Are higher doses of folic acid in pregnancy safe?

MINNEAPOLIS, March 4, 2025 /PRNewswire/ -- Taking a higher dose of folic acid during the first trimester of pregnancy was safe and associated with improved verbal abilities in children at age six as well as improved behavior skills, according to a preliminary study released March 4, 2025, that will be presented at the American Academy of Neurology's 77^th Annual Meeting taking place April 5–9, 2025, in San Diego and online.

"Folic acid during pregnancy has been shown to reduce deformities and improve intellectual abilities in children, but the best dose of folic acid is unknown," said study author Kimford J. Meador, MD, PhD, of Stanford University in Palo Alto, California, and a Fellow of the American Academy of Neurology. "Our study provides new information showing a positive connection between taking folic acid during early pregnancy and brain health outcomes in children, with no evidence of negative effects at higher doses."

The study looked at 345 children when they were six years old. Of the participants, 262 were children of women with epilepsy and 83 were children of women without epilepsy.

Researchers recorded doses of folic acid taken by their mothers during the first 12 weeks of pregnancy and divided the children into five groups based on average dosage: no folic acid, folic acid up to 0.4 milligrams (mg) per day; more than 0.4 to 1.0 mg per day; more than 1.0 to 4.0 mg per day; and more than 4.0 mg per day. The current recommended dose during pregnancy for the general population is 0.4 mg per day, while women with epilepsy may be prescribed a higher dose.

Children were given multiple tests to assess verbal skills. For example, for one vocabulary test, participants were asked to describe objects, actions or concepts presented in each picture using one word. For the general population, scores for these verbal tests range from 70 to 130, with a mean of 100, with higher scores indicating better abilities.

Parents also completed questionnaires to assess the children's behaviors like communication skills, social skills and daily living skills. Results from these tests were combined for an overall standardized behavioral score. For the general population, scores range from 70 to 130, with a mean of 100, with higher scores indicating better abilities.

After adjusting for factors such as mother's IQ, epilepsy medications, and pregnancy complications, researchers found the average verbal score for children of women who took folic acid was 108 compared to 96 for children of women who did not take folic acid. The average behavioral score for children of women who took folic acid was 102 compared to 82 for children of women who did not take folic acid.

When looking only at children whose mothers took folic acid during pregnancy, researchers found scores were similar across low to high doses of folic acid. Children of mothers who took a low dose had a similar average verbal score of 110 compared to 108 for children of mothers who took a high dose. Children of those who took a low dose and children of those who took a high dose both had average behavioral scores of 103.

"While previous studies have found risks with higher doses, these findings are reassuring for people who are pregnant or planning to have children that taking a higher dose of folic acid early in pregnancy may still positively impact the brain health of their child," Meador said. "Additional studies are needed to determine the best dose of folic acid to maximize benefits and minimize risks to neurodevelopment as well as other outcomes, which could vary for different groups of women."

A limitation of the study was that it did not look at other factors that may affect folic acid intake and absorption, such as other vitamins taken and genetics.

The study was supported by the National Institute of Neurological Disorders and Stroke and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

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SOURCE American Academy of Neurology