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Q J Med 1993; 86: 703-708
© 1993 Association of Physicians

research-article

Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects

P. N. KIRKE1,2, A. M. MOLLOY3, L. E. DALY2, H. BURKE1, D. C. WEIR3 and J. M. SCOTT4,

1From the Health Research Board Dublin 2Department of Public Health Medicine and Epidemiology, University College Dublin 3Department of Clinical Medicine, Trinity College Dublin 4Department of Biochemistry, Trinity College Dublin

Address correspondence to Professor John M. Scott, Dept, of Biochemistry, Trinity College Dublin, Dublin 2, Ireland.

Received 26 July 1993 Accepted for publication 8 September 1993.

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 B12 and 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 B12 and plasma folate influenced the maternal RCF (multiple r = 0.68, p < 0.001). Plasma folate and plasma B12 were independent risk factors for NTDs, suggesting that the enzyme methionine synthase is involved directly or indirectly in the aetiology. The levels of folate and B12 where 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 B12 as well as folic acid in any programme of supplementation or food fortification to prevent NTDs.


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