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Self-reported smoking, cotinine levels, and patterns of smoking
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Smoking Cessation and Growth Restriction Risk 1459
 RETURN TO TABLE OF CONTENTS

American Journal of Obstetrics and Gynecology (2005) 192, 1856–63

www.ajog.org

Smoking in pregnancy revisited: Findings from a large

population-based study
Ahmad O. Hammoud, MD,a Emmanuel Bujold, MD,a Yoram Sorokin, MD,a
Christiane Schild, MD,b Martin Krapp, MD,b Peter Baumann, MDa,*

Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI,a and Department of Obstetrics and
Gynecology, Medical University Lübeck, Lübeck, Germanyb

KEY WORDS Objective: The purpose of this study was to characterize the effect of smoking on the incidence of
Smoking various pregnancy complications.
Pregnancy Study design: A population-based retrospective analysis with a perinatal database of 170,254
Complications singleton pregnancies was performed. The rate of pregnancy complications was calculated in
Preeclampsia 4 strata of smokers: Nonsmokers, 1 to 5 cigarettes per day, 6 to 10 cigarettes per day, and O10
Intrauterine growth cigarettes per day. Logistic regression was used to calculate odds ratios as measures of an
restriction association of smoking with various pregnancy complications after correction for confounding
Preterm delivery factors.
Results: The mean age of the study population was 29 G 4.8 years. The odds ratio for
preeclampsia was 0.64 (95 % CI, 0.59-0.70), for intrauterine growth restriction was 2.4 (95% CI,
2.34-2.53), and for preterm delivery was 1.2 (95% CI, 1.13-1.28).
Conclusion: Smoking decreased the incidence of preeclampsia in a dose-effect manner and was
shown to increase the rate of intrauterine growth restriction and preterm delivery.
Ó 2005 Elsevier Inc. All rights reserved.

Smoking is among the most preventable causes of
female morbidity and death in the United States.1 An
estimated 27.2% of reproductive aged women smoke
cigarettes; this is equivalent to O14 million women of
ages 18 to 44 years who are smokers. During pregnancy,
the rate of smoking ranges from 15% to 30%1; adverse
Presented at the 71st Annual Meeting of the Central Association of
Obstetricians and Gynecologists, October 13-16, 2004, Washington,
DC.
* Reprint requests: Peter Baumann, MD, Department of Obstetrics
and Gynecology, Hutzel Women’s Hospital, Wayne State University,
4707 St. Antoine Blvd, Detroit, MI 48201.
E-mail: Pbaumann@med.wayne.edu
outcomes in the context of smoking affect not only the
mother but also the fetus and newborn infant as well.1
Smoking has been shown to increase the rate of preterm
delivery and to reduce birth weight.2,3 Although it has
been unexplained to date, smoking has also been shown
to reduce the incidence of hypertensive disorder of
pregnancy.4
Many of the previous studies focused on individual
aspects of the effect of smoking on pregnancy compli-
cations and fetal outcome.2,3 Drawing on a statewide
perinatal database the purpose of this study was to
investigate the relationship of smoking, preeclampsia,
intrauterine growth restriction (IUGR), preterm labor,
placental abruption, and other pregnancy complications

