Several previous studies have suggested that children exposed to antidepressants in utero may be at increased risk for experiencing depression during adolescence.  While this is obviously a reasonable concern, it is difficult to separate out genetic and environmental factors.

Using a rich dataset collected from the Danish national medical registries, a recent study from Rommel and colleagues looks at risk for affective illness up to 18 years of age in children with prenatal exposure to antidepressants.

The study included 42,988 singletons born between 1998 and 2011 who were followed until 2016 (or until death or emigration).  The children were divided into two categories based on maternal antidepressant use in the two years before and during pregnancy: continuation (use before and during pregnancy) or discontinuation (use before but not during pregnancy). 

The primary outcome assessed was the diagnosis of an affective disorder in the child as documented in secondary or tertiary care records and prescription records. Hazard ratios (HR) of affective disorders were estimated using Cox regression models. 

Affective disorders were identified in 1538 of the 42,988 children included in this study. Children whose mothers maintained antidepressants during pregnancy had a small but statistically significant increase in risk of affective disorders (HR=1.20, 95% CI=1.08–1.34), as compared to children whose mothers discontinued antidepressants before pregnancy. 

This study used a novel approach to account for confounding by genetic or shared environmental factors.  They also measured the effect of antidepressant use in the father on risk for affective illness in the child. They observed that the continued use of antidepressants during pregnancy in father was also associated with an increase in risk for affective disorders in the child (HR?=1.29, 95% CI=1.12–1.49), compared to children whose fathers did not continue treatment with an antidepressant during pregnancy.

Because the hazard ratios for affective illness in the children are similar whether the mother or father took the antidepressant during pregnancy, the observed association between antidepressant exposure and increased vulnerability to affective illness in the child is not likely due to intrauterine exposure to the antidepressant.  Rather it is appears that underlying psychopathology in the mother or father – the reason for taking the antidepressant — is responsible for this increased vulnerability.  Whether this association is driven by genetic factors or shared environmental factors (or both), we do not yet know. But we can’t always blame exposure to antidepressants.  

Ruta Nonacs, MD PhD

Rommel AS, Momen NC, Molenaar NM, Liu X, Munk-Olsen T, Bergink V.  Long-term prenatal effects of antidepressant use on the risk of affective disorders in the offspring: a register-based cohort study.  Neuropsychopharmacology. 2021 Jul;46(8):1518-1525. 

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