Low Vitamin B12 May Increase Risk for Neural Tube Defects

Molloy AM, Kirke PN, Troendle JF, et al. 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 1;123(3):917-919.

http://pediatrics.aappublications.org/cgi/content/abstract/123/3/917
http://pediatrics.aappublications.org/cgi/content/full/123/3/917
http://pediatrics.aappublications.org/cgi/reprint/123/3/917

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Published online March 2, 2009
PEDIATRICS Vol. 123 No. 3 March 2009, pp. 917-923 (doi:10.1542/peds.2008-1173)

ARTICLE
Maternal Vitamin B12 Status and Risk of Neural Tube Defects in a Population With High Neural Tube Defect Prevalence and No Folic Acid Fortification
Anne M. Molloy, PhDa, Peadar N. Kirke, FFPHMIb, James F. Troendle, PhDc, Helen Burke, BSocScb, Marie Sutton, MB, MPHb, Lawrence C. Brody, PhDd, John M. Scott, ScDe and James L. Mills, MD, MSc

a Schools of Medicine
e Immunology and Biochemistry and Immunology, Trinity College, Dublin, Ireland
b Child Health Epidemiology Unit, Health Research Board, Dublin, Ireland
c Division of Epidemiology, Statistics, and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
d Molecular Pathogenesis Section, Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland
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 B12 is metabolically related to folate; moreover, previous studies have found low B12 status in mothers of children affected by neural tube defect. Our objective was to quantify the effect of low B12 status on neural tube defect risk in a high-prevalence, unfortified population.
METHODS. We assessed pregnancy vitamin B12 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 B12 status. In all 3 groups those in the lowest B12 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 B12 concentrations of CONCLUSIONS. Deficient or inadequate maternal vitamin B12 status is associated with a significantly increased risk for neural tube defects. We suggest that women have vitamin B12 levels of >300 ng/L (221 pmol/L) before becoming pregnant. Improving B12 status beyond this level may afford a further reduction in risk, but this is uncertain.

Key Words: vitamin B12 • cobalamin • neural tube defects • folic acid fortification • folate

Abbreviations: NTD—neural tube defect • B12—vitamin B12 • AP—affected pregnancy • NAP—nonaffected pregnancy • RCF—red cell folate • OR—odds ratio

Accepted Jul 22, 2008.

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