What's New for Women With Epilepsy?

Birth defects related to use of antiepileptic drugs (AED) have been a topic of concern for many years. I attended a session at a recent conference but was disappointed at the quality of reports. All the studies included very few women, and had inadequate information about the mother, child, AED levels, and other details of the pregnancy, including use of folate vitamins around the time of conception. Unfortunately, no group has collected adequate information from a large enough number of pregnancies to answer the question of what we need to know about AEDs taken by women who are pregnant or who are of childbearing age. Dr. Kimford Meador and colleagues calculated the need for information from at least 500 women taking a single AED through their pregnancies to learn about the effects of that AED. That means we need several thousand women taking different single AEDs during pregnancy to fully understand the types of risks related to each AED. We have exceedingly few data to know whether newer AEDs are better for use during pregnancy.

We also need long-term observation of children born to women taken single AEDs to understand whether the exposure has affected them. This is a particularly difficult type of assessment because of potential genetic factors related to the child’s development. Remembering that a child often grows to an average of the parents' intelligence and height, researchers need extensive information about both parents. “The acorn does not fall far from the tree.” These studies also require detailed cognitive assessments of the child and parents, information about other medical disorders, as well as long-term follow-up. Children with some developmental delays may still have full cognitive and physical capacity in later years. Small acorns might still produce great oak trees, given appropriate environmental conditions.

Some studies are confounded by including women who took multiple AEDs at conception or the first trimester. There also are reports that some AEDs have greater potential for minor birth defects. I wonder whether patients with specific seizure types are preferentially prescribed certain AEDs, leading to more data from women who have that type? Are the differences in acorns associated with rainfall or with the genetic strain of the parent tree?

For example, valproate is likely to be the treatment of choice for women with JME or other genetically related epilepsies. Thus, all children have some of her genetic risks no matter what AED their mother used during pregnancy. A recent study noted that much of the birth defect risk is attributable to the AEDs, since the risks were present for women who used the drugs for reasons other than epilepsy. This is the question unanswered by all the current pregnancy registries, leaving us without adequate data to parse out what effects are related to drug and what effects are related to epilepsy.

The Epilepsy Therapy Project organized a review of the problems in assessing use of AEDs during pregnancy: Health Outcomes in Pregnancy in Epilepsy (HOPE). All the articles are available on the Web at http://professionals.epilepsy.com/page/ar_1191430420.html.

Among the unanswered questions is the extent to which AEDs may be related to birth defects and their degree of interaction with genotype. Definition of whether it is the AEDs or the epilepsy (or other factors) leading to developmental delays in children is a question of gene-by-environment interaction. We need extensive phenotypic and genotypic data to reveal reasons for anatomic and behavioral effects of AEDs.

While doctors wait for the science to catch up with the questions, the Epilepsy Therapy Project offers a review of hormonal issues from menarche through menopause. The Website http://professionals.epilepsy.com provides a downloadable worksheet that doctors and nurses may use to review issues with patients and may be placed in the chart as documentation of the discussion (http://professionals.epilepsy.com/page/women_checklist.html). A full review of the topics is also provided to prepare doctors, nurses, and other healthcare providers to answer patient questions.

Epilepsy Therapy Project acted when no other group took the lead on dissecting some of the issues related to data emerging from the current pregnancy registries. We can do this because we have no bureaucracy – we just do what’s needed. Now it’s your turn to act by sending a donation based on the amount of value you get from reading epilepsy.com and http://professionals.epilepsy.com.

We need your support to maintain our websites.

Thank you,

Joyce Cramer
President, Epilepsy Therapy Project

References

1. Meador KJ, Pennell PB, Harden CL, et al., for the HOPE Work Group. Pregnancy registries in epilepsy: a consensus statement on health outcomes. Neurology. 2008;71:1109-1117.
2. Meador KJ. Baker G. Cohen MJ. et al. Cognitive/behavioral teratogenetic effects of antiepileptic drugs. Epilepsy Behav. 2007;11:292-302.
3. Cramer JA, Gordon J, Schachter S, Devinsky O, and the Epilepsy Therapy Development Project Women's Issues Work Group. Women with epilepsy: hormonal issues from menarche through menopause. Epilepsy Behav. 2007;11:160-178.