Research

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OBSTETRICS

Medical and obstetric complications among

pregnant women with cystic fibrosis
Emily M. Patel, MD; Geeta K. Swamy, MD; R. Phillips Heine, MD; Jeffrey A. Kuller, MD;
Andra H. James, MD, MPH; Chad A. Grotegut, MD, MHS
OBJECTIVE: The objective of this study was to estimate the nationwide

prevalence of cystic fibrosis (CF) in pregnancy and determine what

medical complications exist at delivery among pregnant women with CF.
STUDY DESIGN: The Nationwide Inpatient Sample (NIS) was queried
for all delivery-related discharges. Women with CF were identified by
International Classification of Diseases, 9th revision, Clinical Modifications codes and compared with women without CF. The prevalence
of selected severe medical complications was compared between the
2 groups (NIS years 2008-2010) using multivariable logistic regression and the linear change in prevalence of CF at delivery determined
(NIS years 2000-2010).
RESULTS: From 2000 to 2010, there was a significant linear increase

in the prevalence of CF at delivery from 3.0 to 9.8 per 100,000 deliveries, in 2000 and 2010, respectively (R2 0.92, P < .0001). From
2008-2010, there were 1119 deliveries to women with CF and

12,627,627 to women without CF. Women with CF were more likely to

be white (P < .0001) and have diabetes (odds ratio [OR], 14.0; 95%
confidence interval [CI], 11.8e16.7) or asthma (OR, 5.1; 95% CI,
4.3e6.1). Multivariable logistic regression demonstrated that women
with CF were more likely to die (adjusted OR [aOR], 76.0; 95% CI,
31.6e183), require mechanical ventilation (aOR, 18.3; 95% CI,
10.8e31.2), or have pneumonia (aOR, 56.5; 95% CI, 43.274.1),
acute renal failure (aOR, 17.3; 95% CI, 9.1e32.6), preterm labor
(aOR, 2.2; 95% CI, 1.9e2.6), or an adverse composite CF outcome
(aOR, 28.1; 95% CI, 21.8e36.3).
CONCLUSION: Pregnant women with CF are more likely to die, require

mechanical ventilation, and have infectious complications compared

with women without CF, although the absolute risks are low and these
events are relatively rare.
Key words: cystic fibrosis, morbidity, mortality, pregnancy

Cite this article as: Patel EM, Swamy GK, Heine RP, et al. Medical and obstetric complications among pregnant women with cystic fibrosis. Am J Obstet Gynecol
2015;212:98.e1-9.

ystic brosis (CF) is an autosomal

recessive disorder that affects 1 in
3500 live births in North America.1
Nearly 2000 different gene mutations
causing CF having been described with
an estimated gene prevalence of 1 in 25

From the Division of Maternal-Fetal Medicine,

Department of Obstetrics and Gynecology
(Drs Patel, Swamy, Heine, Kuller, and Grotegut),
Duke University School of Medicine, Durham,
NC, and Division of Maternal-Fetal Medicine,
Department of Obstetrics and Gynecology
(Dr James), University of Virginia School of
Medicine, Charlottesville, VA.
Received March 26, 2014; revised June 8, 2014;
accepted July 8, 2014.
The authors report no conict of interest.
Presented at the 34th annual meeting of the
Society for Maternal-Fetal Medicine, New
Orleans, LA, Feb. 3-8, 2014.
Corresponding author: Chad A. Grotegut, MD,
MHS. chad.grotegut@duke.edu
0002-9378/$36.00
2015 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ajog.2014.07.018

in whites and a less frequent carrier rate

among other ethnic/racial groups.2,3 The
disease is characterized by a disorder of
the cystic brosis transmembrane conductance regulator protein that leads to
abnormalities of the transmembrane
transport of chloride and sodium ions.4
This defect can affect multiple systems
and lead to viscous secretions and
impaired clearance in the respiratory,
gastrointestinal, and reproductive tracts.
Primary manifestations of the disease in
adults include respiratory failure from
chronic infections and inammation
and nutritional deciencies because of
malabsorption and pancreatic insufciency. Other manifestations of CF
include cirrhosis of the biliary tract,
diabetes mellitus, and male-factor
infertility.5
There have been substantial advances
in the care for individuals with CF
including improved nutrition and respiratory care. Women with CF are now
likely to survive into adulthood with the
median predicted survival at 36.8 years

