Association of Prenatal Exposure to Antiseizure Medication With Risk of Autism and Intellectual Disability

• Published in: JAMA Neurology
• Main Authors: Bjørk, Marte-Helene, Zoega, Helga, Leinonen, Maarit K, Cohen, Jacqueline M, Dreier, Julie Werenberg, Furu, Kari, Gilhus, Nils Erik, Gissler, Mika, Hálfdánarson, Óskar, Igland, Jannicke, Sun, Yuelian, Tomson, Torbjörn, Alvestad, Silje, Christensen, Jakob
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2022
• Subjects: ANTIEPILEPTIC DRUGS; EPILEPSY; IN-UTERO EXPOSURE; MORTALITY; ORAL CLEFTS; OUTCOMES; PREGNANCY; TOPIRAMATE; WOMEN; Norway; Iceland
• Online Access: https://pure.au.dk/portal/da/publications/association-of-prenatal-exposure-to-antiseizure-medication-with-risk-of-autism-and-intellectual-disability(885d1e09-a1cd-4e59-8382-81badb37b134).html; https://doi.org/10.1001/jamaneurol.2022.1269; https://pure.au.dk/ws/files/353520469/jamaneurology_bjrk_2022_oi_220027_1656444956.23113.pdf; http://www.scopus.com/inward/record.url?scp=85134248684&partnerID=8YFLogxK

Importance: Women with epilepsy frequently need antiseizure medication (ASM) to prevent seizures in pregnancy. Risk of neurodevelopmental disorders after prenatal exposure to AMSs is uncertain. Objective: To determine whether children exposed prenatally to ASMs in monotherapy and duotherapy have increased risk of neurodevelopmental disorders. Design, Setting, and Participants: The Nordic register-based study of antiepileptic drugs in pregnancy (SCAN-AED) is a population-based cohort study using health register and social register data from Denmark, Finland, Iceland, Norway, and Sweden (1996-2017; analysis performed February 2022). From 4 702 774 alive-born children with available mother-child identities and maternal prescription data, this study included 4 494 926 participants. Children from a multiple pregnancy or with chromosomal disorders or uncertain pregnancy length were excluded (n = 207 848). Exposures: Prenatal exposure to ASM determined from maternal prescription fills between last menstrual period and birth. Main Outcomes and Measures: We estimated cumulative incidence at age 8 years in exposed and unexposed children. Cox regression adjusted for potential confounders yielded adjusted hazard ratios (aHRs) with 95% CIs for autism spectrum disorder (ASD), intellectual disability (ID), or any neurodevelopmental disorder (ASD and/or ID). Results: A total of 4 494 926 children were included; 2 306 993 (51.3%) were male, and the median (IQR) age at end of follow-up was 8 (4.0-12.1) years. Among 21 634 unexposed children of mothers with epilepsy, 1.5% had a diagnosis of ASD and 0.8% (numerators were not available because of personal data regulations in Denmark) of ID by age 8 years. In same-aged children of mothers with epilepsy exposed to topiramate and valproate monotherapy, 4.3% and 2.7%, respectively, had ASD, and 3.1% and 2.4% had ID. The aHRs for ASD and ID after topiramate exposure were 2.8 (95% CI, 1.4-5.7) and 3.5 (95% CI, 1.4-8.6), respectively, and after valproate exposure were 2.4 (95% CI, 1.7-3.3) ...