Published article: Meador KJ, Pennell PB, Harden CL, Gordon JC, Tomson T, Kaplan PW, Holmes GL, French JA, Hauser WA, Wells PG, Cramer JA and HOPE Work Group Collaborators. Pregnancy registries in epilepsy: a consensus statement on health outcomes. Neurology. 2008;71:1109-17.

The Epilepsy Therapy Project established the HOPE group, standing for Health Outcomes in Pregnancy and Epilepsy, comprising nine international groups with input from six pregnancy registries. A consensus view of HOPE was published in the September, 2008 issue of the journal Neurology. The article points out that about 25,000 children are born each year to women with epilepsy. Most children are born normal, but about 4.5% born to women taking one antiepileptic drug (AED) have a birth defect. This compares to 8.1% for women taking more than one AED and to a background population birth defect rate of 1.6-2.1%. Birth defects can include minor or sometimes major problems with heart, face, fingers, genitals, bones or brain. Much of the increased risk for birth defects in children of women with epilepsy comes from effects of AEDs on the fetus. However, women with epilepsy should not stop their AEDs before or during pregnancy, without having detailed discussions with their seizure doctor and obstetrician. Stopping AEDs can lead to uncontrolled seizures, which can be harmful to both the mother and the future baby. The article recommends using the minimum amount of and smallest number of medications that is still therapeutic and able to control serious seizures.

It is hard to specify a single “best” AED during pregnancy. The article reviews data collected from six pregnancy registries, with over 20,000 enrolled pregnancies. Because the groups using one drug versus another are not always comparable in terms of seizure characteristics and other health factors, registries only give clues to problem drugs, not proof. Treatment with valproic acid (Depakote™) or phenobarbital during pregnancy appeared potentially problematic. The malformation rate with valproate varied in different registries from 6.2 - 13.3%. The rate with phenobarbital was approximately 6% for malformations, but an earlier study suggested additional risk for lower intelligence in the offspring when phenobarbital was used during pregnancy. Malformation rates with carbamazepine (Tegretol™, Carbatrol™) ranged from 2.2 -4.0%, and with lamotrigine (Lamictal™) from 1.4 - 3.2%. Individual cases of cleft lip and cleft palate occurred with carbamazepine or lamotrigine. Numbers of pregnancies with single drug therapy with other AEDs was too low for firm conclusions.

Although not part of the article, it is worth remembering this: women with epilepsy who are planning to have children should plan ahead and optimize medications before pregnancy. Potential mothers should confer with their doctors about taking folic acid (folate), a vitamin that may reduce the risk for birth defects.

Additional resources:

• Women's Checklist for Discussions With Your Doctor
• Health Outcomes in Pregnancy and Epilepsy (HOPE)
• Additional information on HOPE

By Robert Fisher, M.D., Ph.D.