Association between serotonergic antidepressant use during pregnancy and autism spectrum disorder in children

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

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

Design, Setting, and Participants — This retrospective cohort study used health administrative datasets to study children born to mothers receiving public prescription drug coverage during pregnancy in Ontario, 2002-2010—reflecting 4.2% of births. We followed children to March 31, 2014.

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

Main Outcomes and Measures — Autism spectrum disorder arising after age 2 years. Exposure group differences were addressed by inverse probability of treatment weighting based on derived high-dimensional propensity scores and by comparing exposed children to unexposed siblings.

Results — There were 35906 singleton births, at a mean gestational age of 38.7 weeks; 50.4% were male, and mean maternal age was 26.7 years. In the 2837 (7.9%) pregnancies exposed to antidepressants, 2.0% of children (95% CI 1.6-2.6) were diagnosed with autism spectrum disorder by the end of follow-up. The incidence of autism spectrum disorder was 4.51 vs. 2.03 per 1000 person-years among exposed versus unexposed children—a difference of 2.48 per 1000 person-years (95% CI 2.33-2.62) (hazard ratio, HR, 2.16, 95% CI 1.64-2.86; adjusted HR 1.59, 95% CI 1.17-2.17). With inverse probability of treatment weighting based on the high-dimensional propensity score, the association was non-significant (HR 1.61, 95% CI 0.997-2.59). The association was also non-significant when exposed children were compared to unexposed siblings (incidence: 3.40 to 2.05 per 1000 person-years, adjusted HR 1.60, 95% CI 0.69-3.74).

Conclusions and Relevance — In children born to mothers receiving public drug coverage in Ontario, 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.