The U.S. Food and Drug Administration (FDA) has labeled Zonegran as "Pregnancy Category C" and recommends that women who could possibly become pregnant should use effective birth control while using Zonegran. Recognizing that seizures in the mother also may be hazardous to a fetus, however, they conclude that the risks and benefits must be weighed in considering the use of Zonegran during pregnancy.

The use of Zonegran by pregnant women hasn't been fully studied. A prospective study of pregnancy outcomes in Zonegran-treated women at member hospitals of the Japanese Epilepsy Society between 1989 and 1994 identified 26 offspring, including 4 children born to women on Zonegran monotherapy. Among the 22 offspring exposed to AED polytherapy, malformations occurred in two (anencephaly in one and atrial septal defect in the other). No malformations occurred in children exposed to Zonegran monotherapy. Because of the small sample size, these results should be interpreted with caution.

When Zonegran was given to pregnant mice, rats, and dogs early in pregnancy, there were high rates of fetal abnormalities, especially heart defects and skeletal malformations. After it was given to monkeys during certain stages of pregnancy, many of the fetuses died, possibly because of malformations. All of these effects occurred at doses (and blood levels in the mother) that were equivalent to the amounts used to treat epilepsy in humans, or sometimes even lower. There was also a higher rate of death among the offspring of rats who were given Zonegran late in their pregnancy.

Advise women who are capable of becoming pregnant to take at least 400 mcg (0.4 mg) of folic acid (folate) daily to help prevent neural tube defects. Women at high risk, such as those with a history of a neural tube defect in a previous pregnancy, should take 4000 mcg (4 mg) daily, beginning before they become pregnant.

About 20% to 35% of women have seizures more often during pregnancy because of changes in hormones or changes in how an AED is metabolized. Though specific effects of pregnancy on Zonegran are not known, serum levels should be checked regularly during pregnancy so that the dosage can be adjusted as needed.

It is not known whether Zonegran is found in human milk. The effect on labor and delivery also is unknown.

Studies in rats showed decreases in fertility when Zonegran was given. Its effect on human fertility is unknown.