Women with epilepsy can become pregnant, have normal children, and participate fully in parenthood. Pregnancies may be higher risk for women with epilepsy, because of the possibility of problems from seizures during pregnancy and because of effects of antiepileptic drugs (AEDs) on the fetus. The Epilepsy Therapy Project has had a special interest in this issue, and a few years ago established the Health Outcomes in Pregnancy and Epilepsy (HOPE) Forum with nine international working groups to identify important unanswered questions regarding epilepsy and pregnancy. Many questions remain, but enough is known to provide useful advice in several areas.
Planning: About half of pregnancies in the US are unplanned, but it is better for a woman with epilepsy to plan and prepare for pregnancy. Changing AEDs in the midst of a pregnancy can be problematic. If a woman has been seizure-free for 2-5 years, and does not have an ongoing condition predisposing to seizures, then it might be possible to eliminate seizure medicines prior to pregnancy. Short of removing all seizure medicines, streamlining to a few of the newer medicines, with lower birth defect risks, may be desirable. A period of at least six months before pregnancy is optimal to adjust medications. Certain seizures are very minor and may allow medication tapering for pregnancy; however, this requires caution, because more powerful seizures can emerge after tapering or reducing AEDs.
Fertility: Women with epilepsy have a slightly lower fertility rate than average. An irregular menstrual cycle and certain hormonal disorders, such as the condition called polycystic ovaries, can be caused both by seizures and by antiepileptic medications, especially Depakote (valproic acid). The desire to engage in sex (libido) can be reduced in association with epilepsy and also by AEDs. The rate of miscarriages is higher in women with epilepsy. Despite these risk factors, the large majority of women with epilepsy can become pregnant and carry the baby successfully to term.
Effect on contraception: The older seizure medicines, Dilantin, phenobarbital, Tegretol, and to a smaller extent other AEDs, can cause birth control pills, patches or injections to become less effective by inducing the liver to eliminate hormones faster from the bloodstream. This can result in unexpected pregnancy. Oral contraceptives containing the equivalent of 35 micrograms or less of the female hormone ethinyl estradiol are particularly likely to be rendered less effective by AEDs. AEDs do not affect efficacy of condoms, foams, IUDs or tubal ligation.
Birth defect risk: Birth defects occur at a rate a few percent higher in women with epilepsy than in the general population. The baseline rate of birth defects, large or small, is about 2% for American women. This birth defect risk increases to about 3-15% among women with epilepsy. Looked at positively, more than 90% of women will have healthy babies. Some contribution to the birth defect risk is made by seizures, and by underlying general health problems, but the main birth defect risk is from antiepileptic medications. This is known because birth defect risk is higher in women taking AEDs for conditions other than epilepsy. Risks are higher with consumption of multiple AEDs during pregnancy (polytherapy), compared to one (monotherapy).
The best AED to use during pregnancy has been debated, but no scientific study specifies a “safest” AED. There is, however, a growing belief that phenobarbital and valproic acid (Depakote) should used with special caution during pregnancy. The US Food and Drug Administration (FDA) categorizes all medicines with respect to safety during pregnancy: A = has good evidence of safety during pregnancy; B = safety in animal studies; C = problems in animal studies, with uncertainty in humans; D = known to cause birth defects in humans, but benefits may outweigh risks; X = known to cause birth defects in humans, and benefits are unlikely to outweigh risks. The older AEDs, for example, Dilantin, phenobarbital, Tegretol, Depakote, are category D. The newer AEDs, for example, Neurontin, Lamictal, Topamax, Zonegran, Trileptal, Keppra, Lyrica, Vimpat, are category C.
Birth defects can cause a wide range of problems in the baby. Phenytoin (Dilantin) and barbiturates can cause cleft lip or palate, or other skull, face, or heart malformations. Valproic acid (Depakote) and, to a smaller extent carbamazepine (Tegretol, Carbatrol), are linked to open spine problems. Carbamazepine can cause “minor defects,” such as fingernail malformations, or mild facial feature distortions, that often resolve by age five years. Phenobarbital or valproate (Depakote) during pregnancy may affect future intelligence of the child, but this can occur with other AEDs as well. Many other birth defects are possible. The best rule is to use the single medicine that is most effective in treating the woman's seizures, but with some bias toward the newer FDA category C antiepileptic drugs.
