While previous studies have reported an association between antidepressant use during pregnancy and increased risk of attention-deficit/hyperactivity disorder (ADHD) in the exposed offspring, one important limitation of these studies is that they often did not adequately control for potential confounding factors. For example, risk in antidepressant-exposed children has often been compared to risk in healthy unexposed children, an approach that would not account for genetic or environmental factors specific to mothers using antidepressants during pregnancy (confounding by indications.

To better control for unmeasured risk factors, researchers from the University of Groningen set up a case-control sibling study analyzing data from their prescription database. Children receiving medication for ADHD (cases) before the age of 16 years were matched to their siblings who were not receiving such medication (controls). Prenatal exposure was defined as at least two prescriptions for the mother of any antidepressant during pregnancy.  

In total, the analysis included 2,833 children (1,304 cases and 1,529 controls). Prenatal exposure to antidepressants did not differ between cases and sibling controls: 2.2% and 2.4%, respectively. After adjusting for maternal age, use of psychostimulants, opioids, and antiepileptic drugs by the mother, they calculated an adjusted odds ratio (OR) of 1.11 (95% CI 0.67-1.83) for the risk of ADHD in the offspring with prenatal exposure to antidepressants.  

Consistent with other studies, including a large meta-analysis, this study indicates no increased risk of ADHD in offspring following in utero exposure to antidepressants. 

Ruta Nonacs, MD PhD

Hartwig CAM, Robiyanto R, de Vos S, Bos JHJ, van Puijenbroek EP, Hak E, Schuiling-Veninga CCM. In utero antidepressant exposure not associated with ADHD in the offspring: A case control sibling design. Front Pharmacol. 2022 Nov 10; 13:1000018.

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