0002-9378/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.ajog.2004.12.057
 RETURN TO TABLE OF CONTENTS
Hammoud et al
in a large population-based study after correction for
potential confounding factors.
Material and methods
This study analyzed a perinatal database that was col-
lected from the state of Schleswig-Holstein, Germany,
that was designed to improve the quality of obstetric
care. From 1991 until 1997, 29 delivery units in the state
participated in the data collection. For the purpose of
this analysis, we included all 170,254 singleton pregnan-
cies that delivered during this period. This database was
described in a previous publication.5 Briefly, the data
collection sheet is a single-page sheet that is divided into
5 sections that match sections in an elaborate passport-
type version of what is known in the United States as the
prenatal care card. At the time of delivery, this sheet is
filled out by a resident who transfers the information
that is collected throughout the pregnancy from the
prenatal care card and adds information that is obtained
by interviewing the expectant mother at the time of
delivery. Data collection pertains to the following areas:
(1) maternal sociodemographic characteristics; (2) the
course of the pregnancy, including coded entry of as
many as 9 of 52 recognized risk factors that include
2 open-ended items (‘‘other’’); (3) delivery data that
include coded entry of as many as 6 birth risks and as
many as 5 indications for operative delivery of a total of
34 items; (4) the condition of the neonate; and (5) the
postpartum maternal condition. The smoking status and
the number of cigarettes smoked per day were obtained
at the time of delivery.
The maternal sociodemographic section included the
following variables: self-assessed number of cigarettes
smoked per day during pregnancy, age, prepregnancy
weight, height, number of prenatal visits, and maternal
perception of exposure to social and psychologic stress.
Smoking was classified into 4 categories potentially to
demonstrate a dose-effect relationship: nonsmoker, 1 to
5 cigarettes per day, 6 to 10 cigarettes per day, and O10
cigarettes per day. For binary logistic regression pur-
poses, we recoded smoking as a binary variable.
Variables ‘‘smoking’’ and ‘‘preeclampsia’’ were sub-
jected to cross-table analysis separately for primiparous
and for multiparous women to determine any degree of
association with any of the 50 risk factors, excluding
‘‘other.’’ Risk factors that were identified as being
associated with these variables were entered into a logis-
tic regression model to account for interactions between
the risk factors.
Pregnancy outcome was determined by the calcula-
tion of the rates of the most common pregnancy
complications, which included preeclampsia (defined as
blood pressure R140/90 mm Hg that was associated
with proteinuria [defined as proteinuria R100 mg/dL
1857
(2C on urine dipstick)]) or the presence of seizures,
preterm delivery (defined as delivery at !37 weeks of
gestation), placental abruption, placenta previa, cesar-
ean delivery, pre-existing and gestational diabetes melli-
tus, and cord prolapse.
Neonatal outcome was evaluated by the calculation
of the rate of IUGR (defined as birth weight %10th
percentile for the respective gestational age) and the
rates of meconium-stained amniotic fluid, clinical as-
phyxia (eg, pale skin, lack of breathing efforts, heart rate
!100 beats/min), depressed Apgar scores (defined as
scores !7 at 5 or 10 minutes of age), the need for
intubation, transfer to pediatric service, intrauterine
death, or neonatal death during the first week of life.
The incidences of pregnancy complications and fetal
outcomes were calculated for each of the smoking
categories. Chi-squared for trend statistics was used to
test for significance of differences between the incidences
of maternal and fetal complications in the different
smoking categories. Binary logistic regression was used
to calculate odds ratios as measures of association of
smoking with preeclampsia, preterm delivery, IUGR,
placental abruption, placenta previa, and neonatal in-
tubation after correction for potential confounding
factors. To determine the effect of each smoking
category on preeclampsia, multinomial logistic regres-
sion was used. SPSS statistical software (version 10.0;
SPSS Inc, Chicago, Ill) was used for analyses.
Results
Of the 170,254 singleton gestations, 157,857 had the
history of smoking available and subsequently were
included; 36,705 smokers (23%) were identified. The
mean age of the population was 29 G 4.8 years.
Sociodemographic data and possible confounding fac-
tors in the different smoking groups are presented in
Table I. Mothers of advanced age (maternal age O35
years) in all of the intensity categories smoked signifi-
cantly less than women below that age, although women
at the opposite extreme of reproductive age (aged !18
years) smoked significantly more. Multiparous women
were more frequently ‘‘heavier’’ smokers than primipa-
rous women. Mothers who smoked sought prenatal care
less often. The rate of prenatal visits of %4 was higher in
heavy smokers (15.2%) compared with nonsmokers
(12.7%).
In the overall patient population, the rate of pre-
eclampsia was correlated inversely to the number of
cigarettes smoked per day (Table II). A logistic re-
gression model showed an odds ratio of 0.64 (95 % CI,
0.59-0.70) for preeclampsia in patients who smoked
after correcting for all factors that were associated with
smoking and/or preeclampsia in the cross-table analysis
that included social and psychologic stress, age !18
 RETURN TO TABLE OF CONTENTS