98.e1 American Journal of Obstetrics & Gynecology JANUARY 2015

in 2011.6 Although earlier reports have

reported decreased fertility associated
with CF, more recent literature suggests
that the reproductive tract, pituitary and
ovarian hormones, and ovulatory function of women with CF is normal with
the exception of possible thickened
mucous in the cervical canal.4,7,8 If
women maintain appropriate weight
and lung function, there is little evidence
to suggest that fertility is reduced in this
population, thus providing women with
CF the opportunity for reproduction.9
With the improvement in life expectancy and more women with CF seeking
pregnancy, we sought to characterize
pregnancy outcomes among women
with CF. To date, most reports on outcomes among pregnant women with
CF have been from relatively small case
reviews of fewer than 100 pregnancies
obtained from CF registries or single
sites.10-22 Based on these and other
studies, experts believe that women with
CF who have moderate to good lung
function, dened as forced expiratory

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volume in 1 (FEV1) second 50-70%,
tolerate pregnancy well.10,13,14,23 The
aim of this study was to determine the
period prevalence of maternal CF and
estimate national medical and obstetric
outcomes among women with CF at
delivery using a nationwide administrative database.

M ATERIALS

AND

M ETHODS

The Nationwide Inpatient Sample (NIS)

from the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality was queried
for pregnancy-related discharges from
January 2008 through December 2010.
The NIS contains information from
approximately 8 million hospital stays
from over 1000 hospitals in 45 states
and is the largest all-payer inpatient care
database in the United States. The
sampling frame uses 5 strata including
ownership, hospital size, geographic
region, teaching status, and location
(urban or rural). The NIS is sampled
to approximate a 20% stratied sample
of US community hospitals. The data
are weighted to generate nationwide
estimates based on probabilities proportional to the number of hospitals
in each stratum. This accounts for
changes in the number of states included over the years and the different
hospitals sampled over time. The sampling frame comprises over 96% of the
US population.
Information contained in the NIS includes discharge diagnoses and procedure codes based on the International
Classication of Diseases, 9th revision,
Clinical Modications (ICD-9-CM). The
Agency for Healthcare Research and
Quality receives data from individual
states and insures data values are valid
and internally consistent. Further information about the NIS can be found
elsewhere.24 The information included
in the NIS contains safeguards to protect
the privacy of individual patients, physicians, and hospitals. Although the nature of the data is limited to discharge
diagnoses and demographic information, the NIS allows for the study of
relatively rare conditions. Because the
NIS excludes data elements that could
directly or indirectly identify individuals,

the study was deemed exempt by the

Duke University Health System Institutional Review Board (eIRB approval no.
Pro00045222).
Using the NIS for each of the
years 2008-2010, all delivery-related
discharge records were identied. We
focused only on admissions for delivery
to eliminate the possibility of counting a
woman more than once per pregnancy
in the analysis. There is a chance that
over the 3-year period, 1 woman may
have had 2 pregnancies and therefore be
represented twice in the study. Nonetheless, outcomes are unique for each
pregnancy and therefore there is value
in counting 1 woman with 2 different
pregnancies during that period. An
admission for delivery was dened as
any discharge record that included a
delivery code (ICD-9-CM codes 74.x
[except 74.91] for cesarean delivery and
V27, 72.x, 73.x, and 650-659 for general
delivery codes). Deliveries were also
identied by diagnosis-related group
codes. Diagnosis-related group codes
765 and 766 were used to identify cesarean deliveries and codes 767, 768,
774, and 775 for vaginal deliveries.25-29
Women with CF were identied by an
ICD-9-CM code of 277.0x and were
compared with women without CF. For
comorbidities, both the ICD-9-CM for a
particular condition in pregnancy (ie,
6xx code) and the general ICD-9-CM
codes for that condition were used
(Appendix; Supplementary Table for
ICD-9-CM codes used). A composite CF
outcome variable was created that
included any one of the following: death,
mechanical ventilation, sepsis, pneumonia, acute respiratory failure, acute
respiratory distress syndrome, or acute
renal failure. Data were weighted by the
sampling weights provided by the NIS.
Continuous variables were compared
between pregnant women with CF and
pregnant women without CF using Student t test or Wilcoxon sign rank tests
where appropriate. Logistic regression
was used to calculate odds ratios (ORs)
and 95% condence intervals (95% CIs)
for medical conditions and medical
and obstetric outcomes among women
with CF at delivery compared with
women without CF at delivery. Next, a

