Concentrations of unmetabolized folic acid and primary folate forms in pregnant women at delivery and in umbilical cord blood

Am J Clin Nutr. 2010 Dec;92(6):1416-22. doi: 10.3945/ajcn.2010.29361. Epub 2010 Sep 15.


Background: The importance of unmetabolized folic acid in maternal and fetal blood is not known.

Objective: We investigated total folate, tetrahydrofolate (THF), 5-methyltetrahydrofolate (5-MTHF), formyl-THF, 5,10-methenylTHF, and folic acid concentrations in women and in umbilical cord blood at delivery.

Design: The study included 87 pregnant women and 29 cord blood samples, including 24 mother-infant pairs. We measured serum concentrations of folate forms by using ultraperformance liquid chromatography-tandem mass spectrometry.

Results: Pregnant women who received 400 μg folic acid daily (n = 25) had higher total folate (P = 0.041), 5-MTHF (P = 0.049), and formyl-THF (P < 0.001) concentrations and slightly higher THF (P = 0.093) concentrations than did nonsupplemented pregnant women (n = 61). We measured folic acid concentrations >0.20 nmol/L in 38 (44%) pregnant women and in 55% of the cord serum samples, but these measurements were not explained by maternal supplement use. Concentrations of folic acid were nonsignificantly higher in cord blood from supplemented women than in cord blood from nonsupplemented women (P = 0.154). Proportions of folic acid to total folate in cord serum did not differ according to maternal supplement usage (0.54% compared with 0.43% in supplemented and nonsupplemented women, respectively). Concentrations of folic acid did not differ between maternal and cord serum. However, folic acid constituted a significantly lower proportion of total folate in cord serum than in maternal serum.

Conclusions: We detected unmetabolized folic acid in more than one-half of cord blood samples. Folic acid (400 μg/d) supplied during pregnancy is not likely to accumulate in the fetus, in contrast to 5-MTHF and THF, which accumulate in the fetus.

MeSH terms

  • Adult
  • Dietary Supplements
  • Female
  • Fetal Blood / chemistry*
  • Folic Acid / administration & dosage*
  • Folic Acid / blood*
  • Formyltetrahydrofolates / blood*
  • Humans
  • Infant, Newborn / blood*
  • Pregnancy / blood*
  • Tetrahydrofolates / blood*
  • Young Adult


  • Formyltetrahydrofolates
  • Tetrahydrofolates
  • Folic Acid