Research

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OBSTETRICS

Hypertension and antihypertensive drugs

in pregnancy and perinatal outcomes
Hagay Orbach, MD; Ilan Matok, PhD; Rafael Gorodischer, MD; Eyal Sheiner, MD, PhD; Sharon Daniel, MD, MPH;
Arnon Wiznitzer, MD; Gideon Koren, MD; Amalia Levy, MPH, PhD
OBJECTIVE: Despite high rates of hypertension in pregnancy, the ef-

fects of hypertension have not been separated appropriately from the

effects of the medications that are used. We evaluated the safety of exposure to antihypertensive medications during pregnancy, while accounting for disease effects.
STUDY DESIGN: A population-based retrospective cohort study was performed that compared all pregnancies of women with hypertension who
were either exposed or unexposed to antihypertensive medications. A computerized database of the medications that were dispensed to pregnant
women from 1998-2008 was linked with computerized databases that
contained maternal and infant hospitalization records from the district
hospital during the same period.
RESULTS: During the study period, 100,029 deliveries occurred; of

those, 1964 pregnant women experienced chronic hypertension, and

620 neonates (0.6%) were exposed to at least 1 antihypertensive medication (methyldopa or atenolol) during pregnancy. A higher rate of in-

trauterine growth restriction (7.2% vs 2.1%, respectively; adjusted

odds ratio [OR], 4.37; 95% confidence interval [CI], 3.00 6.36; P
.001), small for gestational age (3% vs 1.7%, respectively; adjusted
OR, 2.23; 95% CI, 1.273.92; P .005), and preterm deliveries (37
weeks, 22.9% vs 8.0%, respectively; adjusted OR, 3.69; 95% CI,
2.90 4.69; P .001) were noted among the pregnancies of women
who were exposed to antihypertensive medications during the third trimester. Importantly, a similar association was detected when we compared women with chronic hypertension who were not treated during
pregnancy (n 1074) to women who had no chronic hypertension and
who were unexposed to antihypertensive medications (n 97,820).
CONCLUSION: Chronic hypertension with or without treatment during

pregnancy is an independent and significant risk factor for adverse perinatal outcomes such as intrauterine growth restriction, small for gestational age, and preterm delivery.
Key words: atenolol, chronic hypertension, methyldopa, pregnancy

Cite this article as: Orbach H, Matok I, Gorodischer R, et al. Hypertension and antihypertensive drugs in pregnancy and perinatal outcomes. Am J Obstet Gynecol
2013;208:301.e1-6.

hronic hypertension is defined as

blood pressure that exceeds 140/90
mm Hg at 20 weeks gestation or that
persists longer than the usual postpartum
period (12 weeks after delivery).1,2 It is a

serious medical condition that complicates 1-5% of all pregnancies and that is
associated with an increased risk for maternal and fetal morbidity and death.1,2
The most common maternal complica-

From the Departments of Public Health (Drs Orbach, Daniel, and Levy), Pediatrics (Dr
Gorodischer), and Obstetrics and Gynecology (Drs Sheiner and Wiznitzer), Faculty of Health
Sciences, Ben-Gurion University of the Negev; Soroka Medical Center (Drs Gorodischer,
Sheiner, and Wiznitzer); and Clalit Health Services (Southern District) (Drs Gorodischer and
Wiznitzer), Beer-Sheva, Israel; the Center for Clinical Epidemiology, Lady Davis Research
Institute, Jewish General Hospital, and the Department of Epidemiology, Biostatistics, and
Occupational Health, McGill University, Montreal, QC (Dr Matok), and the Motherisk Program,
Division of Clinical Pharmacology-Toxicology, Department of Pediatrics, The Hospital for Sick
Children, and University of Toronto, Toronto, ON (Dr Koren), Canada; and the BeMORE (BenGurion Motherisk Obstetric Registry of Exposure) collaboration (Drs Matok, Gorodischer,
Daniel, Koren, and Levy).
Received July 31, 2012; revised Nov. 1, 2012; accepted Nov. 13, 2012.
The authors report no conflict of interest.
Presented as a poster at the annual meeting of the Canadian Society of Pharmacology and
Therapeutics, Montreal, QC, Canada, May 25-27, 2011.
Reprints: Amalia Levy, MPH, PhD, Public Health Department, Faculty of Health Sciences, BenGurion University of the Negev, POB 653, Beer Sheva 84105. Israel.lamalia@bgu.ac.il.
0002-9378/$36.00 2013 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2012.11.011