Research

FIGURE

Trend in the number of pregnant

women with cystic fibrosis per
100,000 deliveries

There was a significant linear increase in the

number of women with cystic fibrosis at delivery
from 2.99 per 100,000 deliveries in 2000
to 9.84 per 100,000 in 2010 (P < .0001,
R2 0.91).
Patel. Cystic brosis in pregnancy. Am J Obstet Gynecol 2015.

multivariable logistic regression model

was constructed for medical and obstetric outcomes among women with
CF whereas controlling for age, race/
ethnicity, diabetes, gestational diabetes,
hypertension, preeclampsia, multiple
gestation, and mode of delivery.
To determine the change in prevalence
of CF at delivery, delivery admissions
were identied using the NIS from the
years 2000 through 2010. A period of
11 years was chosen to allow for assessment of change over a longer time frame.
For each year, the number of women
with CF per 100,000 deliveries was
calculated. Linear regression was then
used to determine whether there was a
signicant linear change in the number
of women with CF at delivery over the
11-year time period.
Statistical signicance was assigned
as a P value of < .05. Analyses were
performed using SAS version 9.3 (SAS
Institute Inc, Cary, NC) and GraphPad
Prism version 6.0 for Macintosh
(GraphPad Software, La Jolla, CA).

R ESULTS
Over the years 2000 to 2010, there was a
signicant linear increase in the number
of women with CF at delivery from 2.99
per 100,000 deliveries in 2000 to 9.84 per

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TABLE 1

Demographic data among pregnant women with CF at delivery

CF
n [ 1119

No CF
n [ 12,627,627

OR (95% CI)

P value

794 (70.9)

5,570,518 (44.1)

1.0

African American

45 (4.0)

1,511,168 (12.0)

0.2 (0.2e0.3)

< .0001

Hispanic

70 (6.3)

2,426,137 (19.2)

0.2 (0.2e0.3)

< .0001

Asian/Pacific Islander

10 (0.9)

559,837 (4.4)

0.1 (0.1e0.2)

< .0001

Other

30 (2.7)

603,467 (4.8)

0.3 (0.2e0.5)

< .0001

170 (15.2)

1,956,499 (15.5)

Description
Race/Ethnicity, n (%)
White

Missing

26.5  13.5

Age, y

LOS, d

Total charges, $

27.6  13.7

3 (2, 4)
b

13,727 (8471, 26,494)

2 (2, 3)
10,002 (6785, 15,096)

.006

< .0001

< .0001

CF, cystic fibrosis; CI, confidence interval; LOS, length of stay; OR, odds ratio; SD, standard deviation.
a

Values are mean  SD; b Values are median (quartile).

Patel. Cystic brosis in pregnancy. Am J Obstet Gynecol 2015.

100,000 in 2010 (P < .0001; R2 0.91;

Figure). The years 2008 to 2010 were
then used to determine characteristics of
women with CF at delivery. Between
2008 and 2010, there were 12,628,746
deliveries identied in the NIS. Of those
deliveries, 1119 occurred in women with
a diagnosis of CF. Demographic characteristics of women with and without CF
are shown in Table 1. Women with CF
were more likely to be white and younger
compared with women without CF.
Race/ethnicity was missing for 15.2% of
women with CF and 15.5% of women
without CF. Women with CF also had a
longer median length of hospital stay (3
vs 2 days; P < .0001) and greater median
hospital charges ($13,727 vs $10,002;
P < .0001) (Table 1).
Table 2 describes preexisting medical
conditions among women with CF
compared with women without CF.
Women with CF were more likely to have
signicant medical comorbidities such
as asthma (OR, 5.1; 95% CI, 4.3e6.1;
P < .0001) and diabetes mellitus (OR,
14.0; 95% CI, 11.8e16.7; P < .0001).
Other ndings included increased incidence of cardiac conduction disorders
(OR, 5.5; 95% CI, 4.0e7.6; P < .0001)
and thrombophilia (OR, 5.7; 95% CI,
2.7e12.1; P < .0001).