1858 Hammoud et al

Table I Demographic and social characteristics of women, categorized by intensity of smoking

Nonsmoker 1-5 Cigarettes/d 6-10 Cigarettes/d O10 Cigarettes/d
Variable (n = 121,152) (n = 10,022) (n = 13,631) (n = 13,052) P value*
Mean maternal age (y) 29.34 28.17 27.78 27.9 ! .001
Maternal age R35 y (%) 13.0 9.8 9.1 11.1 ! .001
Maternal age %18 y (%) 0.4 0.6 0.7 0.5 ! .001
Gestational age at 39.21 39.18 39.10 38.9 ! .001
delivery (wk)
Nulliparity (%) 42.2 43.0 36.8 29.9 ! .001
Social or psychologic 2.4 3.1 3.9 6.0 ! .001
stress (%)y
Social or psychologic 0.6 0.7 1.0 1.4 ! .001
stress (%)z
Prenatal visits %4 (%) 12.7 14.4 15.0 15.2 ! .001
Body mass index O30 7.9 8.7 10.6 12.3 ! .001
kg/m2 (%)
* c2 for trend test; a probability value of !.05 was considered statistically significant.
y
At the beginning of the pregnancy.
z
Arising during pregnancy.

Table II Pregnancy-related outcomes in women, categorized according to intensity of smoking

Nonsmoker 1-5 Cigarettes/d 6-10 Cigarettes/d O10 Cigarettes/d
Outcome (%) (n = 121,152) (n = 10,022) (n = 13,631) (n = 13,052) P value*
Preeclampsia 2.5 2.0 1.9 1.9 ! .001
Preterm delivery 6.1 6.9 7.3 8.9 ! .001
Preterm premature rupture 2.4 2.8 2.7 11.4 ! .001
of membranes
Placenta previa 0.3 0.3 0.3 0.4 .09
Placental abruption 0.5 0.6 0.7 0.8 ! .001
Hemorrhage after 28 weeks 0.9 0.9 1.0 1.3 ! .001
Thromboembolism 0.1 0.1 0.1 0 .23
Pre-existing diabetes mellitus 0.2 0.2 0.2 0.2 .20
Gestational diabetes mellitus 0.4 0.3 0.3 0.4 .20
Cord prolapse 0.1 0.1 0.1 0.2 .02
Cesarean delivery 16.2 16.7 16.6 16.0 .27
* c2 for trend test; a probability value of !.05 was considered statistically significant.

years, age R35 years, body mass index O30 kg/m2,
previous termination of pregnancy, preterm labor, pre-
existing diabetes mellitus, gestational diabetes mellitus,
parity, and infertility treatment. We also found that an
increase in smoking of 5 cigarettes per day is associated
with an 18% decrease in the incidence of preeclampsia.
Stratified by gestational age at delivery, the rate of
preeclampsia in smokers compared with nonsmokers
increased with advancing gestational age. Even though
statistically not significant, beyond 40 weeks, the rate of
preeclampsia in smokers exceeded the rate in non-
smokers (ie, the incidence of preeclampsia in smokers
was 2.2% compared with 1.6% in nonsmokers; P = .19;
Figure 1).
Smoking increased the risks of preterm delivery and
preterm premature rupture of membranes, both of
which were related directly to the number of cigarettes
smoked per day, as shown in Table II. Logistic re-
gression revealed an odds ratio for preterm delivery of
1.2 (95% CI, 1.13-1.28) and for preterm premature
rupture of membranes of 1.3 (95% CI, 1.12- 1.40) after
correction for IUGR, body mass index O30 kg/m2,
parity, placenta previa, placental abruption, and pre-
eclampsia (Figure 2).
Mode of delivery and thromboembolic complications
were not correlated with maternal smoking. The in-
cidence of placentation disturbances that were exempli-
fied by placental abruption was higher in smokers
compared with nonsmokers, with an increased incidence
correlated to heavier maternal smoking (Table II).The
incidence of placenta previa was not affected by the
smoking status of the mother (Table II).
Neonatal outcome was altered significantly in re-
lation to maternal smoking. The incidence of IUGR
 RETURN TO TABLE OF CONTENTS

Hammoud et al 1859

Figure 2 Odds ratios of pregnancy complications that were

Figure 1 Rate of preeclampsia in cohorts of smoking and
related to smoking.
nonsmoking women who were delivered at various gestational
ages.

