Gestational Exposure to Antidepressants and Neurodevelopmental Disorders in Offspring

Untreated depression may adversely affect pregnancy and offspring outcomes through several mechanisms; on the flip side, antidepressants used to treat depression may cross the placenta and affect the developing fetus and its brain. This article examines the research literature on gestational exposure to antidepressants and the risk of neurodevelopmental disorders (NDDs) in offspring. Two recent meta-analyses and 3 subsequently published observational studies, including 1 Asian study, are reviewed with especial focus on autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Despite limitations of the literature, some conclusions can reasonably be drawn. In unadjusted analyses, which assist an understanding of real world risks, gestational exposure to antidepressant drugs is associated with an up to doubled risk of ASD and ADHD. However, in adjusted analyses, which assist an understanding of cause-effect relationships but not real world risks, the risks substantially attenuate and may lose statistical significance. The risks also lose statistical significance in analyses that address confounding by indication by comparing antidepressant-exposed and -unexposed pregnancies in women with psychiatric disorders. The likelihood of confounding by parental genes, parental environment, and parental health-related variables is suggested by findings that antidepressants remain significantly associated with NDDs when the exposure period is outside the pregnancy window (such as before or after but not during pregnancy) or when fathers are exposed to antidepressants during pregnancy. Finally, discordant sibling pair analyses suggest that whether or not a child develops an NDD is related to whether or not its sib has an NDD rather than whether or not the child was exposed to an antidepressant in utero. Discussion points are suggested for the shared decision-making process when counseling women about NDD risks associated with gestational exposure to antidepressant drugs. Take-home messages are summarized.