Aarhus, Denmark—Counseling is necessary when expectant mothers are prescribed valproate but possibly not other antiepileptic drugs, according to a new study.

A report published in JAMA Network Open sought to determine if prenatal exposure to valproate and other antiepileptic drugs was associated with increased risk of attention-deficit/hyperactivity disorder (ADHD) in children.

To help find out, Danish researchers from Aarhus University Hospital focused on more than 913,000 children in Denmark in the observational study. Exposure to antiepileptic drugs was defined as expectant mothers redeeming one or more prescriptions for the medications during pregnancy.

The study identified 580 children as having been exposed to valproate during pregnancy and, of them, 8.4% received an ADHD diagnosis versus 3.2% among those not exposed. The study was limited because of the use of registry data, which offered no information on whether the women actually used the medication or how much was actually taken, according to the researchers.

The study team adds that the absolute 15-year risk of ADHD in children exposed to valproate in pregnancy was higher than those not exposed to the drug, although no associations were established between other antiepileptic drugs in the study and ADHD.

“Maternal use of valproate, but not other AEDs, during pregnancy was associated with an increased risk of ADHD in the offspring,” the authors conclude. “These findings have important implications for the counseling of women of childbearing potential using valproate.”

Background information in the report points out that this research adds to the increasing number of studies suggesting that valproate in pregnancy is associated with a number of adverse neurodevelopmental outcomes, including poor cognitive function and autism, in addition to an increased risk of congenital malformations.

Calling the association between prenatal exposure to valproate and an increased risk of ADHD “quite robust,” researchers emphasize that the risk of ADHD was also increased in valproate-exposed offspring compared with the offspring of women who used valproate prior to but not during their pregnancy and compared with children who were prenatally exposed to lamotrigine.

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