Major congenital malformations in children of women with epilepsy

• The risk of major malformations (MCM) is increased with antiepileptic drug exposure.
• The risk of MCM is greater with valproate than other commonly used antiepileptics.
• The risk of MCM increases with the dose of the antiepileptic drug in early pregnancy.
• The risk is increased for women with infants with MCM from previous pregnancy.

It has been long known that the risk of major congenital malformations is increased among children of mothers with epilepsy. This is mainly due to the teratogenic effects of antiepileptic drugs although other factors, such as genetically determined individual susceptibility, are likely to contribute. Recent large scale prospective epilepsy and pregnancy registries have indicated that the rate of major congenital malformations may be at most two-fold higher than expected with exposure in utero to the presently most frequently used antiepileptic drugs such as carbamazepine or lamotrigine. Higher rates are consistently reported with exposure to valproate. The risk of teratogenic effects appears to be dose dependent and the lowest effective dose should thus be established before pregnancy regardless of which antiepileptic drug the woman is taking. Major changes such as switches between drugs should be avoided when pregnancy is established.