In the past, women with epilepsy were sometimes discouraged from having children because physicians worried about dangers to both child and mother. In 1998, the AAN published a series of guidelines for women with epilepsy who wanted to become pregnant. On April 27, the AAN released updated recommendations to address new data and new drugs. The guidelines appeared online in advance of the print edition of Neurology.
Cynthia L. Harden, MD, professor of neurology and director of the Epilepsy Division at the University of Miami Miller School of Medicine, spoke to Neurology Today about what the guidelines mean for managing women with epilepsy. Dr. Harden was lead author of the new guidelines.
WHY COME UP WITH NEW GUIDELINES?
This is an update of the guidelines published in 1998. Since then the AAN has developed a critical way of evaluating scientific evidence to figure out which scientific information is true and unbiased about a controversial and emotional topic. After 1998, multiple registries were tracking pregnant women who were exposed to anti-seizure medication. That gave us a lot of new information, and we were able to use the new data to get closer to the truth of what the risks are for women.
WHAT IS THE MAJOR CHANGE FROM THE 1998 GUIDELINES?
The most important change is the warning about valproate, which is riskier than other anti-seizure medications. It's not the most commonly prescribed, but it's one of the more frequently used, particularly outside the US. It's also used for migraine prevention.
WHAT ARE THE ADVERSE RISKS THAT HAVE OCCURRED TO PEOPLE TAKING VALPROATE?
Taking this drug during the first three months of pregnancy resulted in more birth defects and increased the chance that the child would have impaired cognitive development. We don't know how use of this drug increased these problems. It remains an area that needs more research.
WERE THERE OTHER RISKS FOR WOMEN WITH EPILEPSY?
It was interesting that there were not many increased risks for obstetrical outcomes, including C-sections. We didn't find an increased risk for premature labor and delivery — there were a lot of reassuring outcomes.
IS THERE ANYTHING THAT WOMEN WITH EPILEPSY NEED TO WATCH DURING PREGNANCY?
Some changes occur with pregnancy, the most significant being that blood levels of the drug decline. Medicines clear through the kidneys more efficiently and the blood levels decline, so that could increase the risk of having a seizure. Women need to work with their physicians to have blood levels checked frequently.
WERE THERE ANY CHANGES IN OTHER MEDICATIONS THAT RAISED RED FLAGS?
There were also risks for women who were taking more than one anti-seizure medication. Most people are taking only one medication and they're doing fine, but others are taking more than one antiepileptic drug (AED), and they need to work with their doctors to try and get down to one AED.
SO SHOULD WOMEN ON MORE THAN ONE AED DROP DOWN TO ONE MEDICATION? IS THAT THE GENERAL PRACTICE?
The aim of treatment is to take the fewest medications at the lowest effective dose. There should definitely be a discussion between the patient and her doctor about trying to be seizure-free on one medication instead of more than one.
WHAT ABOUT SUPPLEMENTS?
Some evidence found that folic acid was helpful in preventing birth defects. And there was no evidence regarding the taking of Vitamin K during pregnancy, so we cannot comment on this.
WHAT DOES THIS MEAN FOR CLINICIANS?
There are three main points: (1) Avoid valproate. (2) Avoid prescribing more than one AED for women with epilepsy. (3) Be supportive. Overall, women who had no seizures in the nine months before pregnancy were seizure free during pregnancy and were at low-risk for complications. Be proactive in checking the drug blood levels during pregnancy. We didn't specify how often to check in the guidelines but, depending on the drug, every four to eight weeks or even more frequently is recommended for lamotrigine.
WHAT'S THE GREATEST WORRY HERE?
There's a danger that women will just stop taking their medications. That increases the risk of a seizure. The study was reassuring in finding that only one medicine, valproate, was clearly associated with increased risk.
SO, BARRING THE ONE MEDICATION WARNING, WHAT IS THE GENERAL FINDING?
Overall, pregnancy appears safe and shouldn't be discouraged. I've had so many patients — women who are well and controlled by medication — tell me that they've been told that, because of the epilepsy, they shouldn't have children. Hopefully these guidelines stop that kind of dialogue.
• Practice Parameter update: Management issues for women with epilepsy—focus on pregnancy (an evidence-based review): Vitamin K, folic acid, blood levels, and breastfeeding. Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Harden CL, Pennel CP, Le Guen C, et al. Neurology 2009; E-pub 2009 April 27.
• Practice Parameter update: Management issues for women with epilepsy—Focus on pregnancy (an evidence-based review): Teratogenesis and perinatal outcomes. Report of the Quality Standards Subcommittee and Therapeutics and Technology Subcommittee of the American Academy of Neurology and American Epilepsy Society. Harden CL, Meador KJ, Le Guen C, et al. Neurology 2009; E-pub 2009 April 27.
• Practice Parameter update: Management issues for women with epilepsy—focus on pregnancy (an evidence-based review): Obstetrical complications and change in seizure frequency. Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Harden CL, Hopp J, Le Guen C, et al. Neurology 2009; E-pub 2009 April 27.