Beyond Folate: The Emerging Role of Maternal Vitamin B12 in Neural Tube Development

source extracted confidence: high 2026-04-09
#female #humans #pregnancy #dietary-supplements #folic-acid

Beyond Folate: The Emerging Role of Maternal Vitamin B12 in Neural Tube Development

Nie et al., 2025 | Nutrients | Meta Analysis

Citation

Nie Lirong, Liu Xinru, ... Liu Jufen. Beyond Folate: The Emerging Role of Maternal Vitamin B12 in Neural Tube Development. Nutrients. 2025-Jun-19;17(12). doi:10.3390/nu17122040

Abstract

Background/Objectives: Folic acid (FA) supplementation can effectively reduce the occurrence of neural tube defects (NTDs). Vitamin B12 is involved in folate metabolism; however, studies have not reached a definitive conclusion on the association between vitamin B12 and NTDs independent of folate levels. A systematic review and meta-analysis were performed to summarize existing research and investigate the effect of vitamin B12 on NTDs. Methods: Studies were systematically searched in PubMed, Web of Science, Embase, and Cochrane, published before 1 March 2024. Standardized mean difference (SMD) with 95% confidence interval (CI) was employed to assess the association between maternal vitamin B12 in blood and NTDs. Results: A total of 38 studies were included, with a total of 2316 NTDs and 4298 controls, covering 14 countries worldwide. Compared with the non-NTD group, the NTD group exhibited a lower vitamin B12 level [SMD = -0.23, 95% CI (-0.32, -0.14), p < 0.001, I2 = 58.3%] with a statistically significant difference. Additionally, there was a significant association between maternal vitamin B12 concentration and NTDs when there was no significant difference in folate between the NTD and control groups [SMD: -0.19, 95% CI (-0.28, -0.10)]. Conclusions: Vitamin B12 supplement is also essential for the prevention of NTDs besides folic acid. Monitoring vitamin B12 concentration among pregnant women and considering appropriate supplementation with a combination of vitamin B12 and folic acid could be explored.

Key Findings

A total of 38 studies were included, with a total of 2316 NTDs and 4298 controls, covering 14 countries worldwide. Compared with the non-NTD group, the NTD group exhibited a lower vitamin B12 level [SMD = -0.23, 95% CI (-0.32, -0.14), p < 0.001, I2 = 58.3%] with a statistically significant difference. Additionally, there was a significant association between maternal vitamin B12 concentration and NTDs when there was no significant difference in folate between the NTD and control groups [SMD: -0.

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population pregnant women
Sample Size 38
Age Range See abstract
Condition See abstract

MeSH Terms

  • Female
  • Humans
  • Pregnancy
  • Dietary Supplements
  • Folic Acid
  • Maternal Nutritional Physiological Phenomena
  • Neural Tube
  • Neural Tube Defects
  • Vitamin B 12
  • Vitamin B 12 Deficiency

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis, Systematic Review
  • Vertical: folate-pregnancy

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09