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Attention-Deficit/Hyperactivity Disorder in Children Following Prenatal Exposure to Antidepressants: results from the Norwegian Mother, Father and Child Cohort Study
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  • Angela Lupattelli,
  • Milada Mahic,
  • Marte Handal,
  • Eivind Ystrom,
  • Ted Reichborn-Kjennerud,
  • Hedvig Nordeng
Angela Lupattelli
University of Oslo Faculty of Mathematics and Natural Sciences
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Milada Mahic
Norwegian Institute of Public Health
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Marte Handal
Norwegian Institute of Public Health
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Eivind Ystrom
Norwegian Institute of Public Health
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Ted Reichborn-Kjennerud
Norwegian Institute of Public Health
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Hedvig Nordeng
University of Oslo Faculty of Mathematics and Natural Sciences
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Abstract

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.

Peer review status:Published

23 Sep 2020Submitted to BJOG: An International Journal of Obstetrics and Gynaecology
25 Sep 2020Submission Checks Completed
25 Sep 2020Assigned to Editor
27 Sep 2020Reviewer(s) Assigned
01 Nov 2020Review(s) Completed, Editorial Evaluation Pending
07 Dec 2020Editorial Decision: Revise Major
18 Jan 20211st Revision Received
19 Jan 2021Submission Checks Completed
19 Jan 2021Assigned to Editor
19 Feb 2021Reviewer(s) Assigned
10 Mar 2021Review(s) Completed, Editorial Evaluation Pending
31 Mar 2021Editorial Decision: Accept
13 May 2021Published in BJOG: An International Journal of Obstetrics & Gynaecology. 10.1111/1471-0528.16743