The Association Between Antenatal Exposure to Selective Serotonin Reuptake Inhibitors and Autism: A Systematic Review and Meta-Analysis

Objective: This systematic review and meta-analysis examines the relationship between antenatal selective serotonin reuptake inhibitor (SSRI) exposure and child autism, with specific attention to maternal mental illness (MMI) as a potential confounding factor.

Data Sources: We searched MEDLINE, Embase, PsycINFO, and CINAHL from database inception to January 28, 2016.

Study Selection: Keywords included terms for SSRIs, pregnancy, and autism. We included published, peer-reviewed articles written in English.

Data Extraction: Two reviewers used standardized instruments for data extraction and quality assessment. We generated pooled estimates for studies of the same design for SSRI exposure at any time during pregnancy and exposure during the first trimester. Subanalyses were conducted among studies with analyses (1) adjusted for MMI and (2) restricted to MMI.

Results: We included in the meta-analysis 4 case-control studies and 2 cohort studies. In the case-control studies, the adjusted pooled odds ratio (aPOR) values were 1.4 (95% CI, 1.0-2.0) (any) and 1.7 (95% CI, 1.1-2.6) (first trimester). In MMI-adjusted analyses, only first trimester exposure remained statistically significant (aPOR = 1.8; 95% CI, 1.1-3.1). In MMI-restricted analyses, neither exposure period was statistically significant. In the cohort studies, MMI-adjusted relative risk values were 1.5 (95% CI, 0.9-2.7) (any) and 1.4 (95% CI, 1.0-1.9) (first trimester). In MMI-restricted analyses, SSRI exposure at any time during pregnancy was nonsignificant.

Conclusions: It remains unclear whether the association between first trimester SSRI exposure and child autism that was present in the case-control studies even after adjustment for MMI is a true association or a product of residual confounding. Future studies require robust measurement of MMI prior to and during pregnancy.