Gestational Exposure to Antidepressant Drugs and Neurodevelopment: An Examination of Language, Mathematics, Intelligence, and Other Cognitive Outcomes

During the past decade, nearly a dozen small and large, prospective and retrospective observational studies examined cognitive neurodevelopmental outcomes in childhood after gestational exposure to antidepressant drugs. Many of the studies found that exposure was associated with poorer outcomes on measures of language, cognition, intellectual skills, and academic performance, but, in most instances, the association appeared to be more related to maternal depression during pregnancy and other confounds than to antidepressant use during pregnancy. A large new population-based observational study specifically examined language and mathematics performance in serial, nationally standardized tests. The study found that, in fully adjusted analyses, in children and adolescents aged 9-15 years, a history of gestational exposure to antidepressant drugs was associated with a small (by about 2 out of 100 points) but statistically significantly poorer performance in mathematics but not in language. The findings were consistent though attenuated in a large number of important and appropriate sensitivity analyses, some of which adjusted for confounding in additional ways. The body of literature reviewed suggests that prenatal antidepressant exposure is indeed associated with cognitive neurodevelopmental deficits and that the deficits are attenuated or eliminated by adjustment for maternal depression and other confounds. It is suggested that the deficits that remain despite adjustment may be due to residual confounding from unmeasured behavioral and internal environment variables associated with untreated maternal depression. Thus, prenatal antidepressant exposure may merely be a marker rather than the cause of cognitive neurodevelopmental deficits. Whereas the literature in the field does not drive a case for withholding antidepressants from depressed pregnant women, decision-making must remain a shared process.

Automated summary

Over the past decade, numerous observational studies have examined the cognitive neurodevelopmental outcomes in children exposed to antidepressant drugs during pregnancy. While some studies found associations between exposure and poorer outcomes in language, cognition, intellectual skills, and academic performance, these associations were often related to maternal depression during pregnancy and other confounding factors, rather than the use of antidepressants. A recent large-scale population-based study specifically focused on language and mathematics performance and found that gestational exposure to antidepressant drugs was associated with a small, statistically significant decline in mathematics performance but not in language. After adjusting for confounding factors, the remaining deficits may be attributed to unmeasured variables associated with untreated maternal depression. This suggests that prenatal antidepressant exposure may serve as a marker rather than the direct cause of cognitive neurodevelopmental deficits. While the literature does not support withholding antidepressants from depressed pregnant women, decision-making should be a shared process.