Valproate in Pregnancy Linked to Lower IQ in Children

Dose-dependent finding supports limiting use of valproate in women of childbearing age

WEDNESDAY, April 15 (HealthDay News) -- The use of valproate in pregnant women with epilepsy is associated with a higher risk of impaired cognitive function in their children at the age of 3, according to research published in the April 16 issue of the New England Journal of Medicine.

Kimford J. Meador, M.D., of Emory University in Atlanta, and colleagues performed an interim analysis of data from 309 children born to mothers with epilepsy who took monotherapy with different agents during pregnancy.

The researchers note that the mean IQ was 101 for children exposed to lamotrigine, 99 for phenytoin, 98 for carbamazepine and 92 for valproate, taking into account maternal IQ and age, drug dose, gestational-age-at-birth and preconception folate use. The effect of valproate was found to be dose dependent. The findings suggest that valproate not be used as a first-choice treatment in women who could become pregnant, the authors write.

"Because of the risks associated with a loss of seizure control during pregnancy, changes from valproate to another antiepileptic drug should be made and evaluated before conception. By the time a woman realizes that she is pregnant, switching drugs is unlikely to reduce the risk of birth defects," writes Torbjorn Tomson, M.D., of the Karolinska Institute in Stockholm, Sweden, in an accompanying editorial. "For women taking high doses of valproate, dose reduction may be reasonable, but only after careful risk-benefit assessment by the physician."

Several of the authors disclosed financial and other relationships with pharmaceutical companies and epilepsy organizations; the editorial author chairs a pregnancy registry supported by pharmaceutical companies.

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