The systematic review published in Reproductive Health suggests there is “scarce adherence” to folic acid guidelines, highlighting an “urgent need to standardize the recommendations across European countries.”
The researchers at the University of Pavia, ICS Maugeri and Haleon Italy S.R.L. recommend monitoring overweight women of childbearing age and assessing markers for folate and homocysteine metabolism to enable personalized supplementation.
“These improvements should be supported by educational policies involving cooperation among healthcare professionals, medical doctors, policymakers and citizens to enhance awareness among women of childbearing age about their pivotal role in supporting health across generations,” they wrote.
Obesity and neural tube defects
Research indicates that obese pregnant women are at significantly higher risk of neural tube defects such as spina bifida compared with women of normal weight.
The current study noted that women with obesity “may have a lower folate level caused by a state of chronic low-grade inflammation, which results in an increased metabolic requirement.”
Older evidence suggests that although obese individuals show lower serum folate levels, their red blood cell concentrations are higher. The current researchers noted that this “obesity paradox” may be due to increased activity of the cytochrome P450 (CYP) 2E1 enzyme, which uses folic acid as a substrate.
“For these vulnerable women, a higher dose of 5 mg of FA is recommended by the World Health Organization guidelines,” the researchers wrote.
Food fortification
The current systematic review included studies from European countries that adhered to a policy of voluntary folic acid fortification. The authors noted that mandatory fortification in the United States “has demonstrated a reduction in NTDs [neural tube defects] incidence by 25–30%, approximately 50% of the preventable fraction with folic acid.”
“This study further proves the urgent need for European countries to consider requiring the fortification of staple foods with folic acid,” Scott Montgomery, director of the Food Fortification Initiative, told Nutraingredients.
“Because the neural tube forms in the first weeks of pregnancy, often before a woman knows she is pregnant, relying on supplementation alone is not an effective way to prevent neural tube defects.”
“Folic acid fortification, practiced in more than 60 high-, middle- and low-income countries, is a proven, safe way to ensure all women get enough folate to help prevent birth defects,” he added.
Study details
Of 1,718 records identified, the systematic review included eight studies of overweight pregnant women who took folic acid.
In three studies, women took folic acid prior to conception, and the rest took the supplement starting from the first trimester.
The results revealed that between 4% and 9.5% of women with obesity adhered to folic acid recommendations. The researchers noted that 61% started the supplementation after conception, “highlighting that European pregnant women are not particularly adherent to recommendations during the period of greatest need.”
Source: Reprod Health, 22, 13. doi: 10.1186/s12978-025-01953-y. “Folic acid supplementation in European women of reproductive age and during pregnancy with excessive weight: a systematic review”. Authors: F. Loperfido et al.