Prenatal Valproate Exposure Tied to Psychiatric Disorders in Late Childhood

Risk by age 18 years was driven by disorders within the neurodevelopmental spectrum

By Lori Solomon HealthDay Reporter

WEDNESDAY, May 24, 2023 (HealthDay News) — Prenatal exposure to the antiepileptic medication valproate is associated with an increased risk for later psychiatric disorders among children of mothers with epilepsy, according to a study published online April 17 in JAMA Neurology.

Julie Werenberg Dreier, Ph.D., from Aarhus University in Denmark, and colleagues examined the association between prenatal exposure to antiseizure medication (ASM) with a spectrum of psychiatric disorders in childhood and adolescence among children of mothers with epilepsy. The analysis included 38,661 children of mothers with epilepsy born in Denmark, Finland, Iceland, Norway, and Sweden between 1996 and 2017.

The researchers found that 42.6 percent of children were prenatally exposed to ASM. Prenatal valproate exposure was associated with an increased risk for the combined psychiatric end point (adjusted hazard ratio [aHR], 1.80; cumulative risk at 18 years in ASM-exposed children, 42.1 versus 31.3 percent in unexposed children), which was driven mainly by disorders within the neurodevelopmental spectrum. There was no increased risk for psychiatric disorders seen with prenatal exposure to lamotrigine, carbamazepine, or oxcarbazepine, while there were associations for prenatal exposure to topiramate with attention-deficit/hyperactivity disorder (aHR, 2.38) and exposure to levetiracetam with anxiety (aHR, 2.17) and attention-deficit/hyperactivity disorder (aHR, 1.78).

“This study provides reassuring evidence that lamotrigine, carbamazepine, and oxcarbazepine are not associated with long-term behavioral or developmental disorders but cannot rule out risks with higher doses,” the authors write.

Several authors disclosed ties to the pharmaceutical industry.