title: Vitamin B-12 and neural tube defects: the Canadian experience.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, Banting Institute, University of Toronto, Toronto, ON, Canada.
authors.forename: Miles D
authors.initials: MD
authors.lastname: Thompson
authors.forename: David E C
authors.initials: DE
authors.lastname: Cole
authors.forename: Joel G
authors.initials: JG
authors.lastname: Ray
mesh_terms: D000328:Adult; D001682:Biological Availability; D015415:Biomarkers / Q000097:blood; D002170:Canada; D005260:Female; D005433:Flour; D005492:Folic Acid / Q000008:administration & dosage; D005527:Food, Fortified; D006801:Humans; D008764:Methylmalonic Acid / Q000097:blood; D009436:Neural Tube Defects / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D009752:Nutritional Status; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic; D014155:Transcobalamins; D014805:Vitamin B 12 / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D014806:Vitamin B 12 Deficiency / Q000150:complications / Q000453:epidemiology*; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000097:blood
chemical_list: D015415:Biomarkers; D014155:Transcobalamins; D014803:Vitamin B Complex; D008764:Methylmalonic Acid; D005492:Folic Acid; D014805:Vitamin B 12