Table III Neonatal outcome in women, categorized according to intensity of smoking

Nonsmoker 1-5 Cigarettes/d 6-10 Cigarettes/d O10 Cigarettes/d
Outcome (%) (n = 121,152) (n = 10,022) (n = 13,631) (n = 13,052) P value*
IUGR 5.7 9.4 12.3 15.8 ! .001
Neonatal clinical asphyxia 1.5 1.4 1.8 1.8 ! .001
5-Min Apgar score !7 5.5 5.6 5.8 6.5 ! .001
10-Min Apgar score !7 1.8 1.6 2.0 2.2 ! .001
Need for neonatal intubation 1.0 1.0 1.0 1.3 ! .001
Transfer to pediatric care 9.1 10.3 10.9 12.7 ! .001
Meconium-stained fluid 8.5 9.9 9.6 10.1 ! .001
Intrauterine fetal death 0.3 0.3 0.2 0.4 .16y
Neonatal death during the 0.2 0.1 0.1 0.2 .56
first week of life
* c2 for trend test; a probability value of !.05 was considered statistically significant.
y
The rate of intrauterine fetal death remained not significantly different, even if heavy smokers (O10 cigarette per day) were compared with
nonsmokers (P = .19).

increased steadily from 5.7 % in nonsmokers to 15.8 %
in patients who smoked O10 cigarettes per day (Table
III). The mean birth weight of neonates of mothers who
smoked was lower than those whose mothers did not
smoke, regardless of gestational age (Figure 3). The
neonatal weight correlated negatively with the number
of cigarettes smoked per day. In a logistic regression
analysis, we found reductions in birth weight of
111 g,

175 g, and
236 g for women smoked 1 to 5, 6 to 10,
and O10 cigarettes per day, respectively.
Rates of meconium-stained amniotic fluid were
correlated directly to maternal smoking. The neonatal
status at delivery that was expressed by Apgar scores
showed that newborn infants with smoking mothers had
higher rates of depressed Apgar scores both at 5 and 10
minutes of age. Rates of clinical asphyxia and the need
for neonatal intubation were significantly higher in
offspring of mothers who smoked O10 cigarettes per
day, compared with nonsmokers, as was the rate of
transfer to pediatric services. In our study, intrauterine
fetal death or neonatal death during the first week of life
was not affected by the smoking habits of the mothers
(Table III).
The incidence of IUGR in relation to smoking and
preeclampsia is given in Table IV. In patients who
smoked and had no preeclampsia, the incidence of
IUGR was 12.6%; in patients who had preeclampsia
and did not smoke, the incidence of IUGR was 17.6%;
and in patients who both smoked and had preeclampsia,
the incidence of IUGR was 20.8%.
Comment
Analysis of our database of 170,254 singleton pregnancy
outcomes that covered 87.5% of all singleton deliveries
in the state of Schleswig-Holstein, Germany, indicates
that, during the time period observed, smoking signif-
icantly altered many pregnancy outcomes. Smoking had
detrimental effects on pregnant women and their fetuses,
 RETURN TO TABLE OF CONTENTS

1860 Hammoud et al

Figure 3 Mean birth weight according to gestational age and smoking status.

