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Vitamin B-12 and neural tube defects: the Canadian experience

¹ From the Department of Laboratory Medicine and Pathobiology, Banting Institute, University of Toronto, Toronto, ON, Canada (MDT and DECC), and the Departments of Medicine, Obstetrics and Gynecology, and Health Policy Management and Evaluation, St Michael's Hospital, University of Toronto, Toronto, Canada (JGR).

² Presented at the symposium "Is It Time for Mandatory Vitamin B-12 Fortification in Flour?" held at Experimental Biology 2008, San Diego, CA, 8 April 2008.

³ Supported by the Spina Bifida and Hydrocephalus Associations of Canada (JGR), the Physicians’ Services Incorporated (PSI) Foundation (JGR and DECC), and the Canadian Institutes for Health Research New Investigator Award (JGR) and postdoctoral fellowship (MDT).

⁴ Reprints not available. Address correspondence to DEC Cole, Room 415, Department of Laboratory Medicine and Pathobiology, Banting Institute, University of Toronto, 100 College Street, Toronto, ON, Canada, M5G 1L5. E-mail: davidec.cole{at}utoronto.ca.

Although early epidemiologic studies showed a protective effect of adequate maternal folic acid (FA) status against neural tube defects (NTDs), the role of adequate vitamin B-12 nutrition in the putative reduction of NTD frequency has remained uncertain. Evaluating vitamin B-12 status was complicated by the need to control for altered FA status after fortification in Canada. More recent studies have made use of better biomarkers of vitamin B-12 status, including methylmalonic acid and holotranscobalamin (holoTC). HoloTC provides a useful measure of vitamin B-12 status because it represents the bioavailable fraction of circulating vitamin B-12. By assessing bioavailable vitamin B-12 status in a large Canadian cohort accrued before and after FA fortification, we found a 3-fold increase in the risk of NTDs in mothers who had vitamin B-12 status in the lower quartile, regardless of FA fortification. Our work suggests that vitamin B-12 fortification, analogous to the FA fortification program, may reduce NTDs more than FA fortification alone. A multicenter randomized controlled trial comparing periconceptional vitamin B-12 in combination with FA against FA alone is warranted.

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