Angela Lupattelli

and 5 more

Objective: To quantify the association between prenatal exposure to selective serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitor antidepressants and ADHD in offspring, with quantification of exposure misclassification bias. Design: Norwegian Mother, Father and Child Cohort Study (MoBa), linked to national health registries. Setting: Norway. Population: 6395 children born to women who self-reported depression/anxiety in pregnancy and were either medicated with SSRI/SNRI in pregnancy (n=818) or non-medicated (n=5228), or did not report depression/anxiety but used antidepressants six months prior to pregnancy (discontinuers, n=349). Main outcome measure: Diagnosis of ADHD or redeemed prescription for ADHD medication in children, and mother-reported symptoms of ADHD at child age five years. Results: When the hazard was averaged over the duration of the study’s follow-up, there was no difference in ADHD risk between ever in-utero SSRI/SNRI-exposed children and comparators (weighted Hazard Ratio (wHR): 1.07, 95% Confidence Interval (CI): 0.76-1.51, vs. non-medicated; wHR: 1.53, 95% CI: 0.77-3.07, vs. discontinuers). Underestimation of effects due to exposure misclassification was modest. At early childhood, the risk for ADHD was lower with prenatal SSRI/SNRI exposure compared with non-medicated, and so were ADHD symptoms (weighted β: -0.23, 95% CI: -0.39, -0.08); this risk became elevated at child age 7-9 years (wHR: 1.93, 95% CI: 1.22-3.05). Maternal depression/anxiety prior to pregnancy was independently associated with child ADHD. Conclusion: Prenatal SSRI/SNRI exposure is unlikely to considerably increase the risk of child ADHD beyond that posed by the underlying psychiatric illness. The elevated risk at child age 7-9 years needs to be further elucidated.