Small but Significant Risk for Heart Defects Linked to SSRI Use During Pregnancy

Caroline Cassels

October 15, 2009

September 25, 2009 — Children born to women taking selective serotonin reuptake inhibitors (SSRIs) in early pregnancy have a small but significant increased risk for septal heart defects, new research shows.

A large, population-based cohort study conducted by researchers at Aarhus University in Denmark and published online September 25 in BMJ shows overall monotherapy with an SSRI during pregnancy was associated with an odds ratio of 1.99 (95% confidence interval [CI], 1.13 – 3.53) for septal heart malformations in children.

However, for individual SSRIs the risk for septal heart defects varied.

Odds Ratios for Septal Heart Defects for Individual SSRIs

SSRI Odds Ratio 95% CI
Sertraline 3.25 1.21 – 8.75
Citalopram 2.52 1.04 – 6.10
Fluoxetine 1.34 0.33 – 5.41

In addition, children of women who were prescribed more than 1 type of SSRI during pregnancy had a 4-fold increased risk for septal heart defects — a finding that suggests that simultaneous use of different SSRIs or a change in type of SSRI during early pregnancy may be problematic.

Putting these figures into context, the authors note that the absolute differences in heart defects were low. For example, the prevalence of septal heart defects was 0.5% (2315/493,113) among unexposed children, 0.9% (12/1370) among children whose mothers were prescribed any SSRI, and 2.1% (4/193) among children whose mothers were prescribed more than 1 type of SSRI, the investigators report.

SSRI Use in Pregnancy Common, Increasing

According to the article, depression affects up to 20% of pregnant women, and use of SSRIs during pregnancy is common and increasing. However, the teratogenic effects of specific SSRIs are unconfirmed.

Recent studies have indicated an increased prevalence of various birth defects associated with SSRI use in pregnancy — most consistently, heart defects. This suspected risk led to the 2005 warning by the US Food and Drug Administration related to the use of paroxetine during pregnancy.

To investigate the association between SSRIs taken in the first trimester of pregnancy and major malformations, the researchers used data from 4 Danish nationwide registries in 496,881 singleton children born between 1996 and 2003.

In addition, the investigators analyzed data on filled prescriptions, delivery, and hospitals diagnosis on mothers and newborns. Exposure to an SSRI was defined as 28 days before to 112 days after the beginning of gestation.

The study's main outcome measure was major malformations categorized according to the European Surveillance of Congenital Anomalies.

The investigators found there was no significant increased prevalence of major malformations or noncardiac malformations among exposed children vs nonexposed children.

However, there was an increased prevalence of septal heart defects for children of women who used sertraline and citalopram, but not fluoxetine. In addition, children whose mothers had filled prescriptions for more than 1 type of SSRI in the exposure window had a significantly increased risk for septal heart defects.

"Our results suggest a class effect of the SSRI on heart defects, and the equivocal results from existing studies could represent differences in doses or study population. The associations, if causal, represent limited risk of an exposed child having congenital heart defects. Future studies need much larger sample sizes, preferably with sufficient power to further investigate potential associations with more severe malformations," the authors write.

Weighing Risks and Benefits

In an accompanying editorial, Christina Chambers, PhD, associate professor of pediatrics, University of California–San Diego, writes that the small risk for harm shown in this study must be weighed against the risk of suboptimal or no treatment.

Dr. Chambers notes that "if an increased risk for major congenital malformations does exist, this study and others suggest that the absolute risk for the individual pregnant women is very low. Furthermore, each of the more commonly used drugs in this class has been implicated in at least 1 study so it is difficult to conclude that 1 SSRI is 'safer' than another."

In the meantime, Dr. Chambers recommends that women and their physicians look to the recently published guidelines from the American College of Obstetrics and Gynecology and the American Psychiatric Association to help guide their treatment decisions.

These recommendations state that women with major depressive disorder who are contemplating pregnancy or who are currently pregnant can start or continue taking their medications. For women who prefer to avoid or discontinue drugs, psychotherapy can also be an effective treatment option. However, Dr. Chambers notes that its efficacy is often determined by an individual's psychiatric history.

Dr. Chambers added that more research, with larger numbers of participants, is needed before any definitive conclusions can be drawn about SSRI use during pregnancy.

"Although research about SSRIs and pregnancy outcomes is plentiful, it does not necessarily provide definitive answers for clinical practice. Clinicians and patients need to balance the small risks associated with SSRIs against those associated with undertreatment or no treatment," she writes.

BMJ. Published online September 25, 2009.

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