See Journal Club, page 331

tion that involves 25% of the cases is superimposed preeclampsia.2 Other possible maternal complications include
placental abruption, the need for cesarean delivery, and even death.3,4 The most
common fetal complications are intrauterine growth restriction (IUGR),
small-for-gestational-age (SGA) newborn infants, and prematurity.4-6 The incidence of these adverse effects is related
to the degree and duration of hypertension and to the involvement of other organs.7 Studies have shown that, even after
adjustment for superimposed preeclampsia as a risk factor for fetal and maternal
morbidities, pregnancies that are complicated with chronic hypertension have
higher rates of cesarean deliveries, IUGR,
perinatal mortality, and postpartum hemorrhage.8 Several risk factors that have
been reported to aggravate the prevalence
of chronic hypertension include maternal
obesity, diabetes mellitus, heredity, and racial factors. Another risk factor is advanced
maternal age.8

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The common drugs that are used in the

treatment of chronic hypertension during
pregnancy are methyldopa or atenolol.
Methyldopa is an 2 adrenergic agonist.
Activation of these receptors in the central
nervous system inhibits sympathetic output that leads to a decrease in blood pressure.9,10 Atenolol is a selective 1 adrenergic inhibitor with a negative chronotropic
and inotropic effect on the myocardium.9,10 A number of studies have documented the efficacy of treatment for
chronic hypertension during pregnancy;
nevertheless, an important question that has
not yet been resolved is the independent effects of nontreated hypertension.11-17 Despitehighratesofhypertensioninpregnancy,
the effects of hypertension have not been
separated appropriately from those of
the medications that have been used. Because of the increasing rates of maternal
obesity and the trend to postpone pregnancies to older ages, there is an increasing incidence of chronic hypertension,
which might contribute to maternal and
fetal morbidities. The objective of the
present study was to separate the effects
of hypertension from its treatments on
adverse pregnancy outcomes.

M ETHODS
This was a retrospective cohort study
that involved members of Clalit Health
services in southern Israel. Clalit is the
largest health maintenance organization
in Israel, in which 70% of the district
population (which includes 70% of
women 15-49 years old) is insured. The
population of the Southern District of Israel is slightly greater than one-half a
million citizens. Soroka Medical Center
(SMC) is the district hospital in which
practically all deliveries of the region take
place.18,19 All infants are examined by a
board-certified neonatologist.
The clinical, medication, and demographic data of Clalit members are stored
in the Clalit data warehouse and can be
queried at the level of an individual member. This database contains information
about dispensing date, the Anatomical
Therapeutically Classification code of the
drug (including the commercial and generic names), dose schedule of drugs administration, and dose dispensed in de301.e2

www.AJOG.org
fined daily dose (the assumed average
maintenance dose per day).
Two computerized SMC databases
that draw information directly from
original sources were used. All patient
records at SMC originate from a single
database that includes demographic information and hospitalization dates that
are generated at the time of the womans
admission to the hospital and of the infants birth. The database of the Obstetrics and Gynecology Department includes information on maternal medical
conditions during pregnancy and delivery, maternal age, gestational age at delivery (in days since last menstrual period), perinatal death, parity, ethnic
group, self-reported smoking status during pregnancy, infant birthweight, and
Apgar score at 1 and 5 minutes. The diagnoses are reviewed routinely by a
trained medical secretary before entry
into the database. The other electronic
SMC database that was used in the present study was the Demog-International
Classification of Diseases, Ninth Revision
(ICD9) database, which includes demographic and medical diagnoses during
hospitalization; the latter is drawn directly from the medical records. Additional infant diagnoses that were recorded on discharge are coded and
included into their Demog-ICD9 record.
All diagnoses are classified according to
the ninth revision of the ICD.
Women from 15-49 years old who were
registered with Clalit and who lived in the
southern district of Israel who gave birth at
SMC were included. The study period was
January 1998 to August 2008, during
which 100,029 deliveries took place. Approximately one-half of the infants in the
district were born to Jewish parents and
one-half of the infants were born to Bedouin parents. The southern district of Israel is populated by 2 distinct ethnic
groups, the Jewish and the Bedouins Arabs. Because consanguinity is practiced
widely in the Bedouin population, their
babies are at higher risk for congenital malformations. The 3 databases (1 from Clalit
and 2 from SMC) described earlier were
encoded and linked by a personal identification number to create a registry of medications that were dispensed during pregnancy and the pregnancy outcomes.

