Journal of Nutrition and Health

The Korean Nutrition Society (한국영양학회)
권호 표지

Effects of Maternal Serum B vitamins, Homocysteine Concentrations and the 5, 10-Methylenetetrahydrofolate Reductase (MTHFR) Polymorphism on Pregnancy Outcomes

임신부의 혈청 비타민 B 수준과 혈중 호모시스테인 수준 및 MTHFR 유전자형이 임신 결과에 미치는 영향

  • 김기남 (이화여자대학교 생활환경대학 식품영양학과) ;
  • 김영주 (이화여자대학교 의과대학 산부인과학교실) ;
  • 박혜숙 (이화여자대학교 의과대학 예방의학교실) ;
  • 장남수 (이화여자대학교 생활환경대학 식품영양학과)
  • Published : 2003.05.01
Download PDF
⟨ Previous Next ⟩

Abstract

Maternal nutritional status has been shown to influence pregnancy outcomes. And the elevated maternal plasma homocysteine concentrations have been associated with adverse pregnancy outcomes. We investigated the effects of maternal serum levels of B vitamins and homocysteine, and the C677T MTHFR (5, 10-methylenetetrahydrofolate reductase) polymorphism on pregnancy outcomes. In 177 pregnant women of 24-28 wks of gestation, the MTHFR gene mutation, serum B vitamins and homocysteine concentrations were measured, and their pregnancy outcomes were investigated from medical records. The birth length, and 1- and 5-min Apgar scores of neonates in the T/T mothers were 45.4 $\pm$ 9.3 cm, 7.6 $\pm$ 3.2 and 8.5 $\pm$ 3.8, respectively, which were significantly lower than those in the C/T (48.6 $\pm$ 3.3 cm, 9.0 $\pm$ 0.2, 10.0 $\pm$ 0.2) or the C/C mothers (49.4 $\pm$ 1.9 cm, 9.0 $\pm$ 0.2, 10.0 $\pm$ 0.0). The birth weight, birth length and the gestational age of neonates at delivery from hyperhomocysteinemic mothers whose homocysteine levels higher than 15 $\mu$ mol were 2.5 $\pm$ 1.3 kg, 43.9 $\pm$ 9.0 cm, 35.4 $\pm$ 6.3 wk, respectively, which were significant lower than those from normohomocysteinemic mothers (3.1 $\pm$ 0.6 kg, 48.8 $\pm$ 3.6 cm, 38.5 $\pm$ 2.5 wk). The birth weight and birth length of neonates in mothers whose PLP levels were below the median were significantly lower than those from mothers with the PLP levels above the median. The 1- and 5-min Apgar scores of neonates were lower in mothers with the T/T MTHFR genotype than those with the C/T or C/C only when the serum PLP levels were below the median. The 1-, 5 min Apgar scores and birth length of neonates were lower in mothers with the T/T MTHFR genotype than those with the C/T or C/C only when the serum FMN levels were below the median. In conclusion, maternal B vitamin status, homocysteine and the C677T MTHFR genotype seem to have played an important role on pregnancy outcomes.

