The good news and the bad news on epilepsy drugs for pregnant women

Mar 21 2005

Two new studies on the effects of epilepsy drugs taken during pregnancy show mixed results. The risk of birth defects with a newer drug, lamotrigine, was similar to that in women without epilepsy.

The epilepsy drug valproic acid, or sodium valproate, which has been used for a number of years, was shown to increase the risk of defects at birth. Both studies were published in the March 22 issue of Neurology, the scientific journal of the American Academy of Neurology. Another study found that children ages 6 to 16 who had been exposed to valproic acid during pregnancy had lower verbal IQ scores than children exposed to other epilepsy drugs or no epilepsy drugs during pregnancy.

The results from the study of lamotrigine is good news; lamotrigine is one of several more recent epilepsy drugs introduced after 1990 and few studies have been done on their effect on human foetuses. This study monitored birth defects in lamotrigine-exposed pregnancies reported over more than 11 years in the International Lamotrigine Pregnancy Registry.

Of 414 pregnancies where the foetus was exposed during the first trimester to lamotrigine as the only epilepsy drug used, there were 12 cases of major birth defects. That translates to a 2.9 percent risk of having a birth defect, which is similar to the 2 to 3 percent risk in the general population. That risk increased to 12.5 percent for women who were taking lamotrigine along with valproic acid during the first trimester.

Neurologist Patricia Penovich, MD, of the Minnesota Epilepsy Group PA, in an editorial accompanying the studies, says that though a large number of women took part in the study, the number of pregnancies was too small to give absolute answers but the results are reassuring to women. The importance of controlling seizures with only one epilepsy drug if possible and of planning carefully how epilepsy drugs should used during and before pregnancy was empathised.

The news about the drug valproic acid is of course bad news; one study, which monitored 149 women found there were 16 infants with birth defects or 10.7 percent.The women taking valproic acid were nearly three times more likely to have an infant with a birth defect than women taking another epilepsy drug. They were more than seven times more likely to have an infant with a birth defect than women in the general population.

In the second study on valproic acid, British researchers recruited 163 mothers with epilepsy and their children and gave them a number of tests. A total of 249 children between the ages of 6 and 16 took the tests. The 41 children who were exposed to valproic acid during pregnancy were more likely to have low verbal IQ scores (average of 84) compared to other groups in the study, such as those exposed only to the drug phenytoin (average score of 99) or those not exposed to any epilepsy drug during pregnancy (average score of 92).

Those exposed to valproic acid were also more likely to have overall IQ scores in the extremely low, or mentally impaired, range. Two to three percent of the population would be expected to fall in this range. In the study, 22 percent of those exposed to valproic acid were in this range.

Maintaining effective epilepsy treatment during pregnancy is crucial, seizures can cause fetal distress, and the severe epilepsy state called status epilepticus where attacks occur in rapid succession can cause catastrophic damage to the brain of the foetus; More studies need to be done to understand how valproic acid works to affect foetal development. Dr.Penovich also said that without good animal models, the mechanism for the abnormalities remains unknown.

Diego Wyszynski, MD, PhD, of Boston University School of Medicine and senior epidemiologist with the Antiepileptic Drug Pregnancy Registry says it is very important that physicians and women have as much information as possible about these medications, and that pregnancy registries are really the only way at present to collect data on what medications women are taking and what effects they may be having on their babies.

Women can sign up for the Antiepileptic Drug Pregnancy Registry, which is based at Massachusetts General Hospital, by calling toll-free (888) 233-2334. Women can talk to their doctors about enrolling in the International Lamotrigine Pregnancy Registry.

The International Lamotrigine Pregnancy Registry is funded by GlaxoSmithKline, the manufacturer of lamotrigine.

The Antiepileptic Drug Pregnancy Registry is funded by sponsorship grants received from: Abbott Laboratories, Elan Pharmaceuticals, GlaxoSmithKline, Novartis, Ortho-McNeil, and Pfizer Pharmaceuticals.

The American Academy of Neurology, an association of more than 18,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as epilepsy, dystonia, migraine, Huntington’s disease, and dementia.