This article has a correction

Please see: BMJ Open 2013;3

BMJ Open 2:e001148 doi:10.1136/bmjopen-2012-001148
  • Pharmacology and therapeutics
    • Research

Exposure to selective serotonin reuptake inhibitors and the risk of congenital malformations: a nationwide cohort study

  1. Henrik Enghusen Poulsen1,2,4
  1. 1Laboratory of Clinical Pharmacology, Rigshospitalet, Copenhagen, Denmark
  2. 2Department of Clinical Pharmacology, Bispebjerg Hospital, Copenhagen, Denmark
  3. 3Department of Cardiology, Gentofte Hospital, Copenhagen, Denmark
  4. 4Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
  1. Correspondence to Espen Jimenez-Solem; espen.jimenez.solem{at}
  • Received 11 March 2012
  • Accepted 11 May 2012
  • Published 18 June 2012


Objectives To analyse the relation between selective serotonin reuptake inhibitor (SSRI) use and major congenital malformations, with focus on malformations of the heart.

Design Register-based retrospective nationwide cohort study, using the Danish Medical Birth Registry.

Setting Denmark.

Participants Pregnant women in Denmark between 1997 and 2009 and their offspring.

Primary outcome measures For each SSRI, ORs for major congenital malformations were estimated using multivariable logistic regression models for women exposed to an SSRI during the first trimester and for women with paused exposure during pregnancy.

Results The authors identified 848 786 pregnancies; 4183 were exposed to an SSRI throughout the first trimester and 806 pregnancies paused exposure during pregnancy. Risks of congenital malformations of the heart were similar for pregnancies exposed to an SSRI throughout the first trimester, adjusted OR 2.01 (95% CI 1.60 to 2.53), and for pregnancies with paused SSRI treatment during pregnancy, adjusted OR 1.85 (95% CI 1.07 to 3.20), p value for difference: 0.94. The authors found similar increased risks of specific congenital malformations of the heart for the individual SSRIs. Furthermore, the authors found no association with dosage.

Conclusions The apparent association between SSRI use and congenital malformations of the heart may be confounded by indications. The moderate absolute risk increase combined with uncertainty for causality still requires the risk versus benefit to be evaluated in each individual case.


  • To cite: Jimenez-Solem E, Andersen JT, Petersen M, et al. Exposure to selective serotonin reuptake inhibitors and the risk of congenital malformations: a nationwide cohort study. BMJ Open 2012;2:e001148. doi:10.1136/bmjopen-2012-001148

  • Contributors EJ-S, JTA and HEP conceptualised the study and MP, KB, JKJ, SA, GHG and CT-P assisted with the study design. EJ-S preformed the analyses and JTA, MP, KB, CT-P and HEP assisted in the interpretation. EJ-S, JTA, MP, KB, JKJ, SA, GHG, CT-P and HEP wrote and revised the article, as well as designed figures. All authors approved the final version to be published.

  • Funding The research project was partially sponsored by the Capital Region of Copenhagen and the Danish Agency for Science, Technology and Innovation. Coverage of PhD enrolment fees.

  • Competing interests All authors 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 3 years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethics approval The present study has been approved by the Danish Data Protection Agency (No. 2008-41-2517). Retrospective register studies do not require ethical permission in Denmark.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data were available.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: and

blog comments powered by Disqus