Low maternal vitamin B(12) is a risk factor for neural tube defects: a meta-analysis

J Matern Fetal Neonatal Med. 2012 Apr;25(4):389-94. doi: 10.3109/14767058.2011.580800. Epub 2011 Jun 1.


Objective: The objective of this study was to assess whether low level of maternal vitamin B(12) is associated with an increased risk of fetal neural tube defects (NTDs), in order to contribute to research on further reduction of NTDs under a background of mandatory folic acid (FA) fortification.

Methods: A meta-analysis was conducted. We retrieved and evaluated the studies published on the risk of low level of maternal vitamin B(12) for NTDs. The homogeneity of the studies was examined using the forest graph. Meta-analysis was applied to calculate the odds ratio (OR) of fetal NTDs in relation to low maternal B(12) and its 95% confidence interval (CI).

Results: We identified nine published articles including 567 cases and 1566 controls in the meta-analysis. All the studies selected were homogeneous according to the forest graph (χ(2) = 15.05, P < 0.1). The estimated OR value of fetal NTDs in relation to low maternal B(12) was 2.41 (95% CI: 1.90-3.06).

Conclusion: Low maternal B(12) status could be an important risk factor for the development of fetal NTDs. The addition of synthetic B(12) to current recommendations for periconceptional FA tablet supplements or FA-fortified foods should be considered.

Publication types

  • Meta-Analysis

MeSH terms

  • Female
  • Geography
  • Humans
  • Infant, Newborn
  • Maternal Nutritional Physiological Phenomena
  • Maternal-Fetal Exchange / physiology
  • Neural Tube Defects / epidemiology*
  • Neural Tube Defects / etiology*
  • Nutritional Status / physiology
  • Odds Ratio
  • Pregnancy
  • Risk Factors
  • Vitamin B 12 / blood
  • Vitamin B 12 Deficiency / blood
  • Vitamin B 12 Deficiency / complications*
  • Vitamin B 12 Deficiency / epidemiology*


  • Vitamin B 12