Attention-deficit/hyperactivity disorder in children following prenatal exposure to antidepressants: results from the Norwegian mother, father and child cohort study.

Lupattelli, A; Mahic, M; Handal, M; Ystrom, E; Reichborn-Kjennerud, T; Nordeng, H · BJOG · 2021

prospective_cohort · Level II

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Abstract

To determine the association between child attention-deficit/hyperactivity disorder (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. Norwegian Mother, Father and Child Cohort Study and national health registries. Nationwide, Norway. A total of 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 6 months before pregnancy (discontinuers, n = 349). Diagnosis of ADHD or filled prescription for ADHD medication in children, and mother-reported symptoms of ADHD by child age 5 years. 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% CI 0.76-1.51 versus non-medicated; wHR 1.53, 95% CI 0.77-3.07 versus 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 to -0.08); this risk became elevated at child age 7-9 years (wHR 1.93, 95% CI 1.22-3.05). Maternal depression/anxiety before pregnancy was independently associated with child ADHD. 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. Women with depression who use antidepressants in pregnancy do not have greater risk of having children with ADHD. Findings in school-age children needs follow up.

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