However, lead author Hakon Vegrim, MD, a doctoral student at the University of Bergen, Norway, said the research at this point precludes recommending that women discontinue folic acid because of its proven ability to prevent birth defects.
“This discovery came as a surprise to us,” said Dr. Vegrim neurology today In meetings, in your poster presentation.
Of the 27,572 mothers with epilepsy in the Nordic Register – made up mainly of health records from Norway, Sweden and Denmark – 5,881 mothers took high doses of folic acid, which they defined as 1 gram to 5 grams, during pregnancy.
Eighteen of the babies born to this group of women developed cancer, an incidence of 42.9 cases per 100,000 individuals and a rate 2.5 times higher than that seen in other groups of women. Among women with epilepsy who did not take high-dose folic acid, the incidence rate of cancer in their children was 18.6 per 100,000. The cancer incidence rate was 21.5 per 100,000 for women who took high doses of folic acid but did not have epilepsy. Among women who did not take high-dose folic acid and who did not have epilepsy, the incidence rate of cancer in their children was 19.8 per 100,000.
While the study data doesn’t indicate how many women were taking 1 gram a day or 5 grams a day, Dr. Vegrim said surveys indicated that most doctors recommend 5 grams a day.
“There are so many doses given in a prescription — often enough to cover an entire pregnancy — that we have no real idea if there’s a point where folic acid dosing becomes an issue,” he said.
In the study, Dr. Vegrim and his colleagues did not find that any particular type of childhood cancer posed a greater risk than others for the children of mothers with epilepsy.
“The proportion of cancers among children of women with epilepsy appears to be the same as the types of cancer seen in children of women who do not have epilepsy,” he said.
Commenting on the study, Kimford J. Meador, MD, FAAN, 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 replicated 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 1,000 live births. This incidence is higher than than the incidence of childhood cancer found in the Nordic study. In addition, periconceptional folic acid can reduce neural tube defects by more than 70 percent, reduce congenital heart defects by approximately 20 percent, and can improve cognitive outcomes in the population in general.”
“Although folic acid has not been shown to reduce malformations induced by anticonvulsant drugs, several studies have shown that it can improve cognitive and behavioral outcomes in exposed children. in utero to anticonvulsant drugs,” he added.
The Doctor. Meador noted that the 1 mg and 5 mg doses were grouped together as high-dose folic acid, so “we cannot examine whether there is a cutoff 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 unclear, 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 those risks are not clear,” he said. It’s important for cell growth.”
Dr. Meador said the study indicates that more research is needed in the area, but the findings do not warrant changes in practice at this time.
This work was supported by the NordForsk Nordic Program on Health and Welfare (Project #83796). The Doctor. Vegrim has not made any industry-related disclosures.
Link for more information:
AES Abstract 2.13: Vegrim H, Dreier JW, Alvesad S, et al. Maternal epilepsy, prenatal exposure to high doses of folic acid, and risk of childhood cancer: a Nordic registry-based cohort study.