Share this article on:

Selective Serotonin Reuptake Inhibitors and Risk for Major Congenital Anomalies

Malm, Heli MD, PhD; Artama, Miia MSc, PhD; Gissler, Mika MSocSc, PhD; Ritvanen, Annukka MD

doi: 10.1097/AOG.0b013e318220edcc
Original Research

OBJECTIVE: To estimate the risk of major congenital anomalies after exposure to selective serotonin reuptake inhibitors during pregnancy.

METHODS: A retrospective cohort study based on national population-based registers (years 1996–2006) of births, congenital anomalies, and terminations of pregnancy because of severe fetal anomalies (maintained by National Institute for Health and Welfare, source offspring population n=635,583) and drug reimbursements (Social Insurance Institution) linked by a personal identification number. Offspring exposed to selective serotonin reuptake inhibitors during the first trimester (n=6,976) were compared with unexposed referent offspring.

RESULTS: Overall major congenital anomalies were not more common in selective serotonin reuptake inhibitor-exposed offspring compared with unexposed referent offspring (adjusted odds ratio [OR] 1.08, 95% confidence interval [CI] 0.96–1.22). Fluoxetine was associated with an increased risk of isolated ventricular septal defects (adjusted OR 2.03, 95% CI 1.28–3.21) and paroxetine was associated with an increased risk of right ventricular outflow tract defects (adjusted OR 4.68, 95% CI 1.48–14.74). Citalopram use was associated with neural tube defects (adjusted OR 2.46, 95% CI 1.20–5.07). Fetal alcohol spectrum disorders were 10-times more common in the selective serotonin reuptake inhibitor-exposed offspring than in unexposed referent offspring.

CONCLUSION: Fluoxetine use is associated with an increased risk of isolated ventricular septal defects and paroxetine is associated with right ventricular outflow tract defects. The absolute risk for these specific cardiac anomalies is small but should guide clinicians not to consider fluoxetine or paroxetine the first option when prescribing selective serotonin reuptake inhibitors to women planning pregnancy. Special attention should be given to alcohol use in pregnant women using selective serotonin reuptake inhibitors.

LEVEL OF EVIDENCE: II

Fluoxetine use during early pregnancy is associated with an increased risk of ventricular septal defects and paroxetine use with right ventricular outflow tract defects.

From the Teratology Information Service, Helsinki University Central Hospital and HUSLAB, Helsinki, Finland; the Department of Clinical Pharmacology, Helsinki University and Helsinki University Central Hospital, Helsinki, Finland; the National Institute for Health and Welfare, Helsinki, Finland; and the Nordic School of Public Health, Göteborg, Sweden.

Funded by the Social Insurance Institution in Finland, the Finnish Medicines Agency, and the National Institute for Health and Welfare. The study material was derived from the Drugs and Pregnancy project database.

The authors thank the Drugs and Pregnancy study group for their input in building and maintaining the combined database for surveillance and study purposes.

Corresponding author: Heli Malm, Teratology Information Service, HUSLAB, PO Box 790, 00029 HUS, Helsinki, Finland; e-mail heli.malm@hus.fi.

Financial Disclosure The authors did not report any potential conflicts of interest.

© 2011 The American College of Obstetricians and Gynecologists