BLOOD FOLIC-ACID AND VITAMIN-B12 IN RELATION TO NEURAL-TUBE DEFECTS

Objective To determine the relation between blood folic acid and serum vitamin B12 in neural tube defect pregnancies using data from the MRC Vitamin Study and a literature review of al studies. Design Stored bl ood samples collected as part of a randomised trial of vitamin supplem entation in the prevention of neural tube defects were retrieved from affected pregnancies (cases) and unaffected pregnancies (controls). Fo ur controls were matched with each case by centre, maternal age and du ration of storage of the blood sample. The samples had been collected from women at entry to the trial, immediately before the women became pregnant, and at around 12 weeks of pregnancy. Our results were combin ed with those already published from other studies to obtain an overal l assessment of blood folic acid and vitamin B12 in relation to neural tube defects. Setting Blood samples were collected as part of the MRC Vitamin Study. The collaborating centres were in the United Kingdom, Hungary, Israel, Australia, Canada and Russia. Participants Twenty-sev en women with neural tube defect pregnancies and 108 matched controls with unaffected pregnancies. Results Serum and red cell folic acid and serum vitamin B12 levels were lower in the cases than in controls at each of the three occasions when blood samples were collected, but no comparison was significant (P > 0.05). A systematic review of all stud ies from the literature showed that on average, during the Ist trimest er of pregnancy, serum folic acid was 0.6 ng/ml lower in neural tube d efect pregnancies (P < 0.01), red cell folic acid was 77 ng/ml lower ( P < 0.001) and serum vitamin B12 was 38 ng/l lower (P < 0.001). A logi stic regression showed no association between serum B12 and neural tub e defects after allowing for serum folic acid. Conclusion Our results are consistent with other evidence that folic acid and vitamin B12 lev els are lower in women with neural tube defect pregnancies and consist ent with evidence from randomised trials which showed that folic acid is protective.