Antidepressant exposure during pregnancy and risk of autism in the offspring, 1: Meta-review of meta-analyses

Abstract

There are no randomized controlled trials of antidepressant drugs to treat depression, or to prevent relapse into depression, during pregnancy; therefore, the safety of antidepressant drug exposure during pregnancy is based on evidence from case-control or cohort studies. Many of these observational studies, during the past decade, examined the risk of autism spectrum disorder (ASD) in exposed offspring. Different studies using different methods and examining different periods of antidepressant exposure before and during pregnancy obtained different results. Studies with adverse outcomes were highlighted in the mass media, whereas those with reassuring outcomes were mostly ignored. Meta-analyses were conducted to reconcile the findings of the different studies and determine the magnitude of the effect size. In the last year or so, at least 6 such meta-analyses examined the effects of antidepressant exposure during pregnancy on the risk of ASD in the offspring. The meta-analyses set different study selection criteria and employed different methods of analysis to address different objectives. The findings across meta-analyses have been reasonably consistent. Antidepressant exposure during pregnancy is associated with an increased risk of ASD in the offspring. The risk is decreased after adjusting for confounding variables and is mostly no longer statistically significant after adjusting for maternal mental illness. Additionally, antidepressant exposure is associated with an increased risk of ASD in the offspring even when exposure is limited to the preconception period, when the drugs cannot have a physiological effect on the fetus. These findings suggest that maternal mental illness is an important determinant of the risk of ASD associated with antidepressant exposure during pregnancy.