Teratogenicity of antiepileptic drugs: state of the art

Information on the risks associated with antiepileptic drug (AED) use in pregnancy is necessary for a rational approach to the management of women of childbearing potential who have epilepsy. This reviews addresses recent reports on the risk for birth defects and impaired postnatal development attributable to prenatal exposure to AEDs.

Some studies have indicated greater risk for birth defects as well as for lower verbal IQ in association with exposure to valproic acid, as compared with some other AEDs. The risk appears to be greater at doses above 800-1000 mg/day; lower doses may not carry higher risks than those associated with other AEDs. This observation is a cause of concern but more data are needed from prospective studies to assess the possible impact of confounding factors in order to clarify whether there is a causal relationship. Large-scale pregnancy registries have been launched and are expected to provide more conclusive comparative data on the most frequently used AEDs in the near future.

Although further studies are needed, it appears reasonable to use valproic acid with caution in women with epilepsy who are planning to become pregnant, and to consider prescribing other equally effective and safer AEDs if they are available. The importance of seizure control during pregnancy must not be neglected, and any attempt to change treatment should be done before conception. Drug withdrawal during pregnancy should be avoided, and patients should be made aware that definitive evidence on the relative safety of AEDs is lacking.