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Original Investigation
April 18, 2017

Association Between Serotonergic Antidepressant Use During Pregnancy and Autism Spectrum Disorder in Children

Author Affiliations
  • 1Women’s College Research Institute, Women’s College Hospital, Toronto, Ontario, Canada
  • 2Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
  • 3Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
  • 4Department of Obstetrics and Gynaecology, St Michael’s Hospital, Toronto, Ontario, Canada
  • 5Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  • 6Centre for Addiction and Mental Health, Toronto, Ontario, Canada
  • 7Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
JAMA. 2017;317(15):1544-1552. doi:10.1001/jama.2017.3415
Key Points

Question  What is the risk of autism spectrum disorder in children with in utero exposure to a serotonergic antidepressant compared with unexposed children?

Findings  In this retrospective cohort study of 35 906 singleton births, there was not a statistically significant association between exposure to serotonergic antidepressants compared with no exposure in inverse probability of treatment-weighted analyses or when comparing exposed with unexposed siblings.

Meaning  Maternal use of serotonergic antidepressants during pregnancy compared with no use was not associated with autism spectrum disorder in their children. Although a causal relationship cannot be ruled out, the previously observed association may be explained by other factors.

Abstract

Importance  Previous observations of a higher risk of child autism spectrum disorder with serotonergic antidepressant exposure during pregnancy may have been confounded.

Objective  To evaluate the association between serotonergic antidepressant exposure during pregnancy and child autism spectrum disorder.

Design, Setting, and Participants  Retrospective cohort study. Health administrative data sets were used to study children born to mothers who were receiving public prescription drug coverage during pregnancy in Ontario, Canada, from 2002-2010, reflecting 4.2% of births. Children were followed up until March 31, 2014.

Exposures  Serotonergic antidepressant exposure was defined as 2 or more consecutive maternal prescriptions for a selective serotonin or serotonin-norepinephrine reuptake inhibitor between conception and delivery.

Main Outcomes and Measures  Child autism spectrum disorder identified after the age of 2 years. Exposure group differences were addressed by inverse probability of treatment weighting based on derived high-dimensional propensity scores (computerized algorithm used to select a large number of potential confounders) and by comparing exposed children with unexposed siblings.

Results  There were 35 906 singleton births at a mean gestational age of 38.7 weeks (50.4% were male, mean maternal age was 26.7 years, and mean duration of follow-up was 4.95 years). In the 2837 pregnancies (7.9%) exposed to antidepressants, 2.0% (95% CI, 1.6%-2.6%) of children were diagnosed with autism spectrum disorder. The incidence of autism spectrum disorder was 4.51 per 1000 person-years among children exposed to antidepressants vs 2.03 per 1000 person-years among unexposed children (between-group difference, 2.48 [95% CI, 2.33-2.62] per 1000 person-years; hazard ratio [HR], 2.16 [95% CI, 1.64-2.86]; adjusted HR, 1.59 [95% CI, 1.17-2.17]). After inverse probability of treatment weighting based on the high-dimensional propensity score, the association was not significant (HR, 1.61 [95% CI, 0.997-2.59]). The association was also not significant when exposed children were compared with unexposed siblings (incidence of autism spectrum disorder was 3.40 per 1000 person-years vs 2.05 per 1000 person-years, respectively; adjusted HR, 1.60 [95% CI, 0.69-3.74]).

Conclusions and Relevance  In children born to mothers receiving public drug coverage in Ontario, Canada, in utero serotonergic antidepressant exposure compared with no exposure was not associated with autism spectrum disorder in the child. Although a causal relationship cannot be ruled out, the previously observed association may be explained by other factors.

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