Folic acid: Supplementation with the vitamin folic acid (folate) 0.4-1.0 mg per day reduces risk for open-spine birth defects among populations of women without neurological disease. By analogy, most epilepsy doctors prescribe folic acid for women who might become pregnant while on antiepileptic medications. The best dose is not known, but quantities range from 0.4 - 5 mg per day. Most over-the-counter daily vitamins contain 0.4 mg (400 micrograms) of folic acid, and most prenatal vitamins, 1 mg. Folic acid usually produces no side effects but in high doses can lead to gastrointestinal or sleep problems, and a few researchers have speculated about heart or cancer problems for very high doses of folic acid. Women of child-bearing potential should take folic acid every day, since many women are not aware that they are pregnant during the critical first six weeks
What to do during pregnancy: During pregnancy, women should be followed by their physicians, at best involving joint management by an obstetrician and a neurologist with expertise in epilepsy. DO NOT stop or change your seizure medications on your own – serious problems can result for you and the future baby. Occasionally, seizures may increase during pregnancy, but they are just as likely to improve or remain stable. During pregnancy, AED blood levels may change in a way to produce unexpected breakthrough seizures or medication side effects, and this should be monitored. Lamictal (lamotrigine) blood levels, for example, can decrease by more than half during pregnancy and increase within two weeks of delivery, if dose is not adjusted as needed. Decreased blood levels also can occur with Keppra, Trileptal and sometimes other AEDs. The usual pregnancy safety concerns also apply, such as good diet, judicious exercise, using only necessary medications, and avoiding alcohol and smoking. Obstetricians usually advise women to take their AEDs up to time of delivery. Seizures during delivery are rare, but if they occur, they can be treated by the usual medical methods.
Pregnancy registries: Several pregnancy registries track safety of AEDs. Participation is free and the registry will both provide you with information and help the epilepsy community to better understand the safety of AEDs during pregnancy. We recommend that you contact one of the registries if you have epilepsy and are pregnant. A list and links can be found at http://my.epilepsy.com/node/572 . These include:
Bleeding and vitamin K: Some of the seizure medications, for example, Dilantin, Tegretol or, phenobarbital, can cause the liver to metabolize blood clotting factors faster, leading to a bleeding tendency in the baby. This can be counteracted by vitamin K, so some doctors prescribe Mephyton (Vitamin K) 5 mg pills, two pills per day for the final month of pregnancy. However, no large scientific study has validated this practice. Babies usually receive a vitamin K injection after birth. .
Breastfeeding: Breastfeeding is beneficial, and the benefits usually outweigh the risks from trace amounts of seizure medicine present in the breast milk. The mother should recognize that the child already has been exposed for nine months to the medicine in the placental bloodstream. AEDs that are highly bound to blood proteins, including Dilantin, phenobarbital, Tegretol and Depakote do not significantly travel into breast milk; others, for example Keppra, Mysoline and Zonegran, do have measurable concentrations in breast milk. Rarely, a child may have side effects such as drowsiness or failure to thrive from seizure medications in breast milk, and then should be switched to formula feedings.
Caring for the baby: If a mother's seizures are not in control, special care should be taken to avoid injury to the baby during lapses of attention. Change the baby's diaper on the floor. Do not leave a baby in bathwater, on heights, near heat or other dangerous objects or chemicals. Find a safe method to carry the baby. Do not drive, with or without the baby, if your seizures are uncontrolled and may affect safety on the road.
Will the baby have epilepsy? Most children of mothers or fathers with epilepsy do not develop epilepsy, although the risk is slightly higher. A child in the general population has about a 1% risk of developing epilepsy. Children of mothers with epilepsy have a 3-9% risk, while children of fathers have a 1.5-3% risk. Still, the actual risk depends upon the specific type of epilepsy. Women with the category of epilepsy called primary generalized (with absence, initially generalized tonic-clonic and myoclonic seizures) are more likely to have children with epilepsy than are those with partial (focal) seizures.
Conclusion: Most women with epilepsy can become pregnant, carry a child successfully through pregnancy, breastfeed and be terrific mothers. For a minority of women with severe and uncontrolled seizures, or major accompanying medical problems, having children may be a poor decision. Planning is key, since medication changes during pregnancy can be risky. Folic acid should be taken by all women who may become pregnant. Some of the antiepileptic drugs can make hormonal contraceptives less effective. During pregnancy, keep in close touch with your doctor and do not change medications on your own. Here are some general suggestions regarding epilepsy and pregnancy, but take specific action based upon consultation with your personal medical team.
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