When to Discontinue Anticonvulsants in Pregnancy : Lack of neurologic abnormalities, normal EEG, onset of epilepsy in childhood bode well for stopping the drugs.


SAN FRANCISCO — Anticonvulsants are known to cause birth defects when taken during pregnancy, but physicians should weigh the benefits and risks before discontinuing anticonvulsant therapy, Jennifer R. Niebyl, M.D., said at the annual meeting of the American College of Obstetricians and Gynecologists.

The risks are not all that large, said Dr. Niebyl of the University of Iowa, Iowa City. Only 5%–10% of women taking anticonvulsants during pregnancy develop fetal hydantoin syndrome.

Women taking a single anticonvulsant medication have about 2.5 times the risk of having this embryopathy as do epileptic women not taking anticonvulsants. Those taking at least two anticonvulsants have a significantly higher risk: 3.7 times as high as epileptics not taking anticonvulsants. This suggests it is the drug, not the epilepsy itself, that causes the syndrome.

Children with fetal hydantoin syndrome typically show multiple symptoms, including disorders of growth and of mental development, dysmorphic craniofacial features, and hypoplasia of the nails and distal phalanges.

Dr. Niebyl said it's becoming clear that it's desirable to wean women planning a pregnancy from their anticonvulsant medications if possible. This is more likely to be successful in women whose epilepsy is idiopathic, rather than caused by a head injury.

Other factors that bode well for getting women off anticonvulsants include a lack of neurologic abnormalities, a normal EEG, onset of epilepsy in childhood, seizures controlled by a single drug, and being seizure free for at least 2 years.

About 75% of these women will remain seizure free after discontinuing medication. But since 25% will have a seizure—and it's impossible to predict who will fall into that group—these women should be instructed not to drive during the time they're off the drug.

“If you don't see the patient until they're already pregnant, the benefits of continuing therapy usually outweigh the risks,” Dr. Niebyl said.

Anticonvulsants can interfere with folate metabolism, so Dr. Niebyl recommended being especially vigilant about folic acid supplementation. And some of these drugs—particularly phenytoin, primidone (Mysoline), and phenobarbital—inhibit the transfer of vitamin K across the placenta. This results in a decrease in fetal clotting factors and an increase in the risk of fetal hemorrhage. For this reason, many physicians will put patients on vitamin K supplementation (20 mg/day) for the final month or two of pregnancy, although there's no definitive evidence that this has a beneficial effect.

Some of the newer anticonvulsant medications, such as lamotrigine (Lamictal), may confer a smaller risk of birth defects than the older drugs, Dr. Niebyl said, but once again definitive evidence is lacking.

Dr. Niebyl said she had no financial conflicts of interest relevant to her presentation.

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