Increased risk of cancer in children born to mothers with epilepsy using high-dose folic acid during pregnancy (Folic acid, not bio-available folate forms like Metafolin).

Medical Xpress / University of Bergen / JAMA Neurology ^ | Sept. 28, 2022 | Håkon Magne Vegrim et al

[ConservativeMind]

High-dose folic acid is protective against congenital malformations if the mother is at particular risk of having a child with congenital malformations. Treatment with antiseizure medication in pregnancy is associated with risk of congenital malformations in the children, and women with epilepsy are therefore often recommended a supplementary high dose of folic acid (4–5 mg daily) before and during pregnancy. However, some studies have raised concern that folic acid can increase the risk of cancer not only in the mother, but in the child when exposed during pregnancy.

"We found an increased risk of childhood cancer if the child was born to a mother with epilepsy who filled for high dose folic acid before or during pregnancy, compared to children born to mothers with epilepsy without such prescription fills. The increased risk of cancer did not change after considering other factors that could explain the risk, such as concomitant fill for antiseizure medication. We did not find an increased cancer risk among children of mothers without epilepsy who used high-dose folic acid," says Håkon Magne Vegrim, MD and Ph.D. student.

The findings could not be explained by maternal epilepsy or other comorbidities such as diabetes mellitus, previous cancer diagnosis or specific antiseizure medications such as valproate or carbamazepine. Although these are unique and concerning results that have potential to change clinical practice worldwide, it should be interpreted with caution:

"The benefit of folic acid supplements for child neurodevelopment in pregnant women using antiseizure drugs has been shown in several studies," says Marte Helene Bjørk. "Folate is important for normal growth and brain development of the unborn child. Whereas the current study raise concern about the safety of high-dose folic acid supplementation, no risk of cancer has been found in children after maternal low dose folic acid (0.4 mg) in pregnancy."

[ConservativeMind]

Folic acid is a form of folate that floats around in our bodies for weeks or more. It gets converted to what we ostensibly need when we need it, but the high circulating levels have previously been found to be a problem with a few other health issues.

The Upper Tolerable Limit for folate/folic acid is 1,000 mcg (not mg). I have seen studies suggesting going over 400 mcg total a day can cause some people issues, though.

Note that low dose folic acid did not cause a cancer problem and that high dose folic acid only caused a cancer issue with epileptics.

Two active folate forms are Metafolin (L-[6S]-5-methyltetrahydrofolate) and Quatrefolic.

[ConservativeMind]

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Only for moms with epilepsy? Or avoiding high doses of folate for all moms a good idea?

[ConservativeMind]

The way I read it is that some medicines, such as anti-epileptic drugs, interfere with folic acid conversion into active folate.

This makes it seem hazardous to have the folic acid form of folate in such high amounts, in a situation in which it can't either be converted or utilized as active folate, instead, left floating around in the bodies of the mother and fetus, potentially for months.

It again drives home that the folic acid form of folate has “issues.”