Specific SSRIs and birth defects: bayesian analysis to interpret new data in the context of previous reportsBMJ 2015; 351 doi: https://doi.org/10.1136/bmj.h3190 (Published 08 July 2015) Cite this as: BMJ 2015;351:h3190
- Jennita Reefhuis, research health scientist1,
- Owen Devine, senior statistician1,
- Jan M Friedman, professor2,
- Carol Louik, epidemiologist3,
- Margaret A Honein, senior research health scientist1
- on behalf of the National Birth Defects Prevention Study
- 1National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, USA
- 2Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- 3Slone Epidemiology Center at Boston University, Boston, MA, USA
- Correspondence to: J Reefhuis
- Accepted 29 May 2015
Objective To follow up on previously reported associations between periconceptional use of selective serotonin reuptake inhibitors (SSRIs) and specific birth defects using an expanded dataset from the National Birth Defects Prevention Study.
Design Bayesian analysis combining results from independent published analyses with data from a multicenter population based case-control study of birth defects.
Setting 10 centers in the United States.
Participants 17 952 mothers of infants with birth defects and 9857 mothers of infants without birth defects, identified through birth certificates or birth hospitals, with estimated dates of delivery between 1997 and 2009.
Exposures Citalopram, escitalopram, fluoxetine, paroxetine, or sertraline use in the month before through the third month of pregnancy. Posterior odds ratio estimates were adjusted to account for maternal race/ethnicity, education, smoking, and prepregnancy obesity.
Main outcome measure 14 birth defects categories that had associations with SSRIs reported in the literature.
Results Sertraline was the most commonly reported SSRI, but none of the five previously reported birth defects associations with sertraline was confirmed. For nine previously reported associations between maternal SSRI use and birth defect in infants, findings were consistent with no association. High posterior odds ratios excluding the null value were observed for five birth defects with paroxetine (anencephaly 3.2, 95% credible interval 1.6 to 6.2; atrial septal defects 1.8, 1.1 to 3.0; right ventricular outflow tract obstruction defects 2.4, 1.4 to 3.9; gastroschisis 2.5, 1.2 to 4.8; and omphalocele 3.5, 1.3 to 8.0) and for two defects with fluoxetine (right ventricular outflow tract obstruction defects 2.0, 1.4 to 3.1 and craniosynostosis 1.9, 1.1 to 3.0).
Conclusions These data provide reassuring evidence for some SSRIs but suggest that some birth defects occur 2-3.5 times more frequently among the infants of women treated with paroxetine or fluoxetine early in pregnancy.
We thank Tiffany Colarusso and Jennifer Lind for their valuable contributions to this paper. Coding of drug information in the National Birth Defects Prevention Study used the Slone Drug Dictionary under license from the Slone Epidemiology Center of Boston University.
Contributors: JR designed the study, did the frequentist data analyses, and wrote the first draft of the manuscript. She is the guarantor. OD performed the bayesian statistical analyses and revised the drafted manuscript. JMF, CL, and MAH provided epidemiological feedback on initial data tables and revised the drafts. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Funding: Data collection was funded by the US Centers for Disease Control and Prevention.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: This study was approved by the institutional review board of the Centers for Disease Control and Prevention and all participating sites.
Data sharing: Previous publications with a subset of this data: Alwan S, Reefhuis J, Rasmussen SA, et al. Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. N Engl J Med 2007;356:2684-92 and Alwan S, Reefhuis J, Rasmussen SA, et al. Patterns of antidepressant medication use among pregnant women in a United States population. J Clin Pharmacol 2011;51:264-70.
Transparency: The leader author (JR) hereby affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
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