Attention‐Deficit/Hyperactivity Disorder in Children Following Prenatal Exposure to Antidepressants: results from the Norwegian Mother, Father and Child Cohort Study

Objective To determine the association between child ADHD and prenatal exposure to selective serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitor antidepressants, by timing and duration, with quantification of bias due to exposure misclassification. Design Norwegian Mother, Father and Child Cohort Study and national health registries. Setting Nation-wide, Norway. Population 6395 children born to women who 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 before pregnancy (discontinuers, n=349). Main outcome measure Diagnosis of ADHD or filled prescription for ADHD medication in children, and mother-reported symptoms of ADHD by child age 5 years. Results When the hazard was averaged over the duration of the study 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. In early childhood, the risk for ADHD was lower with prenatal SSRI/SNRI exposure compared with no exposure, 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 maternal depression/anxiety. The elevated risk at child age 7-9 years needs to be elucidated.