Keywords

References

  1. Walker MC, Smith GN, Perkins SL, Keely EJ, Garner PR. Changes in homocysteine levels during normal pregnancy. Am J Obstet Gynecol 180: 660-664, 1999 https://doi.org/10.1016/S0002-9378(99)70269-3
  2. Burke G, Robinson K, Refsum H, Stuart B, Drumm J, Graham I. Intrauterine growth retardation, perinatal death, and maternal homocysteine levels. N Engl J Med 326: 69-70, 1992
  3. Mill JL, McPartlin JM, Kirke PN. Homocysteine metabolism in pregnancies complicated by neural tube defects. Lancet 345: 149-151, 1995 https://doi.org/10.1016/S0140-6736(95)90165-5
  4. Rosenquist TH, Ratashak SA, Selhub J. Homocysteine induces congenital defects of the heart and neural tube: effect of folic acid. Proc Natl Acad Sci USA 93: 15227-15232, 1995 https://doi.org/10.1073/pnas.93.26.15227
  5. Aubard Y, Darodes N, Cantaloube M. Hyperhomocysteinemia and pregnancy-review of our present understanding and therapeutic implications. Eur J Obstet Gynecol 93: 157-165, 2000 https://doi.org/10.1016/S0301-2115(00)00282-7
  6. Scholl TO, Johnson WG. Folic acid: influence on the outcome of pregnancy. Am J Clin Nutr 71: 1295S-1303S, 2000
  7. Wouters MG, Boers GH, Blom HJ, Trijbels FJ, Thomas CM, Borm GF, Steegers-Theunissen RP and Eskes TK. Hyperhomocysteinemia: A risk factor in women with unexplained recurrent early pregnancy loss. Fertil Steril 60: 820-825, 1993
  8. Leena M, Riyazi N, de Vries JIP, Jakobs C, van Geijn HP, Dekker GA. Effects of folic acid and vitamin <TEX>$B_6$</TEX> supplementation on women with hyperhomocysteinemia and a history of preeclampsia or fetal growth restriction. Am J Obstet Gynecol 179: 135-139, 1998 https://doi.org/10.1016/S0002-9378(98)70263-7
  9. Goddijn-Wessel TAW, Wouters MGAJ, v.d. Molen EF, Spuijbroek MDEH, Steegers-Theunissen RPM, Blom HJ, Boers GHJ Eskes TKAB. Hyperhomocysteinemia: A risk factor for placental abruption or infarction. Eur J Obstet Gynecol 66: 23-29, 1996 https://doi.org/10.1016/0301-2115(96)02383-4
  10. Kang SS, Wong PWK, Cook HY, Norusis M, Messer JV. Protein-bound homocyst (e) ine. J Clin Invest 77: 1482-1486, 1986 https://doi.org/10.1172/JCI112461
  11. Rady PL, Szucs S, Grady J, Hudnall SD, Kellner LH, Nitowsky H, Tyring SK, Matalon RK. Genetic Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) in ethnic populations in Texas; A report of a novel MTHFR polymorphic site, G1793A. Am J Med Genet 107: 162-168. 2002 https://doi.org/10.1002/ajmg.10122
  12. van der Put NMJ, Blom HJ. Neural tube defects and a disturbed folate dependent homocyssteine metabolism. Eur J Obstet Gunecol Reprod Biol 92 : 57-61, 2000 https://doi.org/10.1016/S0301-2115(00)00426-7
  13. Gaughan DJ, Kluijtmans LA, Barbaux S, McMaster D, Young IS, Yarnell JW, Evans A, Whitehead AS. The methionine synthase reductase (MTRR) A66G polymorphism is a novel genetic determinant of plasma homocysteine concentrations. Atherosclerosis 157: 451-456, 2001 https://doi.org/10.1016/S0021-9150(00)00739-5
  14. Chango A, Emery-Fillon N, de Courcy GP, Lambert D, Pfister M, Rosenblatt DS, Nicolas JP. A polymorphism (80G→A) in the reduced folate carrier gene and its associations with folate status and homocysteinemia. Mol Genet Metab 70: 310-315, 2000 https://doi.org/10.1006/mgme.2000.3034
  15. Perry DJ. Hyperhomocysteinaemia. Baillieres Clin Heamatol 12: 451-477, 1999
  16. Ueland PM, Hustad S, Schneede J, Refsum H, Vollset SE. Biological and clinical implications of the MTHFR C677T polymorphism. Trends in Pharmacol Sci 22: 195-201, 2001 https://doi.org/10.1016/S0165-6147(00)01675-8
  17. Ahn HS, Lee GJ, Kim YT. Relationship between vitamin $B_6$ status of maternal-umbilical cord plasma and pregnancy outcomes. Korean J Nutr 33(3): 263-270, 2000
  18. Ahn HS, Lee GJ, Chung HW. Maternal vitamin B6 intake and vitamin $B_6$ level in maternal, umbilical cord plasma and placenta. Korean J Nutr 35: 322-331, 2002
  19. Ahn HS, Kim JS, Lee GJ, Kim YT. Serum folate levels of maternal-umbilical cord blood and pregnancy outcomes. Korean J Nutr 33(8): 840-847, 2000
  20. Araki A, Sako Y. Determination of free and total homocysteine in human plasma by high performance liquid chromatography with fluorescence detection. J Chromatogr 422: 43-52, 1987 https://doi.org/10.1016/0378-4347(87)80438-3
