Impact of folic acid and active folate supplementation on red blood cell folate levels in patients with unexplained recurrent pregnancy loss and MTHFR 677TT genotype
LU Yongjie,1, HOU Shuchen2, CHANG Liang,1, LIU Ping1
1.State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital; National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital); Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education Beijing; Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
2.Graduate School of Beijing University of Chinese Medicine, Beijing 100029, China
Objective ·To study the effects of folic acid and active folate supplementation on red blood cell folate levels in patients with unexplained recurrent pregnancy loss (URPL) and methylenetetrahydrofolate reductase (MTHFR) 677TT genotype. Methods ·A total of 45 patients with MTHFR 677TT genotype and URPL in the Center for Reproductive Medicine of Peking University Third Hospital from January to December 2021 were selected. They were divided into three groups according to folic acid supplementation, including 16 cases in Group A (who had not received any form of folic acid supplementation before the study began, but received active folic acid supplementation after the study began),15 cases in Group B (who had received ordinary folic acid supplementation before the study began, and active folic acid supplementation after the study began),and 14 cases in Group C (ordinary folic acid was supplemented before the start of the study, and after the start of the study, ordinary folic acid and active folic acid were supplemented together). The concentration of 5-methyltetrahydrofolate (5-MTHF) in red blood cells was measured and compared at the time of enrollment (first measurement) and after supplementation (second measurement). Results ·There was no statistically significant difference in the first measurement of 5-MTHF concentrations in red blood cells between any two groups of patients in the three groups. Compared with the first measurement of 5-MTHF concentrations in red blood cells, the second increased (all P=0.000); the increase in 5-MTHF concentrations in red blood cells in Group B was higher than that in Group A (all P=0.000); the increasing 5-MTHF concentration in Group B was higher than that in Group A (t=2.373, P=0.049), but there was no significant difference between Group B and Group C. Conclusion ·Compared with folic acid supplementation, active folate supplementation can better improve red blood cell folate levels in patients with MTHFR 677TT genotype and URPL in a short period.
LU Yongjie, HOU Shuchen, CHANG Liang, LIU Ping. Impact of folic acid and active folate supplementation on red blood cell folate levels in patients with unexplained recurrent pregnancy loss and MTHFR 677TT genotype. Journal of Shanghai Jiao Tong University (Medical Science)[J], 2024, 44(6): 741-745 doi:10.3969/j.issn.1674-8115.2024.06.009
分别于入组时（第一次）和入组按计划补充叶酸后（第二次），采用液相色谱-串联质谱联用（liquid chromatography-tandem mass spectrometry，LC-MS/MS）技术对3组患者的红细胞5-MTHF浓度进行检测［15］。将第一次、第二次的红细胞5-MTHF浓度分别记为浓度1和浓度2。A组、B组、C组中，第二次与第一次红细胞5-MTHF浓度的差值分别计为ΔA、ΔB、ΔC。
LU Yongjie analyzed the clinical data and wrote the manuscript. HOU Shuchen collected the clinical data. CHANG Liang designed the study and wrote the manuscript. LIU Ping revised the manuscript. All the authors have read the last version of paper and consented for submission.
利益冲突声明
所有作者声明不存在利益冲突。
COMPETING INTERESTS
All authors disclose no relevant conflict of interests.
GREEN D M, O'DONOGHUE K. A review of reproductive outcomes of women with two consecutive miscarriages and no living child[J]. J Obstet Gynaecol, 2019, 39(6): 816-821.
VAN DIJK M M, KOLTE A M, LIMPENS J, et al. Recurrent pregnancy loss: diagnostic workup after two or three pregnancy losses? A systematic review of the literature and meta-analysis[J]. Hum Reprod Update, 2020, 26(3): 356-367.
ZHAO Y F, ZHOU T. Risk factors of recurrent spontaneous abortion among women of childbearing age: a logistic regression analysis[J]. Modern Preventive Medicine, 2019, 46(7): 1153-1155, 1175.
FAN J L. The effect of dydrogesterone and human chorionic gonadotropin in the treatment of unexplained habitual miscarriage[J]. Practical Clinical Journal of Integrated Traditional Chinese and Western Medicine, 2020, 20(5): 84-85.
KANASAKI K, KUMAGAI A. The impact of micronutrient deficiency on pregnancy complications and development origin of health and disease[J]. J Obstet Gynaecol Res, 2021, 47(6): 1965-1972.
RUSHING B R, FOGLE H M, SHARMA J, et al. Exploratory metabolomics underscores the folate enzyme ALDH1L1 as a regulator of glycine and methylation reactions[J]. Molecules, 2022, 27(23): 8394.
ZARFESHAN FARD Y, KOOSHKAKI O, KORDI TAMMANDANI D, et al. Investigation of the association between C677T polymorphism of the MTHFR gene and plasma homocysteine level in recurrent fetal miscarriage[J]. J Obstet And Gynaecol, 2019, 45(8): 1442-1447.
MO H, RAO M, WANG G, et al. Polymorphism of MTHFR 1298A>C in relation to adverse pregnancy outcomes in Chinese populations[J]. Mol Genet Genomic Med, 2019, 7(5): e642.
SAYYAH-MELLI M, GHORBANIHAGHJO A, ALIZADEH M, et al. The effect of high dose folic acid throughout pregnancy on homocysteine (Hcy) concentration and pre-eclampsia: a randomized clinical trial[J]. PLoS One, 2016, 11(5): e0154400.
VAN DER LINDEN I J, AFMAN L A, HEIL S G, et al. Genetic variation in genes of folate metabolism and neural-tube defect risk[J]. Proc Nutr Soc, 2006, 65(2): 204-215.
SOWMYA S, AYYALI A, KR V, et al. Genetic variation of folate metabolic pathway in recurrent pregnancy loss: a systematic review[J]. Int J Med Rev Case Rep, 2022, 6(19): 50-53.
WANG X, THOMAS P, XUE J L, et al. Folate deficiency induces aneuploidy in human lymphocytes in vitro-evidence using cytokinesis-blocked cells and probes specific for chromosomes 17 and 21[J]. Mutat Res, 2004, 551(1/2): 167-180.
HAO L, YANG Q H, LI Z, et al. Folate status and homocysteine response to folic acid doses and withdrawal among young Chinese women in a large-scale randomized double-blind trial[J]. Am J Clin Nutr, 2008, 88(2): 448-457.
CRIDER K S, ZHU J H, HAO L, et al. MTHFR 677C→T genotype is associated with folate and homocysteine concentrations in a large, population-based, double-blind trial of folic acid supplementation[J]. Am J Clin Nutr, 2011, 93(6): 1365-1372.
BOR M V, WULFF A M, NEXO E, et al. Infrequency of low red blood cell (RBC) folate levels despite no folate fortification program: a study based on results from routine requests for RBC folate[J]. Clin Chem Lab Med, 2008, 46(3): 401-404.
MEI J, WANG H, LU S, et al. Treatment effect of active folate on adverse pregnancy[J]. Chinese Journal of Woman and Child Health Research, 2017, 28(12): 1659-1661.