Medical complications were common

among women with CF at the time of
delivery (Table 3). Women with CF had
increased odds of death and blood
transfusion compared with women
without CF at delivery. With regard to
respiratory complications, there was
increased odds of pneumonia, need for
mechanical ventilation, and acute respiratory failure. Women with CF were
more likely to have the adverse CF
outcome composite variable compared
with women without CF (OR, 35.3; 95%
CI, 28.6e43.5).
Next, we looked at obstetric events
at time of delivery. Women with CF
were more likely to have multiple gestation, operative vaginal delivery, gestational diabetes, and preterm labor
(Table 4). There was no difference in the
odds of cesarean delivery, preeclampsia/
eclampsia/gestational hypertension, placental abruption, fetal growth restriction,
or chorioamnionitis.
Using multivariable logistic regression to control for age, race/ethnicity,
multiple gestation, mode of delivery,
diabetes (gestational or pregestational),
chronic hypertension, and preeclampsia/
eclampsia, an adjusted analysis for
medical and obstetric complications was
performed (Table 5). Women with CF

98.e3 American Journal of Obstetrics & Gynecology JANUARY 2015

had an increased odds of death with an

adjusted OR (aOR) of 76.0 (95% CI,
31.6e183; P < .0001) compared with
women without CF. Increased odds of
mechanical ventilation, transfusion,
pneumonia, acute respiratory failure,
and acute renal failure among women
with CF remained signicant in our
adjusted model. The composite CF
outcome variable also remained significantly associated with CF in the
adjusted model (aOR, 28.1; 95% CI,
21.8e36.3). With regard to pregnancy
outcomes, women with CF had increased odds of preterm labor (aOR,
2.2; 95% CI, 1.9e2.6; P < .0001)
(Table 5). Odds of cesarean delivery,
preeclampsia/eclampsia/gestational hypertension, abruption, fetal growth restriction, postpartum hemorrhage, and
chorioamnionitis were not signicant.

C OMMENT
Cystic brosis is a pulmonary disorder
affecting 1 in every 3500 live births.1 As
life expectancy increases, and treatment
modalities improve, people with CF are
living well into their childbearing years
with average life expectancy reaching
40 years of age. Our ndings demonstrate an increasing number of pregnant
women with CF at delivery from the

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TABLE 2

Medical conditions present at time of delivery among women with CF

CF
n [ 1119

Condition, n (%)a

No CF
n [ 12,627,627

OR (95% CI)

P value

39 (3.5)

83,146 (0.7)

5.5 (4.0e7.6)

< .0001

Asthma

165 (14.7)

411,451 (3.3)

5.1 (4.3e6.1)

< .0001

Diabetes (nongestational)

Cardiac conduction
disorders

147 (13.1)

134,209 (1.1)

14.0 (11.8e16.7)

< .0001

Thyroid disorder

33 (2.9)

299,896 (2.4)

1.2 (0.9e1.7)

.24

Thrombophilia/APS

36 (3.2)

71,418 (0.6)

5.7 (2.7e12.1)

< .0001
.001

Anemia

154 (13.8)

1,363,611 (10.8)

1.3 (1.1e1.6)

Thrombocytopenia

11 (1.0)

114,686 (0.9)

1.1 (0.6e1.9)

.85

Drug use

14 (1.2)

165,626 (1.3)

0.9 (0.5e1.6)

.80

Tobacco

90 (8.0)

794,831 (6.3)

1.3 (1.04e1.6)

.02

APS, antiphospholipid antibody syndrome; CF, cystic fibrosis; CI, confidence interval; NIS, Nationwide Inpatient Sample; OR,
odds ratio.
a

The NIS does not allow reporting the number of cases when the cell frequency is less than or equal to 10. There were 10 or
fewer cases of chronic hypertension, systemic lupus erythematosus, rheumatoid arthritis, human immunodeficiency virus,
alcohol use, and chronic renal failure among women with CF.

