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Selective serotonin reuptake inhibitors in pregnancy and congenital malformations: population based cohort study

BMJ 2009; 339 doi: (Published 23 September 2009) Cite this as: BMJ 2009;339:b3569

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SSRIs and cardiac malformations

We read with interest the article by Pedersen et al (1) published in
the BMJ on selective serotonin reuptake inhibitors (SSRIs) in pregnancy
and congenital malformations. In a study using data from Danish nationwide
registries, the authors followed the standard approach of previous
population-based studies on this topic. They arrived at the same
conclusion of a 2-fold increased risk for septal heart defects after first
trimester exposure to SSRI's (odds ratio 1.99, 95 % confidence interval
1.13 - 3.53). However, contrary to other studies they found an increased
prevalence of heart defects following exposure to citalopram or sertraline
but not to paroxetine or fluoxetine. The greatest risk was observed for
infants exposed in-utero to more than one type of SSRI.
We have recently published our data on first trimester exposure to SSRI
and cardiac malformations (2). Our aim was to compare the rate of non-
syndromic, non-chromosomal congenital heart malformations in SSRI's
exposed newborns to that of unexposed controls. We used a unique screening
approach that included an examination by a pediatric cardiologist and
echocardiography for every newborn with a persistent cardiac murmur (even
mild) on the second or third day of life. This methodology has not been
reported in any of the previous studies on SSRI exposure. Non-syndromic
congenital heart defects were identified by echocardiography in 3.4% of
exposed newborns and in 1.6% in non-exposed babies (relative risk, 2.17,
95% confidence interval, 1.07 – 4.39). All cardiac defects in the study
group were mild: ventricular septal defect, bicuspid aortic valve and
right superior vena cava to coronary sinus. Although our sample size was
too small for analysis of specific drugs, it is interesting to remark that
all four SSRI's (paroxetine, fluoxetine, citalopram and sertraline) were
involved in the exposed newborns with heart defects. On the basis of our
data and clinical experience, it seems appropriate to reassure the women
who require treatment with SSRI's during early pregnancy that the risk is
small and that possible heart malformations are usually mild and often
resolved spontaneously. Early pregnancy monitoring, a late-targeted
ultrasound and fetal echocardiography at 22-23 weeks gestation are
advised. Further larger studies using our unique approach or other
methods are still needed.


1.Pedersen LH, Henriksen TB, Vestergaard M, Olsen J, Bech BH.
Selective serotonin reuptake inhibitbors in pregnancy and congenital
malformations: population based cohort study. BMJ 2009;339:b3569.

2.Paul Merlob, Einat Birk, Lea Sirota, Nechama Linder, Michael
Berant, Bracha Stahl, Gil Klinger. Are Selective Serotonin Reuptake
Inhibitors Cardiac Teratogens? Echocardiographic Screening of Newborns
with Persistent Heart Murmur – Birth Defects Res Part A 2009 Aug 18.
[Epub ahead of print]

Competing interests:
None declared

Competing interests: No competing interests

01 October 2009
Gil Klinger
Deputy Director, NICU, Schneider Children's Medical Center of Israel
Paul Merlob
14 Kaplan St, Petah Tiqva ,49202, Israel