Association of prenatal antidepressant use with internalizing behaviors from kindergarten to adolescence.

BACKGROUND To examine, using repeated measures, whether prenatal serotonin/norepinephrine reuptake inhibitor (SRI) antidepressant exposure is associated with increased anxious behaviors at kindergarten age and anxiety and/or depression behaviors after kindergarten and into adolescence. METHODS This population-based retrospective cohort study included all live singleton infants delivered in British Columbia, Canada between January 2001 and December 2012 with complete outcome data. Follow-up lasted until December 2022. Logistic regression models were used to estimate unadjusted and adjusted odds ratios (OR). To minimize confounding, high-dimensional propensity score adjustment and a matched discordant sibling-pair analysis were conducted. RESULTS Prenatal SRI exposure was associated with increased anxious behaviors in kindergarten (OR 1.77 [95% CI 1.59-1.97]) and anxiety and/or depression diagnostic codes in later childhood or adolescence (OR 2.09 [95% CI 1.97-2.22]). These associations attenuated but remained positive after high-dimensional propensity score adjustment; however, the associations did not remain in the conditional logistic regression of discordant sibling pairs (aORs 0.92 [95% CI 0.61-1.37] and 1.02 [95% CI 0.79-1.33]). Regardless of SRI exposure, children with high levels of anxious behaviors at kindergarten were more likely to receive anxiety and/or depression diagnostic codes later on (SRI exposed: aOR 1.59 [95% CI 1.24-2.06]; SRI unexposed: aOR 1.64 [95% CI 1.51-1.77]). CONCLUSIONS The associations of prenatal SRI exposure with increased internalizing behaviors at kindergarten and into adolescence are likely due to shared genetics or environmental factors. Findings also suggested kindergarten as a time for targeted interventions to address developmental vulnerabilities and prevent later development of anxiety and/or depression.