By Joanne B. Rogin, M.D.

Epilepsy is one of the most common medical conditions in women of reproductive age. It has been estimated that more than 1.1 million women with epilepsy in the United States are of childbearing age. With a birth rate of 3-5 per 1000 births, approximately 24,000 babies are born to women with epilepsy each year. Women with epilepsy have a number of unique concerns during pregnancy. Nevertheless, the overwhelming majority of these women will have a normal baby and the pregnancy will not significantly affect their epilepsy. Utilizing strategies to minimize the risk will promote a good outcome for mother and baby.

Seizure frequency during pregnancy

Seizure frequency fortunately declines or remains the same in the majority of women during pregnancy. In 15% to 30% of women, however, there may be an increase in seizure frequency, most often in the first or third trimester. The increased seizure frequency is not predictable by the type of seizures the woman has, how long she has had epilepsy, or even the presence of seizures in a previous pregnancy. Even having catamenial epilepsy, seizures occurring with the menstrual cycle, does not predict whether the woman will have more seizures during pregnancy. A number of factors have been suggested as possible triggers for these seizures, including hormone changes, water and sodium retention, stress, and decreasing blood levels of antiepileptic medications. Inadequate sleep and not taking medications as prescribed may be the most important factors that women with epilepsy can control, along with consulting her neurologist during this time.

Risks from seizures and from anti-epileptic drugs

Both seizures and medications are associated with some risks. The risk of seizures is associated with seizure type. Partial seizures probably do not carry as much risk but they may become generalized seizures, and generalized tonic-clonic seizures are associated with increased risk to both the mother and baby. These risks include trauma from falls or burns, increased risk of premature labor, miscarriages, and fetal heart rate suppression. Seizure control is necessary because the risks from seizures are felt by epileptologists to be greater than the risks from medications, which may be minimized by utilizing specific strategies.

The risk to the developing baby from anti-epileptic drugs taken during pregnancy is primarily that of congenital malformation or birth defects. In the general population, there is a 2% to 3% occurrence of congenital malformations that cannot always be predicted or prevented. In women with epilepsy, the risk is doubled to about 4% to 6%, but overall remains low. There is an increased risk with using polytherapy, more than one type of medication, and with a higher dose of medication. There clearly is a genetic role, with a previous pregnancy or family history of a congenital malformation raising the risk during the current pregnancy. Genetic counseling is needed in this circumstance. The most common malformations include cleft lip and clef palate, which most often can be corrected surgically. Cardiac and urogenital defects also occur. Research is ongoing concerning the risks for developmental delays.

There is limited information available on our new anti-epileptic drugs and only slightly more on the classic anti-epileptic drugs. Given available information, it is recommended that the most effective drug with the fewest side effects be used. Pregnancy registries have been established to help gain information. All pregnant women with epilepsy are encouraged to enroll in the North American Anti-Epileptic Drug Pregnancy Registry by calling 1-888-233-2334 prior to having the initial pregnancy screening to help add to our knowledge base. Women outside North America are encouraged to enroll in their pregnancy registry via their neurologist.

While most of our anti-epileptic drugs can be and are used safely, some carry increased specific risks. Valproate used in the first 28 days of pregnancy carries a 1% to 2% risk of neural tube defects or lack of spinal cord closure. In the general population, this risk is decreased by taking folate at the time of neural tube closure early in the first trimester. Although it may not be as protective in women with epilepsy, folate should be taken daily prior to becoming pregnant since most women do not know they are pregnant until after the time of neural tube closure (24-28 days after conception). A daily multivitamin containing 0.4 mg folate, as well as an additional 1- to 4-mg folate supplement, is recommended for all women of childbearing age. Selenium and zinc, contained in a multivitamin with minerals, also may be of some benefit. Vitamin K1 should be taken the last month of pregnancy to prevent rare bleeding complications in the newborn.

Strategies to minimize risks

Most importantly, women should get accurate information prior to and during pregnancy. If anti-epileptic drugs are not needed, multiple medications are being taken, or medications are given at high dosages, changes should be considered with a neurologist prior to a planned pregnancy. The lowest possible anti-epileptic drug dose that will continue to maintain seizure control is recommended. Being on a single drug, monotherapy, will decrease the risk of birth defects and result in fewer drug interactions, fewer side effects, and improve compliance.

Monitoring drug levels is also very important. Anti-epileptic drug levels should be checked throughout the pregnancy and following delivery. The levels of all anti-epileptic drugs decline during pregnancy, with some being more affected than others. Dosage adjustments may be needed. Since the levels then rise following delivery, monitoring in the post-partum period is also needed to minimize side effects. Monitoring the baby with maternal serum-alpha-fetoprotein testing and a high resolution or level II ultrasound should be performed by the obstetrician. Epilepsy is not an indication alone for a cesarean section, and most women deliver vaginally.

While the anti-epileptic drugs are present in breast milk, breastfeeding is encouraged. Breastfeeding can generally be done safely, since the baby has been exposed to the anti-epileptic drugs throughout the pregnancy and the absolute amounts of drug are low. Strategies such as taking the anti-epileptic drugs immediately after a feeding should be considered to minimize the amount of drugs in a feeding. Breastfeeding is generally safe and recommended for its important benefits to the infant. Caring for the baby can also be a concern. Changing diapers on the floor and bathing the infant with other adults present or with a sponge bath are some useful strategies.

Seeing the doctor before becoming pregnant, keeping regular appointments, and checking anti-epileptic drug blood levels during pregnancy are recommended. Taking the appropriate medications as prescribed, as well as having adequate rest and sleep are of utmost importance. Paying attention to nutrition with adequate weight gain and taking a multivitamin and additional folate before, during, and after pregnancy are needed. Avoiding cigarettes, alcohol, and caffeine are important for all women during pregnancy. Keeping all these factors in mind, the overwhelming majority of women with epilepsy will have a normal healthy baby.

• Physician's Discussion Checklist for Women with Epilepsy
• Physician's Discussion Guide for Women with Epilepsy

Dr. Rogin is Medical Director, Midwest Center for Seizure Disorders, Minneapolis Clinic of Neurology and Chair, Professional Advisory Board, Epilepsy Foundation of Minnesota.

Edited by Jacki Gordon, PhD.
Reviewed by Steven C. Schachter, M.D., December 14, 2006.