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EEC 2022 | Update: high-dose folic acid and antiseizure medications in pregnancy

Folate is critical for fetal growth and neurodevelopment and thus, supplementation is recommended for all women in the lead up to conception and in the early stages of pregnancy to help prevent birth defects. Women with epilepsy who are receiving treatment with antiseizure medications (ASMs) are often prescribed high-dose folic acid supplementation during pregnancy, due to the impacts of ASMs on its uptake and metabolism. Specific dosing is controversial, with little evidence to prove the safety and efficacy of high-dose folic acid in this setting. Marte-Helene Bjork, MD, PhD, Haukeland University Hospital, Bergen, Norway, outlines current data on the risks and benefits of folic acid supplementation in women taking ASMs who are pregnant or planning pregnancy. Findings from several studies support the importance of folic acid for neurodevelopment, with supplementation at the beginning of pregnancy shown to reduce the risk of autism spectrum disorder symptoms and impaired language development symptoms in the offspring. On the other hand, some data suggests no benefit of high dose supplementation regarding prevention of major malformations and has indicated an increased risk of childhood cancer. This interview took place at the 14th European Epilepsy Congress (EEC) 2022 in Geneva, Switzerland.

Transcript (edited for clarity)

The majority of neurologists will give women with epilepsy that are using antiseizure medications, high dose folic acid during pregnancy. There are no guidelines that give specific instructions on the right dose to use, but most neurologists will use five milligrams before conception and some use it during the first trimester and some throughout the pregnancy. However, this way of doing it is controversial because we don’t really have evidence that high dose folic acid is beneficial, or that this is safe...

The majority of neurologists will give women with epilepsy that are using antiseizure medications, high dose folic acid during pregnancy. There are no guidelines that give specific instructions on the right dose to use, but most neurologists will use five milligrams before conception and some use it during the first trimester and some throughout the pregnancy. However, this way of doing it is controversial because we don’t really have evidence that high dose folic acid is beneficial, or that this is safe. So my talk will concern what evidence we do have and what evidence we do have about risks.

Generally, during pregnancy, you need more folate than usual because the fetus is developing and since the cells are dividing, you need more folate to ensure that the cell can divide. So that’s why all women should take small dose of folic acid before conception and during the first trimester, to prevent spina bifida and other congenital malformations.

But for women with epilepsy, they probably need more folate because the antiseizure medications can interact with the folate. And so that the level of all is reduced and possibly also, the uptake in the placenta can be… Well, antiseizure medications can interfere with that process. So, that’s why probably women with epilepsy need folate more than others. And probably also in a higher dose. We have some evidence from previous research that women with epilepsy using antiseizure medication, that used any sort of folic acid supplements at the beginning of pregnancy, their child had reduced risk of having autistic spectrum disorder symptoms and also symptoms of impaired language development.

So in our data, it seems that if you are able to start with folic acid supplements early in pregnancy, that will be beneficial for the neurodevelopment of the fetus. Similarly, the NEAD study showed that women that used folic acid supplements, their children had higher IQ score than women that did not use folic acid supplements. So that also speaks for the benefit for neurodevelopment of the child.

However, when others studies have looked at supplement for prevention of major malformations in children exposed to antiseizure medications prenatally, they didn’t find any benefit. And also, there were some indications of an increased risk, that could be attributed to sort of biased by indication that those women using most antiseizure medication, used the most folic acid supplement, but you can’t really know for sure. So that’s why the data is not… It’s conflicting concerning what outcome you’re using. Also, lately we have some data that is under review for publication, showing that high dose folic acid supplements in women with epilepsy is associated with increased risk of childhood cancer in their child. So that’s some evidence for increased risk of high dosages.

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