except for its ‘‘beneficial’’ effect on the rate of pre-

Table IV Risk of IUGR in women with and without pre-
eclampsia. The risk reduction for preeclampsia of eclampsia who smoke cigarettes
cigarette smoking has been addressed by a number of
authors.6-9 Some of their focus has been on the temporal Risk of IUGR:
Smoking (%)
relationship between smoking, smoking cessation, and
the manifestation of preeclampsia.6 A comprehensive Preeclampsia No Yes Odds ratio 95% CI
review of the relationship between smoking and pre- No 5.4 12.6 2.5 2.44-2.64
eclampsia showed that smoking is associated with a Yes 17.6 20.8 1.3 1.00-1.50
32% reduction in the risk of preeclampsia with dose-
effect characteristics.4 A study by Zhang et al7 confirmed
that smoking reduces the risk of hypertension during had quit smoking during pregnancy (20.4%) and to
pregnancy; this protective effect appeared to continue patients who had never smoked (26.4%).6
even after smoking cessation. The results of our study seem to support the notion
When Lain et al9 attempted to quantify smoking that smoking not only is associated with a reduction of
using urinary cotinine concentration, they were able to the risk to develop preeclampsia but also that this
demonstrate a reduction in the risk of preeclampsia in reduction seems to be directly proportional to the
relation to cotinine concentrations. Data from the number of cigarettes smoked per day. However, when
Calcium for Preeclampsia Prevention trial showed that we stratified the rate of preeclampsia by gestational age,
the incidence of gestational hypertension and pre- the apparent protective effect of smoking disappeared
eclampsia was lower in patients who continued smoking with advancing gestational age, indeed, O40 weeks of
during pregnancy (17.9%) compared with patients who gestation the rate of preeclampsia in smokers surpassed
 RETURN TO TABLE OF CONTENTS
Hammoud et al
the rate in nonsmokers. This finding is novel and to our
knowledge has not been described in any previous
report. We hypothesize that this phenomenon, at least
in part, is explained by the fact that placental damage
from smoking leads to severe complications that result
in preterm delivery that outpaces the clinical manifesta-
tion of preeclampsia.
Different mechanisms have been proposed to explain
the association between smoking and the decreased
risk of preeclampsia, which include the inhibition of
thromboxane A2, the stimulation of nitric oxide, or the
suppression of the immune system.8 Levels of soluble
adhesion molecules intercellular adhesion molecule–1,
vascular cell adhesion molecule–1, and E-selectin con-
centrations that were derived from endothelium (a
putative location of paracrine blood pressure regulation)
were shown to be elevated in pregnancies that were
complicated by preeclampsia.10 In a recent study, the
concentration of these markers (cellular fibronectin,
vascular cell adhesion molecule–1, and intercellular ad-
hesion molecule–1) were shown to be altered in patients
with preeclampsia who smoke. Smokers had overall
lower concentration of cellular fibronectin. Smokers
had lower concentrations of vascular cell adhesion
molecule–1 as well, but the difference was not statisti-
cally significant.8
Our findings regarding the relationship between
smoking and an increased rate of preterm delivery are
not supported unanimously in the literature. Some
studies, usually those studies that looked at much
smaller numbers than ours, have found no significant
association between smoking and preterm birth.11 Sup-
porting our findings is the recent study by Peacock
et al,12 who found an association between smoking and
very early birth (!32 weeks of gestation). In another
study, women with previous term delivery who smoked
during a subsequent pregnancy had increased rates of
very and moderately preterm deliveries in the second
pregnancy.13
Interpretations of the relationship between smoking
and preterm birth also have drawn on chemophysiologic
approaches that include a potential effect of smoking
on collagen production or an inhibitory effect on the
secretion of the enzyme platelet-activating factor acetyl-
hydrolase and the subsequent production of platelet-
activating factor and prostaglandin E2 that produce
myometrial contractions.3
In our mathematic model to predict placental abrup-
tion, smoking was a contributing factor.5 A large meta-
analysis that looked into the relationship between
smoking and placental abruption showed that smoking
was associated with a 90% increased risk of placental
abruption.14 The same study showed a dose-effect
relationship between smoking and placental abruption.
Furthermore, in the presence of smoking, the risk of
abruption was further increased because of hypertensive
1861
disorders of pregnancy.5,14 The relationship between
smoking and placental abruption is not understood
clearly. There is some evidence of placental changes
that are associated with smoking (such as a greater
incidence of nuclear clumps in the perivillous syncytio-
trophoblast) increased capillary fragility and alterations
in the uteroplacental blood flow.15 Moreover, the
placentas of smokers were found to be enlarged and
contained lesions that were characteristic of under
perfusion of the uterus.14 In smokers, the volume,
surface area, and the calculated lengths for the villous
capillaries were reduced significantly compared with an
increase of the trophoblast volume.16
Maternal cigarette smoking is an established contrib-
utor to a reduction in neonatal size. The mean birth
weight of infants of women who smoked during
pregnancy was found to be 170 to 200 g less than that
of infants of nonsmokers.1 In a logistic regression
analysis, we found reductions in birth weight of
111 g,

