Blood folic acid and vitamin B12 in relation to neural tube defects

Br J Obstet Gynaecol. 1996 Apr;103(4):319-24. doi: 10.1111/j.1471-0528.1996.tb09735.x.


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 all studies.

Design: Stored blood samples collected as part of a randomised trial of vitamin supplementation in the prevention of neural tube defects were retrieved from affected pregnancies (cases) and unaffected pregnancies (controls). Four controls were matched with each case by centre, maternal age and duration 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 combined with those already published from other studies to obtain an overall 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-seven 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 studies from the literature showed that on average, during the 1st trimester of pregnancy, serum folic acid was 0.6 ng/ml lower in neural tube defect 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 logistic regression showed no association between serum B12 and neural tube defects after allowing for serum folic acid.

Conclusion: our results are consistent with other evidence that folic acid and vitamin B12 levels are lower in women with neural tube defect pregnancies and consistent with evidence from randomised trials which showed that folic acid is protective.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Review
  • Systematic Review

MeSH terms

  • Female
  • Folic Acid / blood*
  • Humans
  • Neural Tube Defects / blood*
  • Pregnancy / blood*
  • Risk Factors
  • Vitamin B 12 / blood*


  • Folic Acid
  • Vitamin B 12