Prenatal selective serotonin reuptake inhibitor use and the risk of autism spectrum disorder in children: A systematic review and meta-analysis

•Substantial controversy exists whether prenatal SSRI use is associated with autism spectrum disorder (ASD) in children.•We aimed to investigate this controversy through a systematic review and meta-analysis of observational studies.•Meta-analysis of case-control studies suggested a significance for SSRI exposures during the 1st, 2nd trimester and anytime during pregnancy.•The significance with preconceptional exposure to SSRIs and negative/inconsistent findings among cohort studies weakened this association.•Confounding by indication still cannot be ruled out.

ObjectiveTo determine whether an up-to-date systematic review and meta-analysis of observational studies would support the previously suggested associations regarding prenatal selective serotonin reuptake inhibitor (SSRI) use and the risk for autism spectrum disorders (ASD) in children.MethodsPubMed/MEDLINE, Cochrane Central Register of Controlled Trials and Reprotox databases were searched; observational studies with an exposed and unexposed group were included.ResultsThe meta-analysis of case-control studies demonstrated a significantly increased risk of ASD in the children whose mothers were prenatally exposed to SSRIs during different exposure time windows (except third trimester). The qualitative review of the cohort studies suggested inconsistent findings.ConclusionsThe significant association between preconception-only SSRI exposure and ASD in the children and negative/inconsistent findings among cohort studies weaken the significant associations detected in this meta-analysis. We suggest that confounding by indication still cannot be ruled out regarding prenatal SSRI exposure and ASD in children.