Departments of Nutritional Sciences and Keenan Research Center for Biomedical Science and.
Medicine, University of Toronto, Toronto, Ontario, Canada;
Am J Clin Nutr. 2015 Oct;102(4):848-57. doi: 10.3945/ajcn.115.110783. Epub 2015 Aug 12.
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.
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.
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.
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.
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.
强制性强化、普遍的补充剂使用以及推荐围孕期补充的公共卫生指南增加了北美的孕妇叶酸摄入量。然而，在妊娠期间增加叶酸摄入量对孕妇和脐带血叶酸浓度的影响尚未得到很好的证实。
在这项前瞻性研究中，我们在加拿大孕妇及其新生儿队列中确定了孕妇和脐带血中的叶酸和未代谢叶酸（UMFA）浓度，并研究了母体叶酸和叶酸摄入量以及叶酸代谢中的胎儿遗传变异对叶酸状态的影响。
在孕早期（0-16 周）和孕晚期（23-37 周）评估了 368 名加拿大孕妇的叶酸和叶酸摄入量。使用免疫测定法和液相色谱-质谱法分别测量了母亲样本中的叶酸和 UMFA 浓度，这些样本分别在孕早期（12-16 周）、分娩时（28-42 周）和脐带血中进行了测量。评估了 5,10-亚甲基四氢叶酸还原酶（MTHFR）和二氢叶酸还原酶（DHFR）基因的 4 种胎儿遗传变异与脐带血中叶酸和 UMFA 浓度的关系。
红细胞（RBC）叶酸浓度的几何平均值（95%CI）在孕早期和分娩时分别为 2417 nmol/L（2362，2472 nmol/L）和 2793 nmol/L（2721，2867 nmol/L）。脐带 RBC 叶酸浓度的平均值（95%CI）为 2689 nmol/L（2614，2765 nmol/L）。UMFA 可在>90%的母血和脐血血浆样本中检出。尽管 3 种胎儿 MTHFR 和 DHFR 遗传变异没有影响，但胎儿 MTHFR 677TT 基因型与野生型相比，脐带血清（P=0.03）和脐带 RBC （P=0.02）中的叶酸浓度显著降低。
尽管检测方法存在差异，但母体和脐带 RBC 叶酸和血浆 UMFA 浓度高于先前报道的值。母体和胎儿循环中高叶酸和 UMFA 浓度的功能意义值得进一步研究，因为过量的叶酸状态可能会影响后代的长期健康结果。本研究在 www.clinicaltrials.gov 注册，编号为 NCT02244684。
