NEW YORK (Reuters Health) – Use of valproate during pregnancy compared with other antiepileptic drugs is associated with reduced cognitive function in offspring at 3 years of age, according to findings from a prospective study conducted in the US and the UK.

“Valproate should not be used as a first-line antiepileptic drug in pregnant women or — since data indicate half of pregnancies are unplanned — in women of childbearing potential,” Dr. Kimford J. Meador, at Emory University in Atlanta, and co-authors advise in the New England Journal of Medicine for April 16.

The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study group conducted an interim analysis of 258 children at 2 and/or 3 years of age, whose mothers were pregnant between 1999 and 2004 while taking lamotrigine (n = 84), phenytoin (n = 48), carbamazepine (n = 73), or valproate (n = 53) as monotherapy for epilepsy.

The mean IQ of children exposed to valproate was 92, significantly lower than the mean scores of 101 for lamotrigine exposure (p = 0.009), 99 for phenytoin (p = 0.04), and 98 for carbamazepine (p = 0.04).

Dr. Meador’s group cautions, however, that women should not abruptly stop taking valproate if they become pregnant.

In discussing the clinical implications in an editorial, Dr. Torbjorn Tomson states, “Most major congenital malformations can be detected with the use of prenatal screening, and many can be successfully treated surgically after birth, but cognitive impairment cannot.”

“Women with epilepsy should be taught the importance of planning their pregnancies,” says Dr. Tomson, from the Karolinska Institute in Stockholm, and “discussion of the current findings should be included in prepregnancy counseling.”

Waiting until a woman is pregnant before switching antiepileptic drugs is likely to be too late to protect the fetus, the editorialist notes, because safely switching antiepileptic drugs typically requires a period of months, with use of polytherapy during the interim.

A reduced dose of valproate to below 800 mg/d may be an option, but only after careful assessment by the physician, given that the risks of uncontrolled seizures must be balanced against the risks of valproate use.

Reference:
N Engl J Med 2009;360:1597-1605,1667-1669.