SEATTLE—There is good news and bad news to report for pregnant women with epilepsy and their offspring, said William Cahill, MD, and colleagues. On the positive side, newborns of pregnant women on antiepileptic drug therapy showed no significant effects regarding gestational age at birth, birth weight, or the prevalence of those who were small for gestational age. In addition, the researchers found no significant difference in the occurrence of neonatal compromise as measured by the five-minute Apgar score between infants of mothers on antiepileptic drug therapy and those of mothers whose epilepsy did not require medication.

On the downside, however, Dr. Cahill’s team found that mothers with epilepsy who were taking antiepileptic drugs were more likely to have seizures in the first trimester and that mothers on polytherapy were more likely to require dosage adjustment of their antiepileptic medications and hospitalization for seizures.

“These findings support close monitoring of the clinical course of women with epilepsy during pregnancy,” advised Dr. Cahill. “This study also points out the clinical significance of epilepsy in pregnancy.” Dr. Cahill is an Assistant Professor of Neurology at the University of Cincinnati. He presented his findings at the 2002 Annual Meeting of the American Epilepsy Society.

Epilepsy affects from .6% to 1% of the population, many of whom are women of childbearing age. Increased fetal risks with the use of antiepileptic drugs in pregnancy include major congenital malformations, minor anomalies, neonatal hemorrhage, and possible adverse neurodevelopmental outcome, which need to be balanced with the risks to the mother and fetus from the epilepsy, said Dr. Cahill. Often, he added, epilepsy cannot be left untreated because of the risks to the mother and to the unborn child.

Women are affected by a number of physiologic changes during pregnancy. Plasma volume increases 50% by the third trimester, hepatic clearance increases, serum albumin concentrations decrease, and protein binding changes. “These changes may alter drug metabolism, but the amount and timing of these changes is unclear,” he said. “Very little is known about antiepileptic drug dosing requirements during pregnancy, further complicating epilepsy management in pregnant women.”

Several studies have examined antiepileptic drug use in pregnancy but have been limited by their size, polypharmacy, and dosing adjustments. Although a higher incidence of adverse fetal outcomes has been reported in pregnancies of mothers with epilepsy, other studies have minimized the impact of pregnancy on epilepsy control. Until the work of Dr. Cahill and colleagues, no recent, large studies had been conducted in the United States on mothers with epilepsy.

The University of Cincinnati Medical Center established a clinical protocol in 1991 for the management of pregnant women with epilepsy, which included monthly visits and monitoring of antiepileptic drug levels. Compliance with visits varied among the women. From 1991 to 2001, 215 mothers with epilepsy for whom birth outcomes were available were evaluated.

Of these, 25 were not taking any antiepileptic drug, as per their preference as well as that of their treating physicians. Antiepileptic drug monotherapy was used to treat 129 (68%) of the patients; 61 (32%) women received antiepileptic drug polytherapy.

Dr. Cahill’s team evaluated such clinical features of the mothers as age and gravidity, changes in seizure control, the need for hospitalization due to seizure activity, and antiepileptic drug dosage. Pregnancy outcomes were reviewed and included factors such as birth weight, the proportion of infants who were small for gestational age, and five-minute Apgar scores.

Overall, the researchers found that newborns to women with epilepsy showed little effect from their mothers’ antiepileptic drug therapy. “There was no significant difference between the three groups regarding the gestational age, time of birth, birth weight, or the proportion of small-for-gestational-age infants,” said Dr. Cahill. In addition, he noted, the average infant was born at term.

As for the mothers, those who were not taking an antiepileptic drug were slightly younger than those in the two treatment groups, and the proportion of prima gravida mothers was higher in the untreated group. Little difference was noted in these variables between the two treated groups. Meanwhile, the investigators found that seizures occurred in the first trimester in 31% of all pregnancies. “This was significantly greater in the treated groups compared to the mothers without antiepileptic drug therapy,” observed Dr. Cahill. “One in eight pregnancies was complicated by hospitalization secondary to seizure, with a rate significantly higher in the treated groups.”

The dosage of antiepileptic drugs was adjusted in 43% of these pregnancies. In nearly two thirds of all cases, it was increased due to seizure activity. “The highest incidence of first trimester seizures, hospitalization for secondary seizures, and antiepileptic drug increase occurred in mothers with epilepsy on polytherapy,” reported Dr. Cahill.

NR

—Colby Stong

Suggested Reading
Tettenborn B, Genton P, Polson D. Epilepsy and women’s issues: an update. Epileptic Disord. 2002;4(suppl 2):23-32.

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