Risk of neurodevelopmental disorders after prenatal exposure to antiseizure meds

A new study has examined whether children exposed prenatally to monotherapy or dual therapy with antiseizure medications have an increased risk of neurodevelopmental disorders. Women with epilepsy often require antiseizure medication during pregnancy to prevent seizures. Discontinuation of these medications before or during pregnancy has been associated with uncontrolled seizures and increased maternal mortality. However, the risk of neurodevelopmental disorders in children after prenatal exposure to antiseizure medications is uncertain. The study used data from the Nordic register-based study of antiepileptic drugs in pregnancy (SCAN-AED), which is a population-based cohort study using data from Denmark, Finland, Iceland, Norway and Sweden. The study included almost 4.5 million mother-child pairs with live-born children and available maternal prescription data. Prenatal exposure to antiseizure medications was determined from maternal prescription fills between their last menstrual period and the child’s birth. Read: How to help patients with cognitive symptoms of long COVID The investigators estimated cumulative incidence for autism spectrum disorder (ASD), intellectual disability (ID), or any neurodevelopmental disorder (ASD and/or ID) in exposed and unexposed children at eight years of age. Results showed the following: Among 21,634 unexposed children of mothers with epilepsy, 1.5% had a diagnosis of ASD and 0.8% had ID by age eight years. Monotherapies In children of mothers with epilepsy, 4.3% exposed to topiramate and 2.7% exposed to valproate (both as monotherapies) had ASD, while 3.1% and 2.4%, respectively had ID. After adjustment for potential confounders, the adjusted hazard ratio (aHR) after topiramate exposure was 2.8 (95%CI, 1.4–5.7) for ASD and 3.5 (95%CI, 1.4–8.6) for ID. The aHR after valproate exposure was 2.4 (95%CI, 1.7–3.3) for ASD and 2.5 (95%CI, 1.7–3.7) for ID. Higher topiramate or valproate doses were associated with greater risk. The aHR was 1.7 (95% CI, 1.0–2.8) for any neurodevelopmental disorder associated with topiramate doses < 100 mg/day and 2.9 (95%CI, 1.3–6.7) for doses ≥ 100 mg/day compared with children from the general population. For valproate, the aHR was 2.3 (95%CI, 1.9–2.8) with doses < 750 mg/day and 5.6 (95% CI, 4.7–6.8) with doses ≥ 750 mg/day. No consistent increased risks were observed for neurodevelopmental disorders after prenatal exposure to monotherapy with lamotrigine, levetiracetam, carbamazepine, oxcarbazepine, gabapentin, pregabalin, clonazepam or phenobarbital. Dual therapies The risk associated with exposure to dual therapy was only assessed for the combined outcome of any neurodevelopmental disorder because of too few cases when considering only ASD or ID. Levetiracetam–carbamazepine and lamotrigine–topiramate were associated with increased risks of neurodevelopmental disorders in children of women with epilepsy. The eight-year cumulative incidence of neurodevelopmental disorders for levetiracetam–carbamazepine was 5.7% (aHR, 3.5; 95%CI, 1.5–8.2), and 7.5% for lamotrigine–topiramate (aHR, 2.4; 95%CI, 1.1–4.9). Lamotrigine–valproate (aHR 1.7) and lamotrigine–oxcarbazepine (aHR 2.1) dual therapies were also associated with increased risk. No increased risk of neurodevelopmental disorders was found with levetiracetam–lamotrigine dual therapy (8-year cumulative incidence, 1.6%; aHR, 0.9; 95%CI, 0.3–2.5). The authors concluded that in this cohort study, prenatal exposure to topiramate or valproate monotherapy was associated with an increased risk of neurodevelopmental disorders and the risk increased with higher doses. In addition, several antiseizure medication dual therapies were associated with increased risks of neurodevelopmental disorders. Read: Blood test for detecting early Alzheimer’s disease shows promise Reference 1. Bjørk MH, Zoega H, Leinonen MK, et al. Association of prenatal exposure to antiseizure medication with risk of autism and intellectual disability. JAMA Neurol 2022; Published online May 31, 2022. https://jamanetwork.com/journals/jamaneurology/fullarticle/2793003#:~:text=Findings%20In%20this%20cohort%20study,spectrum%20disorders%20and%20intellectual%20disability (accessed May 31, 2022)

Risk of neurodevelopmental disorders after prenatal exposure to antiseizure meds

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