High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood.
BACKGROUND
Mandatory fortification, prevalent supplement use, and public health guidelines recommending periconceptional supplementation have increased folic acid intakes in North American pregnant women. However, the effects of increased folic acid intakes during pregnancy on maternal and cord blood folate concentrations have not been well established.


OBJECTIVE
In this prospective study, we determined maternal and cord blood concentrations of folate and unmetabolized folic acid (UMFA) in a cohort of pregnant Canadian women and their newborns and examined the effect of maternal intakes of folate and folic acid and fetal genetic variants in folate metabolism on folate status.


METHODS
Folate and folic acid intakes of 368 Canadian pregnant women were assessed in early (0-16 wk) and late (23-37 wk) pregnancy. Blood concentrations of folate and UMFA were measured with the use of immunoassays and liquid chromatography-mass spectrometry, respectively, in maternal samples in early pregnancy (12-16 wk), at delivery (28-42 wk), and in cord blood. Four fetal genetic variants of the 5,10-methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR) genes were assessed for their association with cord blood concentrations of folate and UMFA.


RESULTS
Geometric mean (95% CI) maternal red blood cell (RBC) folate concentrations were 2417 nmol/L (2362, 2472 nmol/L ) and 2793 nmol/L (2721, 2867 nmol/L ) in early pregnancy and at delivery, respectively. The mean (95% CI) cord RBC folate concentration was 2689 nmol/L (2614, 2765 nmol/L). UMFA was detectable in >90% of maternal and cord plasma samples. Although 3 fetal MTHFR and DHFR genetic variants had no effect, the fetal MTHFR 677TT genotype was associated with significantly lower cord serum (P = 0.03) and higher cord RBC (P = 0.02) folate concentrations than those of the wild type.


CONCLUSIONS
Notwithstanding differences in assays, maternal and cord RBC folate and plasma UMFA concentrations were higher than previously reported values. Functional ramifications of high folate and UMFA concentrations in maternal and fetal circulation warrant additional investigation because an excess folate status may affect long-term health outcomes of the offspring. This study was registered at www.clinicaltrials.gov as NCT02244684.
Departments of Nutritional Sciences and Keenan Research Center for Biomedical Science and.
Lesley
L
Plumptre
Departments of Nutritional Sciences and Keenan Research Center for Biomedical Science and.
Shannon P
SP
Masih
Medicine, University of Toronto, Toronto, Ontario, Canada;
Anna
A
Ly
Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada;
Susanne
S
Aufreiter
Medicine, University of Toronto, Toronto, Ontario, Canada; Keenan Research Center for Biomedical Science and.
Kyoung-Jin
KJ
Sohn
Freelance statistics consultant, Toronto, Ontario, Canada; and.
Ruth
R
Croxford
Department of Obstetrics and Gynecology, St. Michael's Hospital and University of Toronto, Toronto, Canada.
Andrea Y
AY
Lausman
Department of Obstetrics and Gynecology, St. Michael's Hospital and University of Toronto, Toronto, Canada.
Howard
H
Berger
Departments of Nutritional Sciences and Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada;
Deborah L
DL
O'Connor
Departments of Nutritional Sciences and Medicine, University of Toronto, Toronto, Ontario, Canada; Keenan Research Center for Biomedical Science and Division of Gastroenterology, Department of Medicine, St. Michael's Hospital, Toronto, Canada; youngin.kim@utoronto.ca.
Young-In
YI
Kim
D000328:Adult; D002170:Canada; D019587:Dietary Supplements; D002149:Energy Intake; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D005492:Folic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D016015:Logistic Models; D039382:Maternal Nutritional Physiological Phenomena; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D015596:Nutrition Assessment; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011446:Prospective Studies; D011795:Surveys and Questionnaires; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D006710:Homocysteine; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013762:Tetrahydrofolate Dehydrogenase
cord blood; folate; folic acid supplementation; pregnancy; unmetabolized folic acid