Annual Research Review: Maternal antidepressant use during pregnancy and offspring neurodevelopmental problems - a critical review and recommendations for future research.

Children of women treated with antidepressants during pregnancy are more likely to develop neurodevelopmental problems than are unexposed children. Associations between prenatal antidepressant exposure and neurodevelopmental problems could reflect a causal effect or could be partially or fully explained by other factors that differ between exposed and unexposed offspring, including having mothers with conditions requiring antidepressant treatment (e.g. depression), environmental risk factors, and/or genetic risk factors shared across disorders. This translational review aims to provide a brief overview of findings from rodent experiments and critically evaluate observational studies in humans to assess the extent to which associations between prenatal antidepressant exposure and neurodevelopmental problems are due to causal mechanisms versus other influences. We focus our review on two important neurodevelopmental outcomes - autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). In general, rodent studies have reported adverse effects of perinatal antidepressant exposure on neurodevelopment. Between-species differences raise questions about the generalizability of these findings to humans. Indeed, converging evidence from studies using multiple designs and approaches suggest that observed associations between prenatal antidepressant exposure and neurodevelopmental problems in humans are largely due to confounding factors. We also provide specific recommendations for future research. Animal research should explicitly evaluate the impact of timing of exposure and dosage of medications, as well as better map outcome measures in rodents to human neurodevelopmental problems. Observational studies should investigate specific confounding factors, specific antidepressant drugs and classes, the potential impact of timing of exposure, and a wider range of other potential offspring outcomes. The findings summarized in this review may help women and their doctors make informed decisions about antidepressant use during pregnancy by providing reassurance that use of these medications during pregnancy is unlikely to substantially increase the risk of ASD and ADHD.