Blood was taken at the first antenatal clinic from 56049 pregnant women. Neural tube defect (NTD) pregnancies (81) were compared to controls (247) for plasma vitamin B12(B12) (ng/l), plasma folate (μg/1), and red cell folate (RCF) (μg/l). Median values were significantly different and were, respectively, 243 and 296 (p=0.001); 3.47 and 4.59 (p=0.002); and 269 and 338 (p<0.001). There was a significant correlation between plasma B12and RCF in cases (r=0.31,p=0.004) but not in controls (r=0.02,p=0.725). In cases only, multiple regression showed that both plasma B12and plasma folate influenced the maternal RCF (multipler=0.68, p<0.001). Plasma folate and plasma B12wereindependentrisk factors for NTDs, suggesting that the enzyme methionine synthase is involved directly or indirectly in the aetiology. The levels of folate and B12where increased risk occurred were not those usually associated with deficiency, calling for a re-evaluation of their recommended daily allowances. Whether the aetiology is purely nutritional or a metabolic defect, this study suggests that consideration should be given to including B12as well as folic acid in any programme of supplementation or food fortification to prevent NTD
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