There have long been concerns regarding the use of the anticonvulsant valproate (Depakote) during pregnancy.  First trimester use of valproate has been associated with a 3-5% risk of neural tube defects, as well as an increased risk of other malformations affecting the heart, limbs, and genitals. A recent report published in the New England Journal of Medicine indicates that in utero exposure to valproate may also result in lower IQ.

In this study, researchers from the United States and the United Kingdom presented data from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study, a prospective, observational, multicenter study which followed women  with epilepsy who were taking a single antiepileptic agent (carbamazepine, lamotrigine, phenytoin, or valproate).

A total of 309 children were evaluated at 3 years of age.  The authors reported that children who had been exposed to valproate in utero had significantly lower IQ scores than those who had been exposed to other antiepileptic drugs.  After adjusting for a variety of variables, including maternal IQ, maternal age, drug dosage, gestational age at birth, and maternal preconception use of folate, it was observed that on average children exposed to valproate had IQ scores 6 to 9 points lower than the scores of those exposed to the other anti-epileptic agents.  It was also shown that the association between valproate and lower IQ was dose-dependent, with the worse cognitive outcomes observed in children exposed to doses of valproate higher than 1000mg/day.

These results are consistent with those of previous retrospective studies which have demonstrated poorer cognitive functioning and lower verbal IQ scores in children exposed to valproate in utero as compared to children who were either unexposed or exposed to other antiepileptic-drug monotherapies.  The authors conclude that given these risks, other anticonvulsant agents are preferable in women who are planning a pregnancy.

Ruta Nonacs, MD PhD.

Meador KJ, Baker GA, Browning N, Clayton-Smith J, Combs-Cantrell DT, Cohen M, Kalayjian LA, Kanner A, Liporace JD, Pennell PB, Privitera M, Loring DW; NEAD Study Group. Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs. N Engl J Med. 2009 Apr 16;360(16):1597-605.


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