Neurology Today

CHICAGO—Childhood cancer appears to be more common in children born to mothers with epilepsy who take high doses of folic acid during pregnancy to prevent devastating neural tube defects, researchers reported here at the American Epilepsy Society’s annual meeting.

However, lead author Hakon Vegrim, MD, a PhD student at the University of Bergen in Norway, said the study excludes the recommendation that women discontinue folic acid because of its proven ability to prevent birth defects.

“This finding was a surprise to us,” Dr. Vegrim to Neurology Today At the Meetings during his poster presentation.

Of the 27,572 mothers with epilepsy in the Nordic Registry – which consists mainly of health records from Norway, Sweden and Denmark – 5,881 mothers had taken a high dose of folic acid during pregnancy, which they defined as 1 gram to 5 grams.

Eighteen of the babies born to that group of women developed cancer, an incidence of 42.9 cases per 100,000 individuals and a frequency 2.5 times higher than other groups of women. Of the women with epilepsy who did not take a high dose of folic acid, the incidence of cancer in their children was 18.6 per 100,000. The cancer incidence was 21.5 per 100,000 for women who took high-dose folic acid but did not have epilepsy. Among women who did not take a high dose of folic acid and who did not have epilepsy, the incidence of cancer in their children was 19.8 per 100,000.

While the study data doesn’t indicate how many of the women took 1 gram per day or 5 grams per day, said Dr. Vegrim that studies have shown that most doctors recommend 5 grams per day.

“There are so many doses given in one prescription — usually enough to cover an entire pregnancy — that we have no idea if there’s a point where folic acid dosing becomes an issue,” he said.

In the study, Dr. Vegrim and colleagues did not think any particular childhood cancer had a greater risk than others for the children of mothers with epilepsy.

“The proportion of cancers among the children of women with epilepsy appears to be the same as the type of cancer seen in the children of women who do not have epilepsy,” he said.

Commenting on the study, Kimford J. Meador, MD, FAAN, a professor of neurology and neurological sciences at Stanford University School of Medicine in California, described the findings as “worrying but not definitive.”

“Several important issues should be noted,” said Dr. meador. “First, these findings need to be reproduced in a separate cohort. Second, the relative risks/benefits need to be considered. The incidence of neural tube defects in the general population is 1 to 5 per 1000 live births. This incidence is greater than the incidence for cancer found in children in the Scandinavian study. Furthermore, perconceptual folic acid can reduce neural tube defects by more than 70 percent, reduce congenital heart defects by about 20 percent, and may improve cognitive outcomes in the general population.”

“While folic acid has not been shown to reduce drug-induced malformations, several studies have shown that it can improve cognitive and behavioral outcomes in children exposed to anti-seizure drugs in utero,” he added.

dr. Meador noted that the 1 mg and 5 mg doses were pooled into a high dose of folic acid, so “we cannot investigate whether there is a cut-off point or dose-dependent effect on cancer risk. Many do not consider 1 mg per day to be a high dose. The optimal dose to produce positive effects is not clear even in the general population.”

Finally, said Dr. Meador, the mechanisms of positive or negative effects are unknown. “The genetic risks for neural tube defects and why folic acid reduces these risks is not clear,” he said. “The positive effects of folic acid come from supplements given early in pregnancy, but most women receive folic acid during pregnancy because folic acid is important for cell growth.”

dr. Meador said the study indicates more research is needed in the area, but the findings do not warrant a change in practice at this time.

This work was supported by the NordForsk Nordic Health and Wellness Program (project #83796). dr. Vegrim had no industry-related disclosures.

Link for more information:

AES Abstract 2.130: Vegrim H, Dreier JW, Alvestad S, et al. Maternal epilepsy, prenatal exposure to high-dose folic acid, and childhood cancer risk: a Scandinavian registry-based cohort study.

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