Antiepileptics in the Womb: Effects on Cognition

Andrew N. Wilner, MD; Kimford J. Meador, MD


February 14, 2012

Editor's note:

At the American Epilepsy Society's 65th Annual Meeting, held in Baltimore, Maryland, December 2-4, 2011, Medscape contributor Andrew N. Wilner, MD, interviewed Kimford Meador, MD, Professor of Neurology at Emory University, Atlanta, Georgia, on new 6-year data on the potential cognitive effects of in utero antiepileptic exposure.

Antiepileptics and Cognition: Introduction

Dr. Wilner: Hello, Dr. Meador. At this meeting, you presented 6-year data on 4 antiepileptic drugs.[1] What were the highlights of your presentation?

Dr. Meador: Our study was a prospective observational study looking at cognitive outcomes in children exposed to antiepileptic drugs. We found that children exposed to valproate exhibited significantly lower IQs compared with children exposed to carbamazepine, lamotrigine, or phenytoin. We also saw that this was a dose-dependent effect for valproate. We didn't see a dose-dependent effect for any other drug. Valproate also interfered with the relationship of the mother's IQ to the child's IQ, which is a very strong relationship that we saw with all the other drugs but was not seen in the valproate group.

In addition, we saw that the effect of valproate was worse for verbal than nonverbal abilities, and that the valproate affected the verbal abilities more than the other 3 drugs. We also saw a worse effect for verbal performance over nonverbal performance across all the drugs, but this was driven by primarily by valproate and to some extent by lamotrigine.

The results across all the drugs should be interpreted with caution, as this finding needs to be reproduced in another cohort. In contrast, the cognitive effects of valproate have been seen in other cohorts, and the US Food and Drug Administration (FDA) has added an extra warning for valproate in the United States. I believe that this is a true finding, suggesting that this drug is associated with increased risks for poor cognitive outcome in children exposed during pregnancy.

Dr. Wilner: Could the differential between verbal and nonverbal deficits be due to the fact that it's easier to measure verbal deficits?

Dr. Meador: These are scaled scores, so they should be equal in the general population, which they are. But here, they're not.


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