  21. Botticher B, Botticher D. A new HPLC-method for the simultaneous determination of $B_{1^-}$, $B_{2^-}$ and $B_{6^-}$vitamers in serum and whole blood. Int J Vitam Nutr Res 57: 273-298, 1987
  22. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard C, Matthews R. Boers GJ, den Heijer M, Kluijtmans LA, van den Heuvel LP, Rozen R. A candidate genetic risk factor for vascular disease: A common mutation in methylenetetrahydrofolate reductase. Nat Genet lO: 111-113, 1995 https://doi.org/10.1038/ng0595-111
  23. Picciano MF. Is homocysteine a biomarker for identifying women at risk of complications and adverse pregnancy outcomes? Am J Clin Nutr 71: 857-858, 2000
  24. Bondevik GT, Schneede J, Refsum H, Lie RT, Ulstein M, Kvale G. Homocysteine and methylmalonic acid levels in pregnant Nepali women. Should cobalamin supplementation be considered? Eur J Clin Nutr 55: 856-864, 2001 https://doi.org/10.1038/sj.ejcn.1601236
  25. Vollset SE, Refsum H, Irgens LM, Emblem BM, Tverdal A, Gjessing HK, Monsen ALB, Ueland PM. Plasma total homocysteine, pregnancy complications and adverse pregnancy outcomes: the Hordaland Homocysteine Study. Am J Clin Nutr 71 : 962-968, 2000
  26. Khong TY, Hague WM. The placenta in maternal hyperhomocysteinaemia. Br J Obstet Gynaecol 106(3): 273-278, 1999 https://doi.org/10.1111/j.1471-0528.1999.tb08243.x
  27. Locksmith GJ, Duff P. Preventing neural tube defects: the importance of periconceptional folic acid supplements. Obstet Gynecol 91: 1027-1034, 1998 https://doi.org/10.1016/S0029-7844(98)00060-X
  28. Chambers JC, McGregor A, Jean-Marie J, Kooner JS. Acute hyperhomocysteinaemia and endothelial dysfunction. Lancet 351: 35, 1998 https://doi.org/10.1016/S0140-6736(05)78090-9
  29. Alfirevic Z, Mousa HA, Martlew V, Briscoe L, Perez-Casal M, Toh CH. Postnatal screening for thrombophilia in women with severe pregnancy complications. Obstet Gynecol 97 (5 Pt 1): 753-9, 2001 https://doi.org/10.1016/S0029-7844(01)01190-5
  30. Gebhardt GS, Scholtz CL, Hillermann R, Odendaal HJ. Combined heterozygosity for methylenetetrahydrofolate reductase (MTHFR) mutations C677T and A1298C is associated with abruptio placentae but not with intrauterine growth restriction. Eur J Obstet Gynecol Reprod Biol 97(2): 174-177, 2001 https://doi.org/10.1016/S0301-2115(00)00540-6
  31. Cikot RJLM, Steegers-Theunissen RPM, Thomas CMG, de Boo TM, Merkus HMWM, Steegers EAP. Longitudinal vitamin and homocysteine levels in normal pregnancy. Br J Nutr 85: 49-58, 2001 https://doi.org/10.1079/BJN2000209
  32. Schuster K, Bailey LB, Mahan CS. Effect of maternal pyridoxine X HCl supplementation on the vitamin B-6 status of mother and infant and on pregnancy outcome. J Nutr 114(5): 977-988, 1984
  33. Schuster K, Bailey LB, Mahan CS. Vitamin $B_6$ status of lowincome adolescent and adult pregnant women and the condition of their infants at birth. Am J Clin Nutr 34(9): 1731-1735, 1981
  34. Bruinse HW, van den Berg H. Changes of some vitamin levels during and after normal pregnancy. Eur J Obstet Gynecol 61: 31-37, 1995 https://doi.org/10.1016/0028-2243(95)02150-Q
  35. van den Berg M, Franken DG, Boers GHJ, Blom HJ, Jakobs C, Stehouwer CDA, Rauwerda JA. Combined vitamin $B_6$ plus folic acid therapy in young patients with arteriosclerosis and hyperhomocysteinemia. J Vasc Surg 20: 933-940, 1994 https://doi.org/10.1016/0741-5214(94)90230-5
  36. Bates CJ, Fuller NJ. The effect of riboflavin deficiency on methylenetetrahydrofolate reductase (NADPH) (EC 1.5.1.20) and folate metabolism in the rat. Br J Nutr 55: 455-464, 1986 https://doi.org/10.1079/BJN19860051
  37. Hustad S, Ueland PM, Vollset SE, Zhang Y, Bjorke-Monsen AL, Schneede J. Riboflavin as a determinant of plasma total homocysteine: effect modification by the methylenetetrahydrofolate reductase C677T polymorphism. Clin. Chem 46(8 Pt 1): 1065-1071, 2000
  38. McNulty H, McKinley MC, Wilson B, McPartlin J, Strain JJ, Weir DG, Scott JM. Impaired functioning of thermolabile methylenetetrahydrofolate reductase is dependent on riboflavin status: implications for riboflavin requirements. Am J Clin Nutr 76: 436-441, 2002
  39. Jacques PF, Kambach R, Bagley P, Russo GT, Rogers G, Wilson PWF, Roseberg IH, Selhub J. The relationship between riboflavin and plasma total homocysteine in the Framingham offspring cohort is influenced by folate status and the C677T transition in the methylentetrahydrofolate reductase gene. J Nutr 132: 283-288, 2002