Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic Acid fortification

Pediatrics. 2009 Mar;123(3):917-23. doi: 10.1542/peds.2008-1173.


Objective: Folic acid fortification has reduced neural tube defect prevalence by 50% to 70%. It is unlikely that fortification levels will be increased to reduce neural tube defect prevalence further. Therefore, it is important to identify other modifiable risk factors. Vitamin B(12) is metabolically related to folate; moreover, previous studies have found low B(12) status in mothers of children affected by neural tube defect. Our objective was to quantify the effect of low B(12) status on neural tube defect risk in a high-prevalence, unfortified population.

Methods: We assessed pregnancy vitamin B(12) status concentrations in blood samples taken at an average of 15 weeks' gestation from 3 independent nested case-control groups of Irish women within population-based cohorts, at a time when vitamin supplementation or food fortification was rare. Group 1 blood samples were from 95 women during a neural tube defect-affected pregnancy and 265 control subjects. Group 2 included blood samples from 107 women who had a previous neural tube defect birth but whose current pregnancy was not affected and 414 control subjects. Group 3 samples were from 76 women during an affected pregnancy and 222 control subjects.

Results: Mothers of children affected by neural tube defect had significantly lower B(12) status. In all 3 groups those in the lowest B(12) quartiles, compared with the highest, had between two and threefold higher adjusted odds ratios for being the mother of a child affected by neural tube defect. Pregnancy blood B(12) concentrations of <250 ng/L were associated with the highest risks.

Conclusions: Deficient or inadequate maternal vitamin B(12) status is associated with a significantly increased risk for neural tube defects. We suggest that women have vitamin B(12) levels of >300 ng/L (221 pmol/L) before becoming pregnant. Improving B(12) status beyond this level may afford a further reduction in risk, but this is uncertain.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Case-Control Studies
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Folic Acid / administration & dosage*
  • Humans
  • Infant, Newborn
  • Ireland
  • Neural Tube Defects / blood
  • Neural Tube Defects / epidemiology*
  • Neural Tube Defects / prevention & control
  • Pregnancy
  • Pregnancy Complications / blood
  • Pregnancy Complications / drug therapy
  • Pregnancy Complications / epidemiology*
  • Pregnancy Trimester, Second
  • Prenatal Care
  • Risk
  • Secondary Prevention
  • Vitamin B 12 / blood
  • Vitamin B 12 Deficiency / blood
  • Vitamin B 12 Deficiency / drug therapy
  • Vitamin B 12 Deficiency / epidemiology*
  • Young Adult


  • Folic Acid
  • Vitamin B 12