Patel. Cystic brosis in pregnancy. Am J Obstet Gynecol 2015.

years 2000 to 2010 and that there is an

increased risk of morbidity and mortality associated with CF during pregnancy.
Eleven women with CF died during an
admission for delivery over the 3-year
period from 2008-2010. This represents
a maternal death rate at delivery of
approximately 1000 deaths per 100,000
deliveries compared with approximately
7.3 deaths per 100,000 deliveries to

women without CF. In addition, serious

morbidities such as mechanical ventilation and acute renal failure were high
among women with CF. Obstetric outcomes were also impacted with increased
odds of preterm labor. However, we did
not identify any difference in rates of
cesarean delivery and other adverse obstetric outcomes such as fetal growth
restriction and fetal demise.

TABLE 3

Medical events present at time of delivery among women with CF

Condition, n (%)a

CF
n [ 1119

No CF
n [ 12,627,627

Death

11 (1.0)

Mechanical ventilation

25 (2.2)

Transfusion

20 (1.8)

131,684 (1.0)
13,150 (0.1)

921 (0.007)
9003 (0.07)

OR (95% CI)

P value

125 (67e233)

< .0001

31.9 (21.4e47.5)

< .0001

1.7 (1.1e2.7)

.01

Pneumonia

75 (6.7)

68.7 (54.3e86.9)

< .0001

Acute respiratory failure

14 (1.2)

5450 (0.04)

29.6 (16.7e48.0)

< .0001

Acute renal failure

11 (1.0)

7075 (0.06)

16.4 (8.9e30.4)

< .0001

95 (8.5)

33,275 (0.26)

35.3 (28.6e43.5)

< .0001

Composite CF outcome

CF, cystic fibrosis; CI, confidence interval; NIS, Nationwide Inpatient Sample; OR, odds ratio.
a

The NIS does not allow reporting the number of cases when the cell frequency is less than or equal to 10. There were 10 or
fewer cases of myocardial infarction, cardiac arrest, acute heart failure, pulmonary edema, acute respiratory distress
syndrome, pulmonary embolism, deep vein thrombosis, stroke/cerebral vascular accident, sepsis, pyelonephritis and
influenza among women with CF; b Composite CF outcome includes any of the following: death, mechanical ventilation,
sepsis, pneumonia, acute respiratory failure, acute respiratory distress syndrome, or acute renal failure.

Patel. Cystic brosis in pregnancy. Am J Obstet Gynecol 2015.

Research

Women with CF at delivery were

found to have higher rates of thrombophilia compared with women without
CF. Williams et al30 in 2010 demonstrated an increased thrombophilic tendency by laboratory analysis in a
pediatric CF population. They found a
marked increase in lupus anticoagulants
(18% vs 3-8% expected in the population), and protein C (14% vs <1%
expected) and protein S deciencies
(19.7% vs <1% expected) in pediatric
CF patients. Although there were no
clinically noted thrombotic events in the
pediatric study population, this may be
signicant given the frequent use of
intravenous lines and indwelling catheterization among CF patients. According
to a study by Balfour-Lynn et al31 in
2006, there are no inherited thrombophilias associated with CF, however, it is
thought that the presence of infection
or inammation in CF patients may lead
to acquired thrombophilias. Although
this is of potential concern given the
thrombogenic state of pregnancy, the
relevance is yet unknown. It is possible
that women with CF are more likely to be
screened for inherited or acquired
thrombophilias because of their chronic
medical condition, thus accounting for
the ndings. In our study, we were unable to recognize any difference in risk
for thromboembolic phenomena among
pregnant women with CF compared
with those without as there were too few
or no cases of deep venous thrombosis,
pulmonary embolism, or stroke among
women with CF.
In addition to thrombophilias,
women with CF were more likely to have
a diagnosis of diabetes. This is not surprising as up to 25% of CF patients
develop diabetes by the age of 20 because
of both decreased insulin production
by the pancreas and relative insulin
resistance.32,33 Given this signicant risk
factor, women with CF in pregnancy
who do not have a diabetes diagnosis
should undergo early glucola screening.
In our study population, women with
CF had signicant odds for dying during
an admission for delivery. Of the 1119
women with CF included in this analysis,
11 died giving a mortality rate of
approximately 1%. Our study analyzed

