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High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood.
Am J Clin Nutr 2015; 102(4):848-57AJ

Abstract

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.

OBJECTIVES

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.

DESIGN

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.

Authors+Show Affiliations

Departments of Nutritional Sciences and Keenan Research Center for Biomedical Science and.Departments of Nutritional Sciences and Keenan Research Center for Biomedical Science and.Medicine, University of Toronto, Toronto, Ontario, Canada;Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada;Medicine, University of Toronto, Toronto, Ontario, Canada; Keenan Research Center for Biomedical Science and.Freelance statistics consultant, Toronto, Ontario, Canada; and.Department of Obstetrics and Gynecology, St. Michael's Hospital and University of Toronto, Toronto, Canada.Department of Obstetrics and Gynecology, St. Michael's Hospital and University of Toronto, Toronto, Canada.Departments of Nutritional Sciences and Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada;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.

Pub Type(s)

Journal Article
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26269367

Citation

Plumptre, Lesley, et al. "High Concentrations of Folate and Unmetabolized Folic Acid in a Cohort of Pregnant Canadian Women and Umbilical Cord Blood." The American Journal of Clinical Nutrition, vol. 102, no. 4, 2015, pp. 848-57.
Plumptre L, Masih SP, Ly A, et al. High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood. Am J Clin Nutr. 2015;102(4):848-57.
Plumptre, L., Masih, S. P., Ly, A., Aufreiter, S., Sohn, K. J., Croxford, R., ... Kim, Y. I. (2015). High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood. The American Journal of Clinical Nutrition, 102(4), pp. 848-57. doi:10.3945/ajcn.115.110783.
Plumptre L, et al. High Concentrations of Folate and Unmetabolized Folic Acid in a Cohort of Pregnant Canadian Women and Umbilical Cord Blood. Am J Clin Nutr. 2015;102(4):848-57. PubMed PMID: 26269367.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood. AU - Plumptre,Lesley, AU - Masih,Shannon P, AU - Ly,Anna, AU - Aufreiter,Susanne, AU - Sohn,Kyoung-Jin, AU - Croxford,Ruth, AU - Lausman,Andrea Y, AU - Berger,Howard, AU - O'Connor,Deborah L, AU - Kim,Young-In, Y1 - 2015/08/12/ PY - 2015/03/06/received PY - 2015/07/14/accepted PY - 2015/8/14/entrez PY - 2015/8/14/pubmed PY - 2016/1/6/medline KW - cord blood KW - folate KW - folic acid supplementation KW - pregnancy KW - unmetabolized folic acid SP - 848 EP - 57 JF - The American journal of clinical nutrition JO - Am. J. Clin. Nutr. VL - 102 IS - 4 N2 - 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. OBJECTIVES: 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. DESIGN: 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. SN - 1938-3207 UR - https://www.unboundmedicine.com/medline/citation/26269367/High_concentrations_of_folate_and_unmetabolized_folic_acid_in_a_cohort_of_pregnant_Canadian_women_and_umbilical_cord_blood_ L2 - https://academic.oup.com/ajcn/article-lookup/doi/10.3945/ajcn.115.110783 DB - PRIME DP - Unbound Medicine ER -