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. 2025 Jan 31;22(1):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

Federica Loperfido #  1 , Francesca Sottotetti #  2 , Irene Bianco  2 , Dana El Masri  2 , Beatrice Maccarini  2 , Chiara Ferrara  2 , Antonio Limitone  3 , Hellas Cena #  2   4 , Rachele De Giuseppe #  2
Affiliations

Folic acid supplementation in European women of reproductive age and during pregnancy with excessive weight: a systematic review

Federica Loperfido et al. Reprod Health. .

Abstract

Objective: Neural tube defects (NTDs), well-known consequences of folate deficiency, are the second most common cause of serious birth defects, affecting approximately one in a thousand pregnancies in Europe. Maternal folate deficiency before conception and during early pregnancy has been suggested as the most important preventable risk factor for NTDs; thus women should be supplemented before conception with 0.4 mg of folic acid (FA) until the first trimester of gestation. Findings have described a positive association between elevated Body Mass Index (BMI) and birth defect risk; data on plasma folate levels in pregnant women with obesity have shown values lower than recommended because of a state of chronic low-grade inflammation, resulting in increased metabolic demands. Nowadays, disparities exist regarding the recommended dose of FA in women at risk, including women of childbearing age with excessive weight. Therefore, this systematic review aimed to investigate if European childbearing age/pregnant women with overweight/obesity are supplemented according to the current country-specific FA recommendations and whether the dosage of 5 mg recommended for pregnant women with obesity is effective in preventing NTDs.

Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. An electronic database search of manuscripts was carried out in Web of Sciences, PubMed and Medline. The quality of the included studies was assessed by using the Quality Assessment for Diverse Studies statement.

Results: Out of 1718 records identified, 8 manuscripts met all the inclusion criteria. Overall, the results showed that pregnant women with obesity adherent to FA recommendations ranged between 4% and 9.5%. Furthermore, the majority (61%) started the supplementation after conception, highlighting that European pregnant women are not particularly adherent to recommendations during the period of greatest need.

Conclusions: The scarce adherence to the current guidelines shows an urgent need to standardize the recommendations across European countries. Particularly, women of childbearing age with excess weight should be monitored assessing serum folate, RBC folate, and homocysteine levels developing tailored supplementation protocols, to counteract the occurrence of NTDs.

Keywords: Childbearing age; Folic acid; Neural tube defects; Pregnancy; Supplementation; Women with excessive weight.

Plain language summary

Neural tube defects (NTDs) are severe congenital abnormalities connected to maternal folate deficiency. Current international guidelines recommend a daily supplementation of 0.4 mg of folic acid (FA) starting before conception and during the first trimester of pregnancy, to prevent NTDs. Women with excessive weight need higher folic acid doses due to their altered metabolic demands. Women with obesity encounter a greater risk of NTDs, as they often have lower plasma folate levels. This deficiency may result from chronic low-grade inflammation and increased nutrient requirements. For these vulnerable women, a higher dose of 5 mg of FA is recommended by the World Health Organization guidelines. However, only 4–9.5% of pregnant women with obesity adhere to FA supplementation recommendations, taking FA supplementation after conception, and missing the critical preconception period necessary for effective NTDs prevention. There is an urgent need to standardize FA supplementation recommendations across European countries and to monitor the folate status of women with excess weight. This will help develop personalized supplementation strategies aimed at effectively reducing the risk of NTDs.

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Conflict of interest statement

Declarations. Competing interest: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of the study selection process, based on the PRISMA guidelines
See this image and copyright information in PMC

References

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