Homocysteine metabolism in pregnancies complicated by neural-tube defects

Lancet. 1995 Jan 21;345(8943):149-51. doi: 10.1016/s0140-6736(95)90165-5.


Folic acid taken around the time of conception can prevent many neural-tube defects. Women with low-normal vitamin B12 values may also be at increased risk. We considered whether homocysteine metabolism via the enzyme methionine synthase, which requires both folate and B12, could be the critical defect in folate-related neural tube defects. Blood was obtained during pregnancies that produced 81 infants with neural-tube defects and 323 normal children. Samples were assayed for homocysteine, methylmalonic acid, plasma folate, red-cell folate, and B12. Mothers of children with neural-tube defects had significantly higher homocysteine values (8.62 [SD 2.8] mumol/L) than did B12-matched controls (7.96 [2.5] mumol/L, p = 0.03). The difference was significant (p = 0.004) in the lower half of the B12 distribution after adjusting for plasma folate. Our study shows that an abnormality in homocysteine metabolism, apparently related to methionine synthase, is present in many women who give birth to children with neural-tube defects. Overcoming this abnormality is likely to be the mechanism by which folic acid prevents neural-tube defects. These findings suggest that the most effective periconceptional prophylaxis to prevent neural-tube defects may require B12 as well as folic acid.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / metabolism
  • Analysis of Variance
  • Female
  • Folic Acid / blood
  • Homocysteine / blood
  • Homocysteine / metabolism*
  • Humans
  • Infant, Newborn
  • Methylation
  • Methylmalonic Acid / blood
  • Neural Tube Defects / etiology*
  • Pregnancy / blood
  • Pregnancy / metabolism*
  • Vitamin B 12 / blood


  • Homocysteine
  • Methylmalonic Acid
  • Folic Acid
  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
  • Vitamin B 12