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TABLE 4

Obstetric events present at time of delivery among women with CF

Condition, n (%)a

CF
n [ 1119

No CF
n [ 12,627,627

OR (95% CI)

P value

Cesarean delivery

351 (31.4)

4,041,005 (32.0)

1.0 (0.9e1.1)

.67

Operative vaginal delivery

100 (8.9)

792,143 (6.3)

1.5 (1.2e1.8)

.0002

39 (3.5)

267,193 (2.1)

1.7 (1.2e2.3)

.0013

148 (13.2)

714,940 (5.7)

2.5 (2.1e3.0)

< .0001

76 (6.8)

931,154 (7.4)

0.9 (0.7e1.1)

.48

1,051,494 (8.3)

2.5 (2.2e2.9)

< .0001

Multiple gestation
GDM
Preeclampsia, eclampsia,
gest HTN
Preterm labor

209 (18.7)

Abruption

16 (1.4)

136,053 (1.1)

1.3 (0.8e2.2)

.22

Fetal growth restriction

29 (2.6)

271,882 (2.2)

1.2 (0.8e1.8)

.26

Postpartum hemorrhage

15 (1.3)

321,959 (2.5)

0.5 (0.3e0.9)

.012

Chorioamnionitis

36 (3.2)

323,531 (2.6)

1.3 (0.9e1.8)

.17

CF, cystic fibrosis, CI, confidence interval; GDM, gestational diabetes; gest HTN, gestational hypertension; NIS, Nationwide
Inpatient Sample; OR, odds ratio.
a

The NIS does not allow reporting the number of cases when the cell frequency is less than or equal to 10. There were 10 or
fewer cases of fetal demise and placenta previa among women with CF.

Patel. Cystic brosis in pregnancy. Am J Obstet Gynecol 2015.

only deaths occurring at delivery. Using

the NIS, we went back to see if any
additional deaths to women with CF
occurred during an antepartum or postpartum admission and there were none.
All maternal deaths among women with
CF found in the NIS occurred at the time
of delivery. In comparison, we did not
identify all maternal deaths occurring to

women without CF during the years

2008-2010. Maternal mortality is dened
by the Centers for Disease Control and
Prevention as a maternal death occurring
during pregnancy or within 42 days from
delivery.34 Because of limitations in
identifying postpartum discharges in
relation to time frame from delivery, we
chose to only analyze deaths, as well as

TABLE 5

Multivariable logistic regression model for complications among women

with CF
Maternal condition

Adjusted OR (95% CI)

P value

Death

76.0 (31.6e183)

< .0001

Mechanical ventilation

18.3 (10.8e31.2)

< .0001

Transfusion

1.68 (1.01e2.81)

.045

Pneumonia

56.5 (43.2e74.1)

< .0001

Acute respiratory failure

20.3 (10.5e39.0)

< .0001

Acute renal failure

17.3 (9.1e32.6)

< .0001

Composite CF outcome

28.1 (21.8e36.3)

< .0001

2.2 (1.9e2.6)

< .0001

Preterm labor

Multivariable logistic regression analysis for the listed outcomes among women with CF at delivery while controlling for age,
race/ethnicity, diabetes, hypertension, gestational diabetes, preeclampsia, multiple gestation, and mode of delivery.
CF, cystic fibrosis; CI, confidence interval; OR, odds ratio.
Patel. Cystic brosis in pregnancy. Am J Obstet Gynecol 2015.

