Epilepsy - Outlook and Effects

Epilepsy and Pregnancy

Studies have been conflicting on the effects of fertility from epilepsy, but most suggest that fertility rates among women with epilepsy are lower than among women in the general population. A number of factors, including anti-epileptic drugs (AEDs) or social factors, such as marriage at an older age, may contribute to this lower rate. Certain AEDs, particularly valproate, disrupt ovulation and menstruation by increasing male hormone levels and weight and causing polycystic ovaries.

Effects of Epilepsy on the Pregnant Patient and the Fetus

In women who become pregnant, there is a risk for uncontrolled seizures and birth defects from antiseizure medications. In studies of women who were carefully monitored, however, 95% of pregnancies (which is close to normal) had favorable outcomes.

Effects of Seizures. Isolated seizures do not appear to pose any adverse effects to the mother or the unborn child, but repeated seizures and status epilepticus can lead to great dangers. In one study, the effect of epilepsy on complications during pregnancy was the same as in non-epileptic women except for a higher rate of premature deliveries (8.2% in the women with epilepsy).

Effects of Medications on the Fetus. All standard antiseizure drugs pose a significant risk for birth defects, which include malformations of the face and hands or more serious effects on the heart or mental development. The more medications required the higher the risk. (Epilepsy itself, however, does not appear to pose any higher risk for birth defects in the child.) Pregnant women who need to continue medication should be on the lowest possible dose of a single type of drug, if feasible.

Effect of Pregnancy on Seizure Frequency

The frequency and intensity of seizures vary widely in women with epilepsy. About 25% of pregnant women with epilepsy face an increase in events, and the risk is highest in those who have more than one seizure per month prior to becoming pregnant. In most cases, however, there is no change at all. Some pregnant women even have a decrease in seizures. The risk is lower in women who experience less than one seizure in the 9 months prior to becoming pregnant. The following conditions may contribute to an increase in seizures during pregnancy:

• Nausea and vomiting (vitamin B6 and antihistamines may help with nausea)
• Fluid retention
• Higher estrogen levels
• Psychological and emotional stress
• Medication noncompliance from fear of side effects
• Problems with sleeping
• Changes in absorption of anticonvulsants

Steps for Women Who Want to Become Pregnant

• A woman who wishes to become pregnant and has been seizure-free for 2 or more years may attempt to discontinue drugs under her doctor’s supervision.
• If she has not been seizure-free, she should continue medications but try to reduce them to a single drug, if possible. (Again under a doctor’s supervision.)

Steps During Unplanned Pregnancy

• If a woman taking antiseizure medications has an unplanned pregnancy, there may be no point in switching medications right away, since the effects of the drugs last for 10 weeks. However, she should notify her doctor immediately.
• She should be carefully monitored for both drug levels and any abnormalities in the fetus. Ideally, drug levels should be measured every one or two months or more often if seizures are not controlled. Dosage levels should be adjusted accordingly.
• She should also be carefully monitored with ultrasonic evaluation and amniocentesis (visual tests and examination of the fluid in the womb for birth defects and other fetal problems).

Drugs Used During Pregnancy

Some types of anti-epileptic drugs (AEDs) can increase the risks for birth defects, especially when taken during the first trimester of pregnancy. Expert guidelines advise that pregnant women use the most effective medication for their type of epilepsy at the lowest dose possible to control seizures. They should also have their doctors take blood tests during pregnancy to monitor their drug levels.

A 2006 study compared the chances of fetal death or serious birth defects for four commonly prescribed AEDs. The risk was significantly higher for valproate than the other drugs. (Birth defects included skull and limb deformities, and brain, heart, and lung problems.) In this study of 333 mother-child pairs, the following percentages of pregnancies resulted in birth defects depending on drug used:

• Valproate (20.3%)
• Phenytoin (10.7%)
• Carbamazepine (8.2%)
• Lamotrigine (1.0%)

This study was small, and included only a few types of AEDs. In general, research indicates that 90% of women who take AEDs will give birth to healthy children. Still, doctors recommend that women of child-bearing age use a drug other than valproate if possible.

The risk for malformation is higher when more medications are used. For example, there is a 3% risk of birth defects with women who use one anticonvulsant. The risk increases to 20% when four drugs are used.

Birth Defects Associated with Medication. The most common birth defects related to anti-epileptic drugs are:

• Cleft lip or palate (risks from lamotrigine, phenobarbital, phenytoin, valproate especially when taken during first trimester)
• Genital or urinary abnormalities (risk from most standard drugs)
• Neural tube defects (NTD) in the skull or spinal column (risk of 2% with valproate and 1% with carbamazepine). These complications are most often due to lower folic acid levels caused by both pregnancy itself and antiseizure drugs. Supplements can help prevent this problem. Folic acid is recommended for all pregnant women, in any case, and women with epilepsy should talk with their doctor about taking a supplement of folic acid (5 mg) at least 3 months before conception as well as during the first trimester.
• Mental impairment (known risk with phenytoin and valproate; inconclusive in carbamazepine and phenobarbital)
• Heart defects (risk from phenobarbital, phenytoin, valproate)
• Many antiseizure drugs also cause a deficiency in vitamin K clotting factors that increases the risk for hemorrhage in the newborn. Treatment with vitamin K during the last month of pregnancy and a single dose given to the newborn is recommended.

Labor and Delivery

Seizures occur during labor and after delivery in a small percentage of women with epilepsy. The following labor complications are more common among pregnant women with epilepsy: Vaginal bleeding, anemia, and preeclampsia (extremely high blood pressure in the third trimester). If seizures occur during labor, they are generally treated intravenously with benzodiazepines or phenytoin. If tonic-clonic seizures, absence seizures, or status epilepticus occur, a cesarean section may be appropriate.

Postnatal Care

Monitoring the Infant. The infant should be thoroughly examined for any birth defects. Also, if the mother was given phenobarbital or primidone while pregnant, the infant should be monitored for up to 8 months to see if withdrawal symptoms develop. Drug dosages will also need to be adjusted for the mother after delivery.

Breastfeeding. Women on most AEDs can usually nurse their babies, since usually only a small amount of the drug enters the breast milk. The lowest levels are with phenytoin and valproate. (Ethosuximide and possibly levetiracetam are exceptions and should be avoided when a woman is breastfeeding. Women taking phenobarbital are also usually advised not to nurse.) A mother should watch for signs of lethargy or extreme sleepiness in her infant, which could be caused by her medication.