American Journal of Obstetrics & Gynecology APRIL 2013

We investigated the relationship between exposure to antihypertensive

drugs during pregnancy and perinatal
outcomes, specifically IUGR, preterm
delivery (PTD; 37 weeks gestation),
congenital malformations, and low
birthweight (LBW; 2500 g). The exposed group included women to whom
antihypertensive (methyldopa or atenolol) drugs were dispensed during the
first trimester of pregnancy (13 weeks
gestation). We also assessed methyldopa
and atenolol individually. The unexposed group comprised all women without diagnosis of chronic hypertension
and who were not exposed to antihypertensive drugs through the first or the
third trimester during the study period.
The nontreated hypertension group included all women with a diagnosis of
chronic hypertension who were not
treated for hypertension during the index pregnancy.
Congenital malformations data were
obtained from SMC databases. We used
the definitions of major congenital malformations that had been developed by the
Centers for Disease Control and Prevention Metropolitan Atlanta Congenital Defects Program.20,21 This program has been
conducting surveillance for birth defects
since 1967, and its definitions have been
validated in several previous studies.21
Chromosomal diseases were excluded.
The following pregnancy outcomes were
investigated in both live neonates and stillborn infants: major malformations, perinatal death, PTD, LBW (2500 g), very
LBW (1500 g), and Apgar score at 1 and
5 minutes after birth (categorized as Apgar
7 or 8), and preeclampsia. The following potential confounders were included
in the statistical analysis: maternal age, parity, self-reported smoking in pregnancy,
maternal diabetes mellitus, lack of prenatal
care, and ethnicity (ie, Jewish or Bedouin
Moslem). The study was approved by the
institutional Helsinki Ethics Committee
for Human Investigations. No written informed consent was required.
The statistical analyses were performed with the SPSS package (version
18; SPSS Inc, Chicago, IL). The exposed
group was compared with the unexposed by means of chi-square test or
Fishers Exact test for differences in cat-

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Research

TABLE 1

Characteristics of women who were and were not exposed to hypertensive

medications in the first and the third trimester of pregnancya

Characteristic

Exposure to antihypertensive medication during

the first trimester of pregnancy

Exposure to antihypertensive medication

during the third trimester of pregnancy

No (n 97,820)

No (n 97,820)

Yes (n 271)

P value

Yes (n 433)

.001

Ethnic group, n (%)

P value
.001

.......................................................................................................................................................................................................................................................................................................................................................................

Jews

34,475 (35.2)

135 (49.8)

34,475 (35.2)

213 (49.2)

Bedouins

63,345 (64.8)

136 (50.3)

63,345 (64.8)

220 (50.8)

.......................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................
b

28.51 5.8

Maternal age, y

34.85 5.5

.001

28.5 5.8

33.4 5.5

.001

5691 (5.8)

121 (27.9)

.726

2302 (2.4)

6 (1.4)

.001

................................................................................................................................................................................................................................................................................................................................................................................

Maternal diabetes mellitus, n (%)

5691 (5.8)

68 (25.1)

Smoking, n (%)

2302 (2.4)

5 (1.8)

.001

................................................................................................................................................................................................................................................................................................................................................................................

.243

................................................................................................................................................................................................................................................................................................................................................................................
b

3.5 2.6

Parity, n

5.2 3.6

.001

3.7 2.6

4.7 3.3

.001

................................................................................................................................................................................................................................................................................................................................................................................
a

Women with nontreated hypertension were not included; Data are given as mean SD.
b

Orbach. Hypertension/antihypertensive drugs in pregnancy/perinatal outcomes. Am J Obstet Gynecol 2013.

egoric variables and the Student t test for

differences in continuous variables.
Multivariate logistic regression models
were constructed to identify independent risk factors that were associated
with adverse pregnancy outcomes. Multivariate logistic regression models were
performed to investigate whether greater
exposure was associated with increased
risk of IUGR, PTD, congenital malformations, and SGA. Odd ratios (ORs) and
their 95% confidence intervals (CIs)
were computed.

