Valproate, an epilepsy drug also used to treat bipolar disorder, is linked
to lower IQ scores at age 3 in children exposed to the drug before birth than
in children whose mothers took other antiepileptic drugs during pregnancy, a
study published in the April 4 New England Journal of Medicine
From 1999 to 2004, U.S. and U.K. researchers enrolled 303 pregnant women
with epilepsy who were taking lamotrigine, phenytoin, carbamazepine, or
valproate in a prospective, observational study known as the
Neurodevelopmental Effects of Antiepileptic Drugs study. The researchers
conducted follow-up assessments, especially in terms of neurological
development, in the children. Women who were not taking any antiepileptic
drugs during pregnancy were not included.
The average IQ score of 3-year-old children who had in utero exposure to
valproate was 92, which was statistically significantly lower than that of
children exposed to lamotrigine (average IQ 101), phenytoin (99), or
carbamazepine (98). The comparisons among lamotrigine, phenytoin, and
carbamazepine were not statistically different. The authors also found a
dose-dependent relationship between valproate and IQ score.
That valproate exposure carries a higher risk of birth defects than other
antiepileptics, such as lamotrigine and carbamazepine, is not new knowledge,
Torbjorn Tomson, M.D., a professor of clinical neuroscience at the Karolinska
Institute in Sweden, pointed out in an editorial. The worthwhile discovery of
this study was the differential effects on children's long-term cognitive
development associated with various antiepileptics. This was the largest
prospective study so far on the effects of antiepileptics on cognitive
This study was reported in several media outlets, including the New
York Times and the Associated Press, with broad headlines such as"
I.Q. Harmed by Epilepsy Drug in Utero," without clearly
presenting the context that the study was a comparison between valproate and
other antiepileptic drugs.
Untreated epilepsy, as well as untreated bipolar disorder, poses a
significant risk of harm to pregnant women and their fetuses. For many
pregnant patients, stopping medication is not an option. Therefore, accurately
describing the different risks among drugs in the same class is critically
important for physicians and patients. The authors concluded that valproate
should not be used as a first-line treatment for women who are pregnant or may
become pregnant. In addition, "discussion of the risks of valproate
should be balanced with consideration of the risks of uncontrolled
seizures," Tomson recommended.
An abstract of "Cognitive Function at 3 Years of Age After
Fetal Exposure to Antiepileptic Drugs" is posted at<content.nejm.org/cgi/content/short/360/16/1597>.▪