BANGKOK, THAILAND — Expressive and receptive language abilities are lower in 3-year-olds who were exposed to sodium valproate in utero than in children exposed to other individual antiepileptic drugs during gestation, according to a subanalysis of the Neurodevelopmental Effects of Antiepileptic Drugs study.
Valproate exposure was associated with a 10-point difference on both language measures compared with exposure to phenytoin, carbamazepine, or lamotrigine—a difference that is statistically significant and clinically important, Gus A. Baker, Ph.D., said at the World Congress of Neurology.
The prospective, observational Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study included 303 pregnant women taking sodium valproate, carbamazepine, lamotrigine, or phenytoin as monotherapy. Enrollment occurred during 1999-2004 in 25 epilepsy centers in the United States and the United Kingdom. The primary outcome is cognitive performance of the children at 6 years of age.
Dr. Baker, a primary investigator in the U.K. study and coinvestigator in the overall study, presented the results of the drugs' effect on expressive and receptive language development among 234 children who were 3 years old at the time of assessment. Test scores were adjusted for factors known to affect child intellect, including maternal IQ, maternal age, gestational age, antiepileptic drug (AED) dose, and prenatal exposure to folate.
“Maternal IQ, AED dose, maternal age, gestational age, and preconceptional exposure to folate were significant factors predicting the scores, as we would expect,” said Dr. Baker, director of the division of neurosciences at the Walton Centre for Neurology and Neurosurgery, Liverpool, England, and professor of clinical neuropsychology at the University of Liverpool. “But we also showed that overall, the scores for valproate-exposed children were significantly lower than all other drugs and the magnitude of the effect was greater for verbal than nonverbal language.”
Testing showed that the children exposed to valproate scored significantly lower on measures of expressive language (mean score of 91 vs. 102 for carbamazepine, 104 for lamotrigine, and 101 for phenytoin) and receptive language (mean score of 89 vs. 97 for carbamazepine, 101 for lamotrigine, and 101 for phenytoin). On visual motor construction and nonverbal intellectual ability, children exposed to valproate scored lower, but not significantly lower, than children exposed to the other drugs.
The study confirms earlier NEAD findings, which strongly suggest that women of childbearing age who need AED therapy should avoid valproate if possible. “For women for whom sodium valproate is the first choice because of the nature of their seizures, we should be thinking about reducing the dose to the least possible effective level,” Dr. Baker said. “In an ideal world, we would have preconception counseling and would be thinking of an alternative drug several years before pregnancy occurs.”