R ESULTS
During the study period, 100,029 deliveries occurred. Six hundred twenty
women (0.6%) with chronic hypertension were exposed to atenolol or methyldopa or both during the index pregnancy; 271 women (0.2%) were exposed to
atenolol or methyldopa or both during
the first trimester of pregnancy; 114
women (0.11%) were exposed to methyldopa, and 188 women (0.18%) were
exposed to atenolol. One thousand sev-

enty-four women (1.07%) experienced

chronic hypertension during pregnancy
but were not exposed to antihypertensive
medication. Five hundred fifteen infants
who were exposed to antihypertensive
drugs in utero for maternal indications
other than hypertension were excluded
from the cohort.
Characteristics of the mother exposed
and unexposed to antihypertensive medications are presented in Table 1. Of the
infants who were born, 4623 infants were
born with congenital malformations; of

TABLE 2

Comparison of pregnancy and perinatal outcomes of exposed and unexposed women

and fetuses to antihypertensive medications in the third trimester of pregnancy
Exposure to antihypertensive
medication during the third
trimester of pregnancy, n (%)a

Exposure to methyldopa during

the third trimester of pregnancy, n
(%)

Exposure to atenolol during the

third trimester of pregnancy, n (%)

No
(n 97,820)

Yes
(n 433)

No
(n 97,820)

Yes
(n 340)

P
value

No
(n 97,820)

Yes
(n 107)

P
value

Preterm delivery

7836 (8.0)

99 (22.9)

.001

7836 (8.0)

86 (25.3)

.001

7836 (8.0)

18 (16.8)

.001

Low birthweight

10,001 (10.2)

104 (24.0)

.001

10,001 (10.2)

84 (24.7)

.001

10,001 (10.2)

25 (23.4)

.001

Perinatal death

1379 (1.4)

9 (2.1)

1379 (1.4)

9 (2.6)

1379 (1.4)

0 (0.0)

Variable

P
value

................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................

.158

.035

................................................................................................................................................................................................................................................................................................................................................................................

Apgar score 7

.......................................................................................................................................................................................................................................................................................................................................................................
b

.001

5790 (6.1)

43 (12.8)

10 (2.3)

.012

1026 (1.1)

31 (7.2)

.001

2096 (2.1)

At 1 min

5790 (6.1)

55 (12.9)

At 5 min

1026 (1.1)

Intrauterine growth
restriction

2096 (2.1)

Small for gestational age

1704 (1.7)

13 (3.0)

Preeclampsia

1093 (1.1)

60 (13.9)

.001

5790 (6.1)

10 (3.0)

.001

1026 (1.1)

24 (7.1)

.001

2096 (2.1)

9 (8.4)

.001

15 (14.2)

.001

.......................................................................................................................................................................................................................................................................................................................................................................
c
................................................................................................................................................................................................................................................................................................................................................................................

................................................................................................................................................................................................................................................................................................................................................................................

.005

1704 (1.7)

8 (2.4)

.001

1093 (1.1)

53 (15.6)

.06

1704 (1.7)

6 (5.6)

.001

1093 (1.1)

10 (9.3)

.001

................................................................................................................................................................................................................................................................................................................................................................................

.001

................................................................................................................................................................................................................................................................................................................................................................................
a

Exposed at least 1 time to atenolol or methyldopa; b 2333 infants had no 1-minute Apgar score; c 2232 infants had no 5-minute Apgar score.

Orbach. Hypertension/antihypertensive drugs in pregnancy/perinatal outcomes. Am J Obstet Gynecol 2013.

