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Pediatrics Research 1 Credit CME

Antidepressant Use During Pregnancy and the Risk of Autism Spectrum Disorder in Children

Original Investigation
Educational Objective
To examine the risk of autism spectrum disorder in children associated with antidepressant use during pregnancy according to trimester of exposure and taking into account maternal depression.

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Abstract

Importance  The association between the use of antidepressants during gestation and the risk of autism spectrum disorder (ASD) in children is still controversial. The etiology of ASD remains unclear, although studies have implicated genetic predispositions, environmental risk factors, and maternal depression.

Objective  To examine the risk of ASD in children associated with antidepressant use during pregnancy according to trimester of exposure and taking into account maternal depression.

Design, Setting, and Participants  We conducted a register-based study of an ongoing population-based cohort, the Québec Pregnancy/Children Cohort, which includes data on all pregnancies and children in Québec from January 1, 1998, to December 31, 2009. A total of 145 456 singleton full-term infants born alive and whose mothers were covered by the Régie de l’assurance maladie du Québec drug plan for at least 12 months before and during pregnancy were included. Data analysis was conducted from October 1, 2014, to June 30, 2015.

Exposures  Antidepressant exposure during pregnancy was defined according to trimester and specific antidepressant classes.

Main Outcomes and Measures  Children with ASD were defined as those with at least 1 diagnosis of ASD between date of birth and last date of follow-up. Cox proportional hazards regression models were used to estimate crude and adjusted hazard ratios with 95% CIs.

Results  During 904 035.50 person-years of follow-up, 1054 children (0.7%) were diagnosed with ASD; boys with ASD outnumbered girls by a ratio of about 4:1. The mean (SD) age of children at the end of follow-up was 6.24 (3.19) years. Adjusting for potential confounders, use of antidepressants during the second and/or third trimester was associated with the risk of ASD (31 exposed infants; adjusted hazard ratio, 1.87; 95% CI, 1.15-3.04). Use of selective serotonin reuptake inhibitors during the second and/or third trimester was significantly associated with an increased risk of ASD (22 exposed infants; adjusted hazard ratio, 2.17; 95% CI, 1.20-3.93). The risk was persistent even after taking into account maternal history of depression (29 exposed infants; adjusted hazard ratio, 1.75; 95% CI, 1.03-2.97).

Conclusions and Relevance  Use of antidepressants, specifically selective serotonin reuptake inhibitors, during the second and/or third trimester increases the risk of ASD in children, even after considering maternal depression. Further research is needed to specifically assess the risk of ASD associated with antidepressant types and dosages during pregnancy.

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Article Information

Accepted for Publication: September 17, 2015.

Corresponding Author: Anick Bérard, PhD, Faculty of Pharmacy, University of Montréal, 3175, Côte-Sainte-Catherine, Montréal, QC, H3T 1C5, Canada (anick.berard@umontreal.ca).

Published Online: December 14, 2015. doi:10.1001/jamapediatrics.2015.3356.

Author Contributions: Dr Bérard and Ms Boukhris had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Boukhris, Sheehy, Bérard.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Boukhris, Bérard.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Boukhris, Sheehy,

Obtained funding: Bérard.

Administrative, technical, or material support: Bérard.

Study supervision: Bérard.

Conflict of Interest Disclosures: Dr Bérard reported serving as a consultant for plaintiffs in the litigations involving antidepressants and birth defects. No other disclosures were reported.

Funding/Support: This study was supported by the Canadian Institutes of Health Research and the Québec Training Network in Perinatal Research.

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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