175 g, and
236 g for women who smoked 1 to 5, 6 to
10, and O10 cigarettes per day, respectively. In a recent
study that examined fetal growth in smokers, Bernstein
et al2 demonstrated that neonatal weight was reduced
among smokers (3269 G 507 g in smokers compared with
3519 G 411 g in nonsmokers; P ! .01). Smoking did not
affect the growth rate of head circumference or femur
length. Growth rates of abdominal circumference were
slower in smokers compared with nonsmokers. The
muscle area was reduced significantly among smokers.
There was a reduction in the rate of fat deposition in the
thighs of fetuses of smoking mothers. This study showed
that smoking appears to have a selective effect within lean
body mass compartments; the affected compartments
include peripheral fetal muscle.
Smoking is one of the most important preventable
risk factors for pregnancy complication. Cnattingius
et al13 showed that smoking cessation can reduce the
risk of an iatrogenic preterm delivery in a high-risk
patient population. They showed that, in women with
a history of preterm delivery and smoking, those women
who did not smoke during or after pregnancy were less
likely to have a very or moderately preterm second
delivery. Other studies demonstrated that low birth
weight could be reduced by 17% to 26% by stopping
smoking during pregnancy. A concrete smoking cessa-
tion plan, coupled with the use of nicotine replacement
when indicated, and proper follow-up care has been
shown to help women quit smoking and avoid relapse.17
References
1. American College of Obstetricians and Gynecologists. Smoking
and women’s health. Washington (DC): The College; 1997.
Educational bulletin no.: 240.
2. Bernstein IM, Plociennik K, Stahle S, Badger GJ, Secker-Walker
R. Impact of maternal cigarette smoking on fetal growth and body
composition. Am J Obstet Gynecol 2000;183:883-6.
 RETURN TO TABLE OF CONTENTS
1862
3. Kyrklund-Blomberg N, Cnattingius S. Preterm birth and maternal
smoking: risks related to gestational age and onset of delivery. Am
J Obstet Gynecol 1998;179:1051-5.
4. Conde-Agudelo A, Althabe F, Belizán JM, Kafury-Goeta AC.
Cigarette smoking during pregnancy and risk of preeclampsia:
a systematic review. Am J Obstet Gynecol 1999;181:1026-35.
5. Baumann P, Blackwell SC, Schild C, Berry SM, Friedrich HJ.
Mathematic modeling to predict abruptio placentae. Am J Obstet
Gynecol 2000;183:815-22.
6. England LJ, Levine RJ, Qian C, Morris CD, Sibai BM, Catalano
PM, et al. Smoking before pregnancy and risk of gestational
hypertension and preeclampsia. Am J Obstet Gynecol
2002;186:1035-40.
7. Zhang J, Klebanoff MA, Levine RJ, Puri M, Moyer P. The
puzzling association between smoking and hypertension during
pregnancy. Am J Obstet Gynecol 1999;181:1407-13.
8. Lain KY, Wilson JW, Crombleholme WR, Ness RB, Roberts JM.
Smoking during pregnancy is associated with alterations in markers
of endothelial function. Am J Obstet Gynecol 2003;189:96-1201.
9. Lain KY, Powers RW, Krohn MA, Ness RB, Crombleholme WR,
Roberts JM. Urinary cotinine concentration confirms the reduced
risk of preeclampsia with tobacco exposure. Am J Obstet Gynecol
1999;181:1192-6.
10. Austgulen R, Lien E, Vince G, Redman CW. Increased maternal
plasma levels of soluble adhesion molecules (ICAM-1, VCAM-1,
E-selectin) in preeclampsia. Eur J Obstet Gynecol Reprod Biol
1997;71:53-8.
11. Savitz DA, Dole N, Terry JW, Zhou H, Throp JM. Smoking and
pregnancy outcome among African-American and white women in
central North Carolina. Epidemiology 2001;12:636-42.
12. Peacock JL, Bland JM, Anderson R. Preterm delivery: effects of
socioeconomic factors, psychological stress, smoking, alcohol, and
caffeine. BMJ 1995;311:531-5.
13. Cnattingius S, Granath F, Petersson G, Harlow BL. The influence
of gestational age and smoking habits on the risk of subsequent
preterm deliveries. N Engl J Med 1999;341:943-8.
14. Ananth CV, Smulian JC, Vintzileos AM. Incidence of placental
abruption in relation to cigarette smoking and hypertensive
