Sarah Hjorth1, Angela Lupattelli1, Marte Handal2, Olav Spigset3,4, Eivind Ystrom1,2,5, Hedvig Nordeng1,6. 1. PharmacoEpidemiology and Drug Safety Research Group, Department of Pharmacy, and PharmaTox Strategic Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway. 2. Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway. 3. Department of Clinical Pharmacology, St. Olav's University Hospital, Trondheim, Norway. 4. Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. 5. PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway. 6. Department of Child Health and Development, Norwegian Institute of Public Health, Oslo, Norway.
Abstract
PURPOSE: To estimate the association between Attention-Deficit/Hyperactivity Disorder (ADHD) in children in preschool and primary school, and prenatal exposure to non-steroidal anti-inflammatory drugs (NSAIDs) by timing and duration. METHODS: This study was based on the Norwegian Mother, Father and Child Cohort Study linked to the Medical Birth Registry of Norway, the Norwegian Patient Registry (NPR) and the Norwegian Prescription Database (NorPD). NSAID exposure was identified by maternal self-report in pregnancy. Child diagnosis of ADHD was obtained from NPR and NorPD. Symptoms of ADHD at age 5 years were measured using Conners' Parent Rating Scale-Revised, where higher scores correspond to more symptoms. To account for time-varying exposure and confounders, marginal structural models were fitted to estimate hazard ratios and mean difference in z-scores. RESULTS: The analyses on ADHD diagnosis and ADHD symptoms included 56 340 and 34 961 children respectively. Children exposed to NSAIDs prenatally had no increased risk of ADHD diagnosis (first trimester: HR 1.12, 95% CI 0.86;1.45, second trimester: HR 0.98, 95% CI 0.69;1.38, third trimester: HR 0.68, 95% CI 0.31; 1.46) or ADHD symptoms (first trimester: standardized mean difference 0.03, 95% CI -0.03;0.09, second trimester: standardized mean difference 0.03, 95% CI -0.04;0.11, third trimester: standardized mean difference 0.11, 95% CI -0.03; 0.25). There was no duration-response relationship for either outcome. CONCLUSION: Though non-differential misclassification of the exposure may have attenuated results, these findings are reassuring and suggest no substantially increased risk of ADHD diagnosis or symptoms in children prenatally exposed to NSAIDs, regardless of timing or duration.
PURPOSE: To estimate the association between Attention-Deficit/Hyperactivity Disorder (ADHD) in children in preschool and primary school, and prenatal exposure to non-steroidal anti-inflammatory drugs (NSAIDs) by timing and duration. METHODS: This study was based on the Norwegian Mother, Father and Child Cohort Study linked to the Medical Birth Registry of Norway, the Norwegian Patient Registry (NPR) and the Norwegian Prescription Database (NorPD). NSAID exposure was identified by maternal self-report in pregnancy. Child diagnosis of ADHD was obtained from NPR and NorPD. Symptoms of ADHD at age 5 years were measured using Conners' Parent Rating Scale-Revised, where higher scores correspond to more symptoms. To account for time-varying exposure and confounders, marginal structural models were fitted to estimate hazard ratios and mean difference in z-scores. RESULTS: The analyses on ADHD diagnosis and ADHD symptoms included 56 340 and 34 961 children respectively. Children exposed to NSAIDs prenatally had no increased risk of ADHD diagnosis (first trimester: HR 1.12, 95% CI 0.86;1.45, second trimester: HR 0.98, 95% CI 0.69;1.38, third trimester: HR 0.68, 95% CI 0.31; 1.46) or ADHD symptoms (first trimester: standardized mean difference 0.03, 95% CI -0.03;0.09, second trimester: standardized mean difference 0.03, 95% CI -0.04;0.11, third trimester: standardized mean difference 0.11, 95% CI -0.03; 0.25). There was no duration-response relationship for either outcome. CONCLUSION: Though non-differential misclassification of the exposure may have attenuated results, these findings are reassuring and suggest no substantially increased risk of ADHD diagnosis or symptoms in children prenatally exposed to NSAIDs, regardless of timing or duration.
Keywords:
Medical Birth Registry of Norway; Norwegian mother; anti-inflammatory agents; attention deficit disorder with hyperactivity; father and child cohort study; non-steroidal; prenatal exposure delayed effects
Authors: Jennifer M Lye; Julia A Knight; Jasleen Arneja; Ryan A Seeto; Jody Wong; Nadya Adel Khani; Jennifer D Brooks; Robert D Levitan; Stephen G Matthews; Stephen J Lye; Rayjean J Hung Journal: Pediatr Res Date: 2022-07-07 Impact factor: 3.953