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TABLE 3

Crude and adjusted odds ratios for pregnancy adverse outcomes after exposure
of fetuses to antihypertensive medications in the third trimester of pregnancya

Variable

Exposure to antihypertensive medication

during the third trimester of pregnancy

Exposure to methyldopa during the

third trimester of pregnancyb

Exposure to atenolol during the

third trimester of pregnancyc

Crude odds ratio

(95% CI)

Crude odds ratio

(95% CI)

Adjusted odds ratio

(95% CI)

Crude odds ratio

(95% CI)

Adjusted odds ratio

(95% CI)

Adjusted odds ratio

(95% CI)

Preterm delivery

3.40 (2.724.27)

3.69 (2.904.69)

3.89 (3.044.97)

4.19 (3.225.45)

2.32 (1.403.86)

2.68 (1.574.56)

Low birthweight

2.78 (2.223.46)

3.68 (2.894.67)

2.88 (2.253.69)

3.77 (2.894.94)

2.68 (1.714.19)

3.89 (2.426.25)

Perinatal death

1.48 (0.772.88)

1.62 (0.833.15)

1.90 (0.983.70)

2.05 (1.054.02)

................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................

Apgar score 7

.......................................................................................................................................................................................................................................................................................................................................................................

At 1 min

2.29 (1.723.04)

2.03 (1.522.72)

2.28 (1.653.14)

1.95 (1.402.70)

2.56 (1.484.42)

2.65 (1.524.61)

At 5 min

2.21 (1.184.14)

2.27 (1.204.28)

2.83 (1.505.32)

2.84 (1.505.38)

Intrauterine growth
restriction

3.52 (2.445.09)

4.37 (3.006.36)

3.47 (2.295.27)

4.32 (2.826.61)

4.19 (2.128.31)

5.19 (2.5910.39)

Small for
gestational age

1.75 (1.003.04)

.......................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................

................................................................................................................................................................................................................................................................................................................................................................................

2.23 (1.273.92)

1.36 (0.672.75)

1.01 (1.001.02)

3.35 (1.477.65)

4.80 (2.0711.10)

................................................................................................................................................................................................................................................................................................................................................................................

Preeclampsia

14.24 (10.7718.82)

12.74 (9.5317.03)

16.34 (12.1222.04)

14.24 (10.4319.45)

9.12 (4.7517.54)

9.38 (4.8418.16)

................................................................................................................................................................................................................................................................................................................................................................................

The models were controlled for maternal age, ethnicity, smoking, diabetes mellitus, twin pregnancies, lack of prenatal care and parity.
a

Women with nontreated hypertension were not included in the analysis; b Women who were treated with atenolol during the third trimester of pregnancy were not included in the analysis; c Women
who were treated with methyldopa during the third trimester of pregnancy were not included in the analysis.

Orbach. Hypertension/antihypertensive drugs in pregnancy/perinatal outcomes. Am J Obstet Gynecol 2013.

which, 18 infants (6.6%) had been exposed to either methyldopa or atenolol

during the first trimester (adjusted OR,
1.30; 95% CI, 0.84 2.01). Exposure to
antihypertensive drugs (atenolol or
methyldopa) during the third trimester
was associated with PTD, LBW, low Apgar score, IUGR, SGA, and preeclampsia
(Tables 2 and 3). When the data were assessed separately, both atenolol and
methyldopa were associated with these
adverse pregnancy outcomes as well
(Tables 2 and 3).
Nontreated hypertension during pregnancy was associated with increased

risks of PTD, SGA and IUGR, but the

risks for PTD and IUGR were lower
than among treated women with hypertension (Table 4).
Treatment of hypertension in early
pregnancy did not improve the outcomes for preeclampsia (adjusted OR,
1.50; 95% CI, 0.90 2.52), SGA (adjusted
OR, 1.34; 95% CI, 0.45 4.00), and PTD
(adjusted OR, 0.85; 95% CI, 0.56 1.30).

C OMMENT
In this large cohort study, we found that
chronic hypertension with or without

treatment during pregnancy is an independent and significant risk factor for

adverse perinatal outcomes such as SGA,
IUGR,andPTDascomparedwithbirthoutcomes among women without chronic hypertension and without exposure to antihypertensive medications.
Although many studies have advocated
that women with severe chronic hypertension during the pregnancy should be
treated medically, it is not clear whether
women with mild-to-moderate chronic
hypertension should be treated medically.11-17 It has been difficult to separate the
outcomes of the chronic hypertension it-

