Best Evidence Summary of Folic Acid Supplementation for Prevention of Neural Tube Defects in Women of Childbearing Age

TL;DR

This study summarizes the best evidence on folic acid supplementation to prevent birth defects in women of childbearing age.

Contribution

The study provides a structured evidence summary to guide clinical practice in regions without mandatory folic acid food fortification.

Findings

Folic acid supplementation should start at least 3 months before conception and continue through the first trimester.

Daily doses vary by risk level: 0.4 mg for low-risk, 1.0 mg for moderate-risk, and 4.0–5.0 mg for high-risk women.

Dietary intake alone is insufficient, and routine folate testing is not recommended.

Abstract

Objectives: To summarize the best evidence regarding folic acid supplementation for preventing neural tube defects (NTDs) in women of childbearing age and to develop a structured evidence summary for guiding clinical practice. Methods: We systematically searched multiple databases and professional websites from 1 January 2013 to 18 September 2025. Sources included 7 databases and 20 professional websites. The search targeted clinical guidelines, expert consensuses, best practices, and recommended practices on folic acid supplementation for NTD prevention in women of childbearing age. The retrieved literature underwent quality assessment, evidence extraction, and summarization. Results: The review included 17 publications: 10 guidelines, 4 expert consensuses, 2 recommended practices, and 1 best practice. From these, 14 distinct evidence statements were synthesized and organized into five thematic dimensions: risks of neural tube defects and the role of folic acid, time window of neural tube closure, timing and dosage of folic acid supplementation, relationship between dietary folic acid and folic acid tablets, and folic acid-related testing. The key recommendations include initiating supplementation at least 3 months preconception, with daily doses of 0.4 mg for low-risk, 1.0 mg for moderate-risk, and 4.0–5.0 mg for high-risk women, continuing through the first trimester, emphasizing that dietary intake alone is insufficient, and advising against routine folate testing. Conclusions: This study synthesized the best available evidence regarding folic acid supplementation for preventing NTDs in women of childbearing age, providing an evidence-based foundation to inform clinical practice, particularly for healthcare systems and populations in regions without mandatory folic acid food fortification.

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