Prenatal exposure to antiseizure therapy linked to risk for neurodevelopmental disorders

Prenatal exposure to topiramate, valproate and select duotherapies was associated with increased risk for autism spectrum disorder and intellectual disability, according to a study published in JAMA Neurology.

“Women with epilepsy frequently require antiseizure medication during pregnancy, and precise knowledge is needed about the safety for the exposed child,” Marte-Helene Bjork, MD, PhD, associate professor of neurology at the University of Bergen in Norway, and colleagues wrote.

Researchers sought to determine whether children who were prenatally exposed to monotherapeutic or duotherapeutic antiseizure medication (ASM) were at greater risk for developing neurodevelopmental disorders.

The population-based cohort study utilized health and social register data from Denmark, Finland, Iceland, Norway and Sweden from 1996 to 2017 to identify nearly 4.5 million alive-born children (51.3% boys) with available mother-child identities and maternal prescription information.

The authors determined prenatal ASM exposure from prescriptions filled by mothers between their last menstrual period and birth and estimated cumulative incidence at 8 years in exposed and unexposed children.

Results showed no consistently increased risks for neurodevelopmental disorders following exposure to monotherapy with lamotrigine, levetiracetam, carbamazepine, oxcarbazepine, gabapentin, pregabalin, clonazepam or phenobarbital.

Conversely, duotherapies of levetiracetam with carbamazepine (8-year cumulative incidence, 5.7%; adjusted HR = 3.5; 95% CI, 1.5-8.2) and lamotrigine with topiramate (8-year cumulative incidence, 7.5%; aHR = 2.4; 95% CI, 1.1-4.9) were associated with increased risks for neurodevelopmental disorders in children of women with epilepsy. However, no increased risk was associated with levetiracetam with lamotrigine.

Further, among 21,634 unexposed children of mothers with epilepsy, 1.5% were diagnosed with autism spectrum disorder and 0.8% with intellectual disability (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) and 2.5 (95% CI, 1.7-3.7).

“The risks identified by this study are likely an underrepresentation of the risks associated with these exposures,” Bjork and colleagues wrote.