IQ in children after fetal exposure to valproate

Cognitive Function at 3 Years of Age after Fetal Exposure to Antiepileptic Drugs

Kimford J. Meador, M.D., Gus A. Baker, Ph.D., Jill Clayton-Smith, M.D., Deborah T. Combs-Cantrell, M.D., Morris Cohen, Ed.D., Laura A. Kalayjian, M.D., Andres Kanner, M.D., Joyce D. Liporace, M.D., Page Pannell, M.D., Michael Privitera, M.D., David W. Loring, Ph.D., for the NEAD Group 

The New England Journal of Medicine, April 16, 2009(NEJM 2009; 360(16):1597-1605) 

The NEJM report on cognitive function in children after fetal exposure to anticonvulsant drugs is an important study because it is the first to demonstrate that lower IQ in children of mothers with epilepsy was associated with mothers receiving the anticonvulsant medication (AED) valproate. 

It has already been established that valproate is not a first line drug for women of child bearing potential because of teratogenesis risk.  We have known that AEDs are associated with a variety of major malformations in children born to mothers receiving AEDs during pregnancy.  However, the question of more subtle cognitive impairment has never been addressed adequately. 

This report on cognitive function is of a unique study with rigorous IQ testing of mother and children. Mothers IQ is the most important determinant of child’s IQ (sorry dads) and older studies that did not measure mother’s IQ are not valid. 

The study found that children born to mothers receiving valproate during pregnancy had IQ 6-9 points lower than other AEDs.  The IQ effect was dose related. None of the other AEDs studied (carbamazepine, phenytoin, lamotrigine) were associated with lower IQ in children. 

This study confirms that valproate is not a first choice drug for treatment of epilepsy in women of child bearing age.  

It must be recognized, however, that seizures are dangerous and pose a significant risk to mother and child.  In unusual circumstances where valproate is the only AED that can control seizures, the lowest effective dose should be used.  The American Epilepsy Society warns further that valproate when used for the woman should not be stopped without consultation with her neurologist. 

Further research is needed into new anticonvulsant medications can completely control seizures and are safe to use during pregnancy.