Use of selective serotonin-reuptake inhibitors during pregnancy and the risk of clubfoot

Abstract

Background: Selective serotonin-reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants. Previous studies have suggested that SSRIs may increase the risk of birth defects, including clubfoot. Using data from a population-based case-control study, we evaluated whether SSRI use increased the risk of clubfoot.

Methods: Mothers were interviewed within 1 year after delivery about sociodemographic factors, pregnancy events, and exposures. They were specifically asked if they experienced depression or anxiety or if they took any of the following SSRIs: citalopram, escitalopram, fluvoxamine, paroxetine, sertraline, or fluoxetine. We used logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: We included a total of 622 clubfoot cases and 2002 nonmalformed controls born between 2006 and 2011 in Massachusetts, New York, and North Carolina. For the 2nd or 3rd lunar month of pregnancy (the relevant gestational period), SSRI use for a period of more than 30 days was higher in case mothers (5%) than control mothers (3%). After adjustment for maternal smoking and body mass index, the OR for any SSRI use and clubfoot was 1.8 (95% CI = 1.1-2.8). When individual SSRIs were examined, ORs were elevated for sertraline (1.6 [0.8-3.2]), paroxetine (9.2 [0.7-484.6]), and escitalopram (2.9 [1.1-7.2]).

Conclusion: Our data suggest an increased risk of clubfoot occurrence in relation to SSRI use. Drug-specific risks varied widely, and some estimates were unstable.

Conflict of interest statement

Conflicts of interest: MMW holds consultancy contracts with Amgen, Abbott, and UCB; no financial relationships with any organizations that might have an interest in this work; and no other relationships or activities that could appear to have influenced these analyses. AAM and CL received GlaxoSmithKline support for an analysis of bupropion in relation to cardiac defects. AAM serves as a member of advisory committees for Biogen-Idec’s pregnancy registries for biologics used to treat multiple sclerosis. MMY states no known conflicts of interest.

Figures

Figure 1

Frequency of selective serotonin reuptake inhibitor use among control mothers, Massachusetts, New York, and North Carolina, 2006 – 2011. The denominator for each lunar month includes only control mothers who were pregnant in that lunar month

Figure 2

Frequency of selective serotonin reuptake inhibitor use in the 2nd and 3rd lunar months among control mothers by year of last menstrual period, Massachusetts, New York, and North Carolina, 2006 – 2011.