• Sonia Hernández-Díaz, Loreen Straub, Brian T Bateman, Yanmin Zhu, Helen Mogun, Katherine L Wisner, Kathryn J Gray, Barry Lester, Christopher J McDougle, Elyse DiCesare, Page B Pennell, and Krista F Huybrechts.
• From the Department of Epidemiology, Harvard T.H. Chan School of Public Health (S.H.-D.), the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School (L.S., Y.Z., H.M., E.D., K.F.H.), the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women's Hospital (K.J.G.), and the Department of Psychiatry, Harvard Medical School (C.J.M.), Boston, and the Lurie Center for Autism, Massachusetts General Hospital, Lexington (C.J.M.) - all in Massachusetts; the Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA (B.T.B.); the Asher Center for the Study and Treatment of Depressive Disorders, Department of Psychiatry and Behavioral Sciences, and the Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago (K.L.W.); the Center for the Study of Children at Risk, Departments of Psychiatry and Pediatrics, Alpert Medical School of Brown University, and Women and Infants Hospital, Providence, RI (B.L.); and the Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh (P.B.P.).
• N. Engl. J. Med. 2024 Mar 21; 390 (12): 106910791069-1079.

BackgroundMaternal use of valproate during pregnancy has been associated with an increased risk of neurodevelopmental disorders in children. Although most studies of other antiseizure medications have not shown increased risks of these disorders, there are limited and conflicting data regarding the risk of autism spectrum disorder associated with maternal topiramate use.MethodsWe identified a population-based cohort of pregnant women and their children within two health care utilization databases in the United States, with data from 2000 through 2020. Exposure to specific antiseizure medications was defined on the basis of prescription fills from gestational week 19 until delivery. Children who had been exposed to topiramate during the second half of pregnancy were compared with those unexposed to any antiseizure medication during pregnancy with respect to the risk of autism spectrum disorder. Valproate was used as a positive control, and lamotrigine was used as a negative control.ResultsThe estimated cumulative incidence of autism spectrum disorder at 8 years of age was 1.9% for the full population of children who had not been exposed to antiseizure medication (4,199,796 children). With restriction to children born to mothers with epilepsy, the incidence was 4.2% with no exposure to antiseizure medication (8815 children), 6.2% with exposure to topiramate (1030 children), 10.5% with exposure to valproate (800 children), and 4.1% with exposure to lamotrigine (4205 children). Propensity score-adjusted hazard ratios in a comparison with no exposure to antiseizure medication were 0.96 (95% confidence interval [CI], 0.56 to 1.65) for exposure to topiramate, 2.67 (95% CI, 1.69 to 4.20) for exposure to valproate, and 1.00 (95% CI, 0.69 to 1.46) for exposure to lamotrigine.ConclusionsThe incidence of autism spectrum disorder was higher among children prenatally exposed to the studied antiseizure medications than in the general population. However, after adjustment for indication and other confounders, the association was substantially attenuated for topiramate and lamotrigine, whereas an increased risk remained for valproate. (Funded by the National Institute of Mental Health.).Copyright © 2024 Massachusetts Medical Society.

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