98.e5 American Journal of Obstetrics & Gynecology JANUARY 2015

medical complications, that occurred

during an admission in which a delivery
occurred. Though we did not identify any
postpartum (or antepartum) deaths to
women with CF, it is possible that mortality rates occurring in the postpartum
period following discharge could be
different by CF status. Among pregnant
women with CF who died during the
hospitalization in which a delivery occurred, it is not possible to determine
if they were admitted primarily because
of a complication of CF, such as pneumonia or infection, and delivery then
happened to occur during the same
admission, or if they were admitted primarily for an obstetric indication and a
complication leading to death occurred.
The rst listed diagnosis in the NIS
is considered the primary diagnosis.
Among women who died during a hospitalization in which a delivery occurred,
pulmonary and infection diagnoses were
common principle diagnoses. Despite
this, it is not possible to determine
whether these were the true indications
for admission rather than an obstetric
reason.
Recent studies have indicated that
maternal death among pregnant women
with CF is rare and pregnancy does not
impact overall survival rates. The largest
study of women with CF in pregnancy
prior to ours was by Goss et al22 in 2003
in which 680 women of a cohort of
8136 women with CF became pregnant.
The 680 pregnant women were matched
to nonpregnant control women with
CF. Pregnant women with CF did not
have a decreased 10-year survival rate
compared with age-matched controls,
even after controlling for FEV1, age, and
diabetes.22 However, this comparison
was between pregnant women with CF
to nonpregnant women with CF rather
than comparing pregnant women with
CF with pregnant women without. In
addition, the study by Goss et al22 was
looking at 10-year survival, not peripartum mortality as we have in this
analysis. Kent and Farquharson35 published a review of case reports and case
series of CF in pregnancy in 1993 and
found a reported death rate of 8%
within 6 months of delivery and 13.6%
within 2 years following delivery,

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though the review included only 162
women with CF.
Our data demonstrate that the number of women with CF who become
pregnant has steadily increased since
2000. The American College of Obstetricians and Gynecologists released a
monograph with the American College
of Medical Genetics in 2001 recommending the routine screening of all
white pregnant women for CF carrier
status.36 Since then, American College of
Obstetricians and Gynecologists now
recommends that CF carrier screening
be offered to all women.37 Therefore, the
number of women identied as being CF
carriers over the last 10 to 15 years has
likely increased. In our study, though
unlikely, it is unknown if some women
who are CF gene carriers (V83.81), were
miscoded as having CF when in fact, they
were carriers. In addition, it is possible
that genetic testing has expanded the
number of women who are diagnosed
with CF. As a consequence, individuals
with a milder phenotype may be diagnosed who would not have been diagnosed with the disease in the past.
However, over 70% of CF mutations are
the DeltaF508 mutation, which is typically associated with more severe disease.38 Given this, the maternal mortality
rate quoted in our study is likely representative of women with a more severe
phenotype and does not include women
coded as CF carrier.
Our study has limitations. Using a
large discharge database requires dependence on ICD-9 coding. We depend
on the accurate coding for the medical
and obstetric conditions we evaluated.
Some outcomes, such as death or mechanical ventilation are unlikely to be
miscoded. However, there is no way of
knowing if certain comorbidities were
missed that were not coded at the time of
discharge. Further, it is possible that
medical comorbidities may be more
likely to be coded among women with
CF than in those without CF. Therefore,
we may be underrepresenting some
complications among women who do
not have CF. In addition, we are unable
to determine causality between CF and
poor outcomes because of the cross-

sectional nature of the study and the

use of an administrative database.
In the literature, FEV1 is the strongest
predictor of outcome among women
with CF in pregnancy. Because of the
nature of the database, we do not know
what the maternal FEV1 status or prepregnancy health was in each woman
and, therefore, cannot make conclusions
about the women at potentially highest
risk. We are also unable to identify
women who may have had a more severe
vs mild phenotype. Last, we are unable to
link neonatal discharge records with
maternal records through the NIS.
Therefore, we are unable to analyze
neonatal outcomes among women with
CF. Despite these limitations, use of the
NIS database, particularly in this study,
allows for the investigation of relatively
rare disorders and outcomes such as
cystic brosis and death.
In summary, women with CF are at
risk for morbidity and mortality in
pregnancy and the number of women
with CF at delivery has increased
signicantly over the last decade. It is
generally felt that women with CF are
good candidates for pregnancy if they
have intermediate to good pulmonary
function at the start of the pregnancy
(most agree FEV1 above 50-70%) and
this has been felt to be the strongest
predictor of maternal morbidity and
mortality.11,14,15,23 Although we do not
have information for this study to
correlate outcomes with maternal disease status, the results are nonetheless
striking. Women with CF have a significantly increased risk of death during
pregnancy as compared with women
without the diagnosis of CF. It is, however, important to remember, as demonstrated in other studies, that women
with CF who are in good health with a
normal FEV1 at the start of pregnancy
are at low risk for mortality. Women
with CF are also at increased risk of infectious morbidity, need for mechanical
ventilation, acute renal failure, and
poor obstetric outcomes such as preterm
labor. This study can help guide the
practitioner in counseling women with
CF who are or desire to become
pregnant.
-