disorders during pregnancy: a metanalysis of observational studies.
Obstet Gynecol 1999;93:622-8.
15. Salafia C, Shiverick K. Cigarette smoking and pregnancy: II,
vascular effects. Placenta 1999;20:273-9.
16. Larsen LG, Clausen HV, Jonsson L. Stereologic examination of
placentas from mothers who smoke during pregnancy. Am J
Obstet Gynecol 2002;186:531-7.
17. American College of Obstetricians and Gynecologists. Smoking
cessation during pregnancy. Washington (DC): The College; 2000.
Educational bulletin no.: 260.
Discussion
DR ROBERT MITTENDORF, Chicago, Illinois. I want to
congratulate you for your analyses from such a large,
European data set. Such collaborations, and their
execution, usually provide us with some challenges.
Concerning the manuscript, in brief, I will talk about
the previous evidence that validated the data, any
inferences that can be made from the current data set,
and then ask Dr Hammoud about practical applications
for the future that will be based on this work.
First of all, the profound effect of smoking in regard
to IUGR is well established. However, the paradoxic
relationship between a possible protective effect for
Hammoud et al
smoking in regard to preeclampsia, in the past, was
suspect. Such a notion did seem to be the world turned
on its head because smoking has been shown to be
deleterious to many human organ systems. Why should
it be protective in a disease like preeclampsia?
Much to our delight and surprise, in 1999, Lain et al
at the University of Pittsburgh, using biologic data,
established beyond a reasonable doubt that smoking
was protective in the instance of preeclampsia. She used
levels of urinary cotinine as a biologic marker (cotinine
is the primary metabolite of nicotine).
Lain showed that women who had preeclampsia had
lower levels of cotinine in their urine than did control
subjects without preeclampsia. As it turned out, only
22% of mothers with preeclampsia had detectable
urinary cotinine levels, whereas 48% of control subjects
had been exposed to smoking and were excreting
detectable levels of urinary cotinine. The 70% reduction
in the risk of preeclampsia was significant.
With that in mind, let us accept the likelihood that
the finding of Hammoud et al, in regard to both
smoking and fetal growth restriction and smoking and
pre-eclampsia, are valid and not merely unsubstantiated
epidemiologic findings.
Concerning practical applications, in Table IV, there is
an interesting result. Please note that in the cell in which
the mother neither smoked nor got preeclampsia, the
prevalence of growth restriction is only 5.4%, when the
expected value would by definition be 10%. Thus, we may
reason that, when one of our patients without preeclamp-
sia is carrying a growth-restricted fetus, there is a sub-
stantial probability that the mother is a smoker or is
exposed to passive smoking.
Based on these important findings, I now
Dr Hammoud to share his thoughts and opinions. First,
how can we better determine whether our patients are
smoking? Second, if our patients are smoking, what can
we do to assist them in becoming abstemious? Lastly, in
your opinion, is it conceivable that your future research
or that of others will find a component or components in
cigarette smoke that could be used, in a practical way,
for the prevention of preeclampsia?
DR HAMMOUD (Closing). More than 22 million women
in the United States continue to smoke cigarettes. From
1965 to 1990, smoking declined by 40%, but since 1990,
the prevalence stagnated. Remarkably, there is an
increase in smoking among high school students; the
prevalence of smoking in this group increased from 27%
in 1991 to 35% in 1995. Habits formed at an early age
are more difficult to abandon, even when health circum-
stances (ie, pregnancy) make this highly desirable not
just for the smoking woman but even more so for her
fetus. Consequently, the prevalence of smoking among
pregnant women is estimated at 15% to 30%.