- Lars Henning Pedersen, research assistant1, visiting scholar 2,
- Tine Brink Henriksen, consultant3,
- Mogens Vestergaard, general practitioner and associate professor4,
- Jørn Olsen, professor and chair2,
- Bodil Hammer Bech, associate professor1
- 1Department of Epidemiology, Institute of Public Health, Aarhus University, Bartolin Allé 2, DK-8000 Aarhus, Denmark
- 2UCLA School of Public Health, Department of Epidemiology, 650 Charles E Young Drive South, Los Angeles, CA 90095-1772, USA
- 3Department of Paediatrics, Aarhus University Hospital, DK-8200 Aarhus, Denmark
- 4Department of General Practice, Institute of Public Health, Aarhus University, Bartolin Allé 2, DK-8000 Aarhus, Denmark
- Correspondence to: Lars Henning Pedersen, Department of Epidemiology, Institute of Public Health, Aarhus University, Bartolins Allé 2, 8000 Aarhus C, Denmark
- Accepted 6 June 2009
Objective To investigate any association between selective serotonin reuptake inhibitors (SSRIs) taken during pregnancy and congenital major malformations.
Design Population based cohort study.
Participants 493 113 children born in Denmark, 1996-2003.
Main outcome measure Major malformations categorised according to Eurocat (European Surveillance of Congenital Anomalies) with additional diagnostic grouping of heart defects. Nationwide registers on medical redemptions (filled prescriptions), delivery, and hospital diagnosis provided information on mothers and newborns. Follow-up data available to December 2005.
Results Redemptions for SSRIs were not associated with major malformations overall but were associated with septal heart defects (odds ratio 1.99, 95% confidence interval 1.13 to 3.53). For individual SSRIs, the odds ratio for septal heart defects was 3.25 (1.21 to 8.75) for sertraline, 2.52 (1.04 to 6.10) for citalopram, and 1.34 (0.33 to 5.41) for fluoxetine. Redemptions for more than one type of SSRI were associated with septal heart defects (4.70, 1.74 to 12.7)). The absolute increase in the prevalence of malformations was 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 one type of SSRI.
Conclusion There is an increased prevalence of septal heart defects among children whose mothers were prescribed an SSRI in early pregnancy, particularly sertraline and citalopram. The largest association was found for children of women who redeemed prescriptions for more than one type of SSRI.
Contributors: LHP, TBH, MV, JO, and BHB were responsible for study concept and design, analysis and interpretation of data, drafting the manuscript and revising it for important intellectual content, and study supervision. LHP, JO, and BHB acquired the data. HP, TBH, and JO obtained funding. LHP and BHB analysed the data. LHP, JO, and BHB gave administrative, technical, or material support. LHP is guarantor.
Funding: This work was funded by a grant from the Lundbeck Foundation (grant No 95092485, sted 2214), an independent foundation supported by the pharmaceutical company Lundbeck, and has received support from the National Danish Research Foundation, the University of Aarhus, the Danish Society of Obstetrics and Gynaecology, the Ville Heise Foundation, and the Rosalie Petersen Foundation. Part of the work was done during LHP’s employment at the Centre for Clinical Pharmacology, University Hospital of Aarhus, Aarhus, Denmark. JO has received grants from the Lundbeck Foundation.
Role of the sponsor: The Lundbeck Foundation had no role in the design and conduct of the study; the collection, analysis, interpretation of the data; or the preparation, review, or approval of the manuscript.
Competing interests: None declared.
Ethical approval: The study was conducted in accordance with the rules of the Danish Data Protection Board and with “Good Epidemiological Practice.”25 Patients’ data were anonymised. Part of the study was done at University of California, Los Angeles, and the study has been subject to approval by the UCLA Institutional Review Board (IRB #G06-04-004-01).
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