Neural tube defects result from the failure of the neural tube to close within the first four weeks of pregnancy. That leads to conditions such as spina bifida, anencephaly, and encephalocele. Since this closure process occurs very early—often before pregnancy is recognized—FA intake before conception is essential for effective prevention.

The World Health Organization (WHO) recommends that pregnant women who are overweight or obese take 5 mg of FA per day, compared to the standard dose of 400 µg, due to their increased metabolic demand and lower plasma folate levels.

One of the most concerning findings from the review is the low adherence to FA supplementation recommendations among obese women. Only 4–9.5% of them take the recommended 5 mg daily dose, and in most cases, supplementation begins after conception, when the critical window for prevention has already closed. This underscores the need for increased awareness about the importance of FA supplementation, especially among women with a high body mass index (BMI).

Women with overweight or obesity tend to have lower plasma folate levels due to several factors:

• Chronic low-grade inflammation that alters folate metabolism.
• Increased metabolic demand due to excess body weight.
• Higher activity of the cytochrome P450 enzyme (CYP2E1), which utilizes FA as a substrate, reduces its availability.
• Poor dietary intake of folates, with lower consumption of leafy green vegetables, legumes, and fortified foods.

To reduce the risk of neural tube defects and improve adherence to guidelines, the review authors propose several strategies:

• Standardizing FA supplementation guidelines across all European countries.
• Regularly monitoring folate levels in women of childbearing age, particularly those with excess weight.
• Educational campaigns to raise awareness of folate deficiency consequences and the importance of preconceptional supplementation.
• Mandatory food fortification with FA has been implemented in several countries to ensure adequate intake.

The review by Loperfido et al. (2025) highlights an underestimated public health issue. Despite clear scientific evidence on the benefits of folic acid in preventing neural tube defects, adherence to supplementation recommendations remains inadequate, especially among women with a high BMI.

Longitudinal studies are needed to assess the impact of FA supplementation on NTD incidence and to develop personalized supplementation protocols. At the same time, public health policies should include targeted educational campaigns and food fortification strategies to reduce the risk of congenital malformations and ensure greater equity in nutritional access during pregnancy.