Prenatal Exposure to Antiseizure Medications and Risk of Epilepsy in Children of Mothers With Epilepsy

• Published in: JAMA Network Open
• Main Authors: Dreier, Julie Werenberg, Christensen, Jakob, Igland, Jannicke, Gissler, Mika, Leinonen, Maarit K., Vegrim, Håkon Magne, Sun, Yuelian, Tomson, Torbjörn, Zoega, Helga, Bjørk, Marte-Helene, Bromley, Rebecca L.
• Format: Article in Journal/Newspaper
• Language: English
• Published: American Medical Association (AMA) 2024
• Subjects: General Medicine; Norway; Iceland
• Online Access: http://dx.doi.org/10.1001/jamanetworkopen.2023.56425; https://jamanetwork.com/journals/jamanetworkopen/articlepdf/2815466/dreier_2024_oi_231659_1708128504.13327.pdf

Importance Use of valproate and certain other antiseizure medications (ASMs) in pregnancy is associated with abnormal fetal brain development with potential long-term implications for the child. Objective To examine whether use of valproate and other ASMs in pregnancy among mothers with epilepsy is associated with epilepsy risk in their children. Design, Setting, and Participants This prospective, population-based register cohort study included singletons born to mothers with epilepsy in Denmark, Finland, Iceland, Norway, and Sweden from January 1, 1996, to December 31, 2017. Data analysis was performed from October 2022 to December 2023. Exposure Redeemed prescription for an ASM from 30 days before pregnancy until birth. Main Outcomes and Measures The main outcome was epilepsy in children, assessed using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses from hospital care. Adjusted hazard ratios (AHRs) and 95% CIs were estimated using Cox proportional hazards regression. Secondary analyses included dose-response analyses, analyses using children of mothers who discontinued ASM prior to pregnancy as the reference, and sibling analyses. Results This cohort study included 38 663 children of mothers with epilepsy (19 854 [51.4%] boys). Children were followed up from birth; the mean length of follow-up was 7.2 years (range 0-22 years). Compared with 22 207 children of mothers not using an ASM in pregnancy, increased risks of epilepsy in children of mothers who used valproate in pregnancy (monotherapy: AHR, 2.18; 95% CI, 1.70-2.79; polytherapy: AHR, 2.10; 95% CI, 1.49-2.96) were observed. However, there was no dose-dependent association, and there was a similar risk of epilepsy in siblings who were exposed and unexposed to valproate (AHR, 0.95; 95% CI, 0.50-1.82). Prenatal exposure to topiramate monotherapy was associated with increased risk of epilepsy (AHR, 2.32; 95% CI, 1.30-4.16), and the risk was greater for higher doses, but the risk attenuated in ...