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Research

A PPENDIX

SUPPLEMENTARY TABLE

ICD-9 codes for prexisting medical conditions, medical events, and

obstetric complications used to identify cases in the NIS 2008e2010
Medical condition

ICD-9 codes

Heart disease
Conduction disorders

426.0e426.9, 427.0e427.4, 427.6e427.9,

785.0, 785.1, V45.0, V53.3

History of myocardial infarction or

chronic ischemic heart disease

412, 414

Pulmonary Disease
Asthma

493.x

Endocrine
Diabetes (nongestational)

249.x, 250.x, 648.0x

Thyroid disease

240.xe246.x, 648.1x

Autoimmune
Systemic lupus erythema.

710.0, 695.4, 583.8

Rheumatoid arthritis/collagen disease

701.0, 710, 710.1xe710.9x, 714.x, 720.x,

725

Hematologic
Thrombophilia (includes history of
thrombosis and antiphospholipid
syndrome [APS])

273.8, 286.53, 286.9, 289.81, 289.82,

V12.51

Anemia

648.2x, 280.x, 285.x

Thrombocytopenia

287.3x, 287.4x, 287.5x

Drug/Alcohol/Tobacco
Drug use

292.x, 304.x, 305.2x-305.9x, 655.5x,

760.70, 760.72e760.75, 779.5, 965.0x,
V65.42

Alcohol use

291.x, 303.x, 305.0x, 760.71, 980.0x

Smoking

305.1, V15.82, 649.0x

Chronic hypertension/renal failure

Chronic hypertension

401.xe405.x, 437.2, 642.0xe642.2x

Chronic renal failure

585.x, 792.5, V42.0, V45.1, V56.x

Event or condition
Mechanical ventilation

Procedure codes: 93.90, 96.01e96.05,

96.7x

Transfusion

V58.2, Procedure codes: 99.00e99.09

Cardiac event
Myocardial infarction/ischemia

410.x, 411.x

Cardiac arrest/ventricular fibrillation

427.41, 427.42, 427.5

Heart failure

428.x

Patel. Cystic brosis in pregnancy. Am J Obstet Gynecol 2014.

(continued)

JANUARY 2015 American Journal of Obstetrics & Gynecology

98.e8

Research

Obstetrics

ajog.org

SUPPLEMENTARY TABLE

ICD-9 codes for prexisting medical conditions, medical events, and

obstetric complications used to identify cases in the NIS 2008e2010
(continued)

Medical condition

ICD-9 codes

Pulmonary event
Pneumonia

480.xe486.x, 487.0

Pulmonary edema

518.4

Acute respiratory distress syndrome

518.5

Thromboembolic event
Pulmonary embolism

415.1x, 673.x

Deep venous thrombosis

451.1x, 451.2x, 671.3x, 671.4x

Stroke/cerebrovascular disorders

325, 430, 431, 432.x, 433.x, 434.x, 436,

437.x, 671.5x, 674.0x, 997.2, 999.2

Infections
Sepsis

038.x, 790.7

Influenza

487.xe488.x

Renal event
Acute renal failure

584.x, 639.3x, 669.3x

Obstetric events
Multiple gestation

651.x, 652.6x, V27.2eV27.7

Operative vaginal delivery

Procedure codes: 720e724, 726,

727e727.9

Gestational diabetes

648.8x

Preeclampsia, eclampsia or
gestational hypertension

642.3xe642.7x

Preterm labor

644.x

Placental abruption

641.2x

Fetal growth restriction

656.5x

Intrauterine fetal death

656.4x

Placenta previa

641.0e641.1x

Postpartum hemorrhage

666e666.2x

Chorioamnionitis

658.4x, 659.2x

ICD-9CM, International Classification of Diseases, Ninth Revision, Clinical Modification; NIS, Nationwide Inpatient Sample.
Patel. Cystic brosis in pregnancy. Am J Obstet Gynecol 2014.

98.e9 American Journal of Obstetrics & Gynecology JANUARY 2015