Distribution of 5-Methyltetrahydrofolate and Folic Acid Levels in Maternal and Cord Blood Serum: Longitudinal Evaluation of Japanese Pregnant Women

Nutrients. 2020 Jun 1;12(6):1633. doi: 10.3390/nu12061633.


"Total" folate in blood has usually been measured to evaluate the folate status of pregnant women. However, folate is composed of many metabolites. The main substrate is 5-methyltetrahydrofolate (5-MTHF), with folic acid (FA) representing a very small component as an unmetabolized species in blood. We longitudinally evaluated 5-MTHF, FA and total homocysteine in maternal and cord blood from Japanese pregnant women. Subjects were 146 pregnant women who participated in the Chiba study of Mother and Child Health (C-MACH) prospective cohort study. Sera were obtained in early and late pregnancy, at delivery, and from cord blood. Species levels were measured by isotope-dilution mass spectrometry. Both 5-MTHF and FA levels were lower than reported levels from pregnant women in populations from countries with mandatory FA fortification. As gestational age progressed, serum 5-MTHF levels decreased, whereas serum FA levels were slightly reduced only at delivery compared to early pregnancy. A significant negative association between serum 5-MTHF and total homocysteine was shown at all examined times, but no associations with FA were evident. At delivery, cord 5-MTHF was significantly higher than maternal levels, while FA again showed no significant correlation. These results suggest that 5-MTHF is actively transported to the fetus through placental transporters and may reflect folate status during pregnancy as a physiologically important species.

Keywords: 5-methyltetrahydrofolate; cord blood; folic acid; homocysteine; isotope dilution mass spectrometry; pregnant woman; serum folate.

MeSH terms

  • Adult
  • Asian People
  • Female
  • Fetal Blood / metabolism*
  • Folic Acid / blood*
  • Homocysteine / blood
  • Humans
  • Japan
  • Longitudinal Studies
  • Maternal-Fetal Exchange*
  • Placenta / metabolism
  • Pregnancy
  • Pregnant Women*
  • Prospective Studies
  • Tetrahydrofolates / blood*
  • Young Adult


  • Tetrahydrofolates
  • Homocysteine
  • Folic Acid
  • 5-methyltetrahydrofolate