Valproate use in pregnancy linked with birth defects: more than 1,100 mg/day boosts the risk: preliminary analysis.

BOSTON -- Women who take sodium valproate during pregnancy are at greater risk of having a child with a fetal malformation than are those taking other antiepileptic drugs, according to a preliminary analysis of the 40-month data from an ongoing Australian registry of epilepsy treatment and pregnancy.

Moreover, women who take more than 1,100 mg/day of valproate face a significantly greater risk of fetal malformation than those taking smaller doses of the drug, Dr. Frank J. Vajda reported at the annual meeting of the American Epilepsy Society.

Of 403 pregnancies in women taking antiepileptic drugs (AEDs), 87.8% resulted in a healthy live birth and 5.2% resulted in a live birth of a child with fetal malformations, ranging from neurologic to genitourinary to skeletal abnormalities. The remaining pregnancies ended in spontaneous abortion or premature death in utero.

The fetal malformation rate was significantly greater in pregnancies exposed to valproate in the first trimester, compared with those exposed to all other AEDs in the first trimester. (16.1% vs. 2.4%). Additionally, the incidence of fetal malformations was significantly higher in women taking valproate than in those taking no AEDs (16.1% vs. 3.1%).

Among women taking more than 1,100 mg/day of the drug, fetal malformations occurred in 16 out of 53 births, compared with 2 of 66 births in women taking less than 1,100 mg/day (30% vs. 3%), said Dr. Vajda of the Australian Center for Clinical Neuropharmacology at St. Vincent's Hospital, Fitzroy, Australia.

Previously, Dr. Vajda and colleagues analyzed 30-month data from the registry to show that women taking valproate in ...