Physiologic changes in homocysteine metabolism in pregnancy: a longitudinal study in Spain

Nutrition. 2011 Sep;27(9):925-30. doi: 10.1016/j.nut.2010.10.017. Epub 2011 Mar 2.


Objective: The aim was to investigate whether pregnancy-induced changes in total homocysteine (tHcy) are associated with folate and vitamin B12 nutritional status, genetic C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) enzyme, and gestation outcome at a time when folic acid supplementation started to be recommended in the Spanish health system.

Methods: In total 154 pregnant women were recruited from among gynecologic patients of the Alcorcón Public Hospital Outpatient Clinic (Madrid, Spain). Blood tests were performed at weeks 15, 24, and 32 of pregnancy. Total Hcy, folate, and vitamin B12 serum fasting concentrations were measured using an IMx system. Genotype analyses were done by polymerase chain reaction/restriction fragment/length polymorphism analysis.

Results: Folate and vitamin B12 serum concentrations decreased significantly (P < 0.01) through pregnancy and reached the lowest values in the third trimester. Serum tHcy concentrations were significantly (P < 0.01) lower in the second trimester but increased in the third trimester. Frequencies of MTHFR C667T genotype were CC (35.7%), CT (57.2%), and TT (7.1%). Total Hcy concentration was not statistically influenced by maternal genotype. Plasma folate was the single negative predictor of maternal tHcy in the first trimester of pregnancy; 11.1% of gestations resulted in intrauterine growth restriction, 7.9% in gestational diabetes mellitus, and 4.8% in gestational hypertension. No significant differences in serum folate, vitamin B12, or tHcy concentrations were found in complicated pregnancies and these were unrelated to MTHFR genotype.

Conclusion: Although tHcy seems to be physiologically low in this Spanish population and unrelated to folate and B12 nutritional status, C677T MTHFR genotype, and some pregnancy complications, we support the statement that appropriate folate concentration may be important throughout pregnancy to prevent abnormalities associated with altered status (e.g., neural tube defects). According to our study, supplementation with folic acid seems to achieve this purpose because diet alone may be insufficient. In addition, a poor vitamin B12 status, as measured by plasma levels, may indicate that supplementation of both vitamins is needed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diabetes, Gestational / blood
  • Diabetes, Gestational / genetics
  • Dietary Supplements
  • Female
  • Fetal Growth Retardation / blood
  • Fetal Growth Retardation / genetics
  • Folic Acid / administration & dosage
  • Folic Acid / blood*
  • Genotype
  • Homocysteine / blood*
  • Humans
  • Hypertension, Pregnancy-Induced / blood
  • Hypertension, Pregnancy-Induced / genetics
  • Longitudinal Studies
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Nutrition Policy
  • Polymorphism, Genetic*
  • Pregnancy / blood*
  • Pregnancy / genetics
  • Pregnancy Complications / blood*
  • Pregnancy Complications / genetics
  • Prevalence
  • Spain / epidemiology
  • Vitamin B 12 / blood*


  • Homocysteine
  • Folic Acid
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Vitamin B 12