Maternal Vitamin B12 Status and Risk of Neural Tube Defects in a Population With High Neural Tube Defect Prevalence and No Folic Acid Fortification

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. Pediatrics 2009;123: 917-923