TABLE 4

Comparison of the risk for preterm delivery, small for gestational age, and intrauterine growth restriction
among women without hypertension, women with hypertension who were not treated, and women with
hypertension who were treated with atenolol or methyldopa during the third trimester of pregnancy
Odds ratio (95% confidence interval)
Variable

Preterm delivery

Small for gestational age

Intrauterine growth
restriction

Preeclampsia

Without hypertension

Reference

Reference

Reference

Reference

Nontreated hypertension

1.89 (1.592.25)

2.06 (1.442.95)

2.09 (1.512.89)

7.02 (5.548.89)

Exposure to atenolol or methyldopa during

the third trimester of pregnancy

3.23 (2.574.05)

2.25 (1.293.94)

4.40 (3.026.40)

12.82 (9.5817.14)

................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................

................................................................................................................................................................................................................................................................................................................................................................................

The models were controlled for maternal age, ethnicity, smoking, diabetes mellitus, twin pregnancies, lack of prenatal care and parity.
Orbach. Hypertension/antihypertensive drugs in pregnancy/perinatal outcomes. Am J Obstet Gynecol 2013.

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self from the potential adverse effects of
the medications that are used. Several
studies have shown that chronic hypertension in pregnancy is associated with
fetal complications such as SGA, PTD,
IUGR, and fetal death4-6; our findings
corroborate those results. Studies have
also shown that women with chronic hypertension that is treated with atenolol
had higher rates of IUGR and PTD,
which are findings that are also corroborated by results of our study (Table
2).22-25 We found that women with
chronic hypertension who were treated
with methyldopa during the third trimester of pregnancy exhibited higher
rates of SGA and PTD. There were differences in the outcome of PTD and preeclampsia between patients who were
treated with methyldopa and those
treated with atenolol (27% vs 17% and
16% vs 9%, respectively), although exposure to atenolol during the third trimester was associated more with SGA
compared with methyldopa (5.6% vs
2.4%). Methyldopa has been used in
many institutions as the drug of choice
for gestational hypertension; therefore,
it is unlikely that women with more severe hypertension were treated with
methyldopa, as opposed to atenolol.
These observations should be further
investigated.
No statistical difference was found
when early treatment in early pregnancy
was compared with treatment in late
pregnancy, which might be because their
hypertension was pregnancy-induced
and started in late pregnancy.
In our population, women with chronic
hypertension who were treated with either atenolol or methyldopa or both
had higher rates of LBW, SGA, PTD,
and IUGR, even after adjustment for
maternal age, ethnicity, smoking, diabetes mellitus, twin pregnancy, lack of
prenatal care, and parity. Adjustment
for confounders can address their
effects on the outcomes but cannot
differentiate between the effects of
the antihypertensive drugs and the hypertension effects on the outcomes.
Confounding by indication (in this
case, hypertension) cannot be adjusted
in the model and should be recognized
as a limitation. However, because we

had a large group of women with hypertension who were not treated with
medications, we could show that most
of the adverse outcomes occurred even
without the drugs. Our study is unique
in having a large cohort of women with
hypertension who were not treated
pharmacologically during the index
pregnancy, which provided a rare opportunity to separate the effect of the
medications from those of the medical
condition. Because we had no data
about the severity of the hypertension,
we assumed that the groups who were
treated by atenolol or methyldopa or
both had experienced more severe hypertension than did the group of
women with hypertension who were
not treated. This may explain the
higher rates of complications such as
LBW or SGA, PTD and IUGR among
the treated women and support the argument that adverse pregnancy outcomes such as LBW, SGA, PTD, and
IUGR in women with chronic hypertension mainly are due to the adverse
effects of the hypertension itself and
not of the medications. Moreover, the
fact that the group of women who were
treated with atenolol and the group of
women who were treated with methyldopa had both shown higher rates of
LBW, SGA, PTD, and IUGR, although
the mechanism of action of the 2 drugs
are completely different, further supports the argument that adverse pregnancy outcomes in women with
chronic hypertension mainly are due
to the effect of the hypertension itself
and not these medications.
In conclusion, with the use of a population-based and relatively large cohort that
separated the role of hypertension from
that of the medications that were used, our
study supports the major adverse effects of
hypertension itself on pregnancy outcome,
rather than atenolol and methyldopa. f

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