Fetal Exposure to Valproate Linked to Lower IQ at Age 6

Exposure to high doses of valproate, not other antiepileptics, linked to reduced cognitive abilities

WEDNESDAY, Jan. 23 (HealthDay News) -- Fetal exposure to valproate is associated with lower IQ compared with exposure to other antiepileptic drugs, according to a study published online Jan. 23 in The Lancet Neurology.

Kimford J. Meador, M.D., from Emory University in Atlanta, and colleagues conducted a prospective observational multicenter study to examine the effects of commonly used antiepileptic drugs on cognitive outcomes in children up to 6 years of age. A total of 305 mothers with epilepsy who were treated with antiepileptic drug monotherapy (carbamazepine, lamotrigine, phenytoin, or valproate), and their 311 children, were included in the primary analysis.

Six-year follow-up was completed by 224 children. The researchers found that exposure to valproate correlated with significantly lower IQ at age 6, compared with exposure to carbamazepine, lamotrigine, or phenytoin. Exposure to high doses of valproate, but not other drugs, correlated negatively with IQ, verbal ability, nonverbal ability, memory, and executive function. Children exposed to valproate versus other drugs did poorly on measures of verbal and memory abilities, and did poorly on measures of nonverbal and executive functions compared with lamotrigine. For infants exposed to any antiepileptic drug, IQ improved with age; IQ at age 6 was associated with IQ at younger ages.

"In conclusion, we noted that fetal valproate exposure has dose-dependent associations with reduced cognitive abilities across a range of domains at 6 years of age," the authors write. "Women requiring an antiepileptic drug and their clinicians should be aware of these findings in choosing their treatment."

Several authors disclosed financial ties to the pharmaceutical industry; one author served as an expert witness in litigation related to the diagnosis of fetal anticonvulsant syndrome.

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