Risks of Prenatal Exposure to Antiseizure Medications

Prenatal exposure to antiseizure medications (ASM), including valproate, topiramate, and several duotheraphies, may be associated with an increased risk of child autism spectrum disorder (ASD), intellectual disability (ID), and other neurodevelopmental disorders.

“Women with epilepsy frequently require ASM during pregnancy, and precise knowledge is needed about the safety for the exposed child,” wrote Marte-Helene Bjørk, MD, PhD, associate professor in the Department of Clinical Medicine, University of Bergen (Bergen, Norway), and colleagues. “Five in 1000 pregnant women use ASMs, and this use is increasing.”

The study aimed to determine if the use of ASMs in monotheraphy and duotheraphy may increase the risk of neurodevelopmental disorders in children who were exposed to the medications prenatally from maternal prescription fills between last menstrual period and birth.

Investigators used data from the Nordic register-based study of antiepileptic drugs in pregnancy (SCAN-AED), which included 4,494,926 mother-child pairs. Additionally, investigators estimated the cumulative incidence of a neurodevelopmental disorder in both exposed and unexposed children who were 8 years of age.

Among 21,634 unexposed children of mothers with epilepsy, 1.5% had a diagnosis of ASD and 0.8% of ID by age 8 years. In comparison, 3.1% of children of the same age of mothers with epilepsy exposed to topiramate (4.3%) and valproate monotherapy (2.7%) were diagnosed with ASD, and 2.4% with ID. After topiramate exposure, the adjusted hazard ratios (aHRs) were 2.8 95% CI, 1.4-5.7) for ASD and 3.5 (95% CI, 1.4-8.6) for ID. The aHRs following valproate exposure were 2.9 (95% CI, 1.7-3.3) and 2.5 (95% CI, 1.7-3.7), respectively. Increased ASM doses were associated with higher aHRs when compared with individuals from the general population.

The duotherapies levetiracetam with carbamazepine and lamotrigine with topiramate were associated with increased risks of neurodevelopmental disorders. There was no increased risk associated with the duotheraphy levetiracetam and lamotrigine.

According to researchers, the study is the largest study of neurodevelopmental outcomes of prenatal ASM exposure to date, and the high-quality data observed provided a large enough sample size to investigate the prenatal exposure to 15 monotherapies and duotherapies.

“In conclusion, prenatal exposure to topiramate and valproate was associated with a risk of ASD and ID, which increased with higher doses,” noted researchers. “ASM duotherapies, except lamotrigine with levetiracetam, were similarly associated with neurodevelopmental disorders.”

— Jessica Ganga

Reference:

Bjørk M, Zoega, H, Leinonen M, et al. Association of prenatal exposure to antiseizure medication with risk of autism and intellectual disability. JAMA Neurology. Published online May 31, 2022. https://jamanetwork.com/journals/jamaneurology/fullarticle/2793003