The Association of Serum Levels of Folic Acid and Homocysteine in Pregnant Women with Pre-Eclampsia

Document Type : Original Article


1 Resident of Obstetrics and Gynecology, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran.

2 Ph.D. Student of Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.

3 B.Sc. of Biotechnology, Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.

4 Assistant Professor, Department of Biochemistry, Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.

5 Assistant Professor, Department of Obstetrics and Gynecology, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran.


Introduction: Pre-eclampsia is one of the main cause of death in pregnant mothers and their babies, but its cause is still unknown. Studies have shown that increased maternal homocysteine ​​in the blood is associated with various diseases such as pre-eclampsia. For inhibition from serum homocysteine elevation, high dose folic acid can be prescribed in these cases. This study aimed to assess the association of serum levels of folic acid and homocysteine with pre-eclampsia.
Methods: This case-control study was conducted on 125 women with pre-eclampsia and 125 healthy pregnant women referred to Hajar hospital of Shahrekord, Iran during 2011-2012. 5 ml of blood sample was taken and serum levels of folic acid and homocysteine ​​were measured. Data were analyzed using SPSS software version 20 and t-test, chi-square, two-way ANOVA and correlation regresion. P value less than 0.05 was considered significant.
Results: Mean levels of homocysteine were elevated in cases with pre-eclampsia compared to control group (p=0.01) (11.27±4.8 vs. 9.9±3.9 µmol/l) and mean level of folic acid were significantly lower in cases with pre-eclampsia (p=0.002) (9.96±4.3 vs. 8.39±3.6 ng/ml). BMI, age, gestational age and neonatal weight have been shown to be different statistically in two groups (p<0.001) and other variables such as education level revealed no significant differences between two groups (p=0.257).
Conclusion: Mothers with high serum levels of homocysteine and folic acid and high age and BMI are more at risk of pre-eclampsia. It seems that upper dose of folic acid can prevent or decrease the risk of pre-eclampsia.


  1. Saftlas AF, Olson DR, Franks L, Atrash HK, Pokras R. Epidemiology of preeclampsia and eclampsia in the United States, 1979-1986. Am J Obstet Gynecol 1990 Aug;163(2):460-5.
  2. Barron WM, Murphy MB, Lindheimer MD. Management of hypertension during pregnancy. In: Laragh GH, Brenner BM, editors. Hypertension: pathophysiology, diagnosis and management. New York:Raven;1990:1809-27.
  3. National high blood pressure education program working group report on high blood pressure in pregnancy. Am J Obstet Gynecol 1990 Nov;163(5 Pt 1):1691-1712.
  4. Cunningham FG, Leveno KJ, Bloom SL, HauthJC, Rouse DJ, Spong CY. Williams obstetrics. 23rd ed. New York:McGraw-Hill;2010:706-56.
  5. Stiefel P, Miranda ML, Behhido LM, Luna J, Jimenez L, Pamies E, et al. Genotype of the CYBA promoter930A/G, Polymorphism C677T of the MTHFR and APOE genotype in patient with hypertensive disorders of pregnancy: an observational study. Med Clin (Barc) 2009 Nov 7;133(17):657-61.
  6. Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Fastad M, Vollset SE. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 1997 Jul;337(4):230-6.
  7. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a metaanalysis. BMJ 2002 Nov 23;325(7374):1202-6.
  8. Voutilainen S, Rissanen TH, Virtanen J, Lakka TA, Salonen JT. Low dietary folic acid intake is associated with an excess incidence of acute coronary events: the Kuopio Ischemic Heart Disease Risk Factor Study. Circulation 2001 Jun 5;103(22):2674-80.
  9. Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ, Schouten EG. MTHFR 677C-- T polymorphism and risk of coronary heart disease: a meta-analysis. J Am Med Assoc 2002 Oct 23-30;288(16):2023-31.
  10. Durga J, Bots ML, Schouten EG, Kok FJ, Verhoef P. Low concentrations of folic acid, not hyperhomocysteinemia, are associated with carotid intima-media thickness. Atherosclerosis 2005 Apr;179(2):285-92.
  11. Nadafi M, Mohammad Hosseini S, Afrasiabyfar A, Momeni E, Malekzadeh GM. [Association of homocysteine,vitamin and blood factors with preeclampsia in pregnant women] [Article in Persian]. Armaghan Danesh 2009;15(2(58)):171-80
  12. Katre P, Bhat D, Lubree H, Otiv S, Joshi S, Joglekar C, et al. Vitamin B12 and folic acid supplementation and plasma total homocysteine concentrations in pregnant Indian women with low B12 and high folate status. Asia Pac J Clin Nutr 2010;19(3):335-43.
  13. Bánhidy F, Dakhlaoui A, Dudás I, Czeizel AE. Birth outcomes of newborns after folic acid supplementation in pregnant women with early and late pre-eclampsia: a population-based study. Adv Prev Med 2011;2011:127369 .
  14. Begum JA , Chowdhury TA, Biswas KB, Ali L. Vitamin B12 and folate status in preeclamptic women in Bangladesh. BJMS 2009;15(2):83-6.
  15. Hoffman ML, Scoccia B, Kurczynski TW, Shulman LP, Gao W. Abnormal folate metabolism as a risk factor for first-trimester spontaneous abortion. J Reprod Med 2008 Mar;53(3):207-12.
  16. Kawai K, Spiegelman D, Shankar AH, Fawzi WW. Maternal multiple micronutrient supplementation and pregnancy outcomes in developing countries: meta-analysis and meta-regression. Bull World Health Organ 201 Jun 1;89(6):402-11B.
  17. Acilmis YG, Dikensoy E, Kutlar AL, Balat O, Cebesoy FB, Ozturk E, et al. Homocysteine, folic acid and vitamin B12 levels in maternal and umbilical cord Plasma and homocysteine levels in placenta in pregnant women with pre-eclampsia. J Obstet Gynaecol Res 2011 Jan;37(1):45-50.
  18. Pi-Sunyer FX. Medical hazards of obesity. Ann Intern Med 2000;160:2847-53.
  19. Fernandez M, Fernandez G, Diez-Ewald M, Torres E, Vizcaino G, Fernandez N, et al. [Plasma homocysteine concentrations and its relationship with the development of preeclampsia. Effect of prenatal administration of folic acid] [Article in Spanish]. Invest Clin 2005 Jun;46(2):187-95.
  20. Walker MC, Smith GN, Perkins SL, Keely EJ, Garner PR. Changes in homocysteine levels during normal pregnancy. Am J Obstet Gynecol 1999 Mar;180(3 Pt 1):660-4.
  21. Hogg BB, Tamura T, Johnston KE, Dubard MB, Goldenberg RL. Second-trimester plasma homocysteine levels and pregnancy-induced hypertension, preeclampsia, and intrauterine growth restriction. Am J Obstet Gynecol 2000 Oct;183(4):805-9.
  22. Vollset SE, Refsum H, Irgens LM, Emblem BM, Tverdal A, Gjessing HK, et al. Plasma total homocysteine, pregnancy complications, and adverse pregnancy outcomes: the Hordaland Homocysteine study. Am J Clin Nutr 2000 Apr;71(4):962-8.
  23. Bostom AG, Lathrop L. Homocysteinemia in end-stage renal disease: prevalence, etiology, and potential relationship to arteriosclerotic outcomes. Kidney Int 1997 Jul;52(1):10-20.
  24. Carmel R. Ethnic and racial factors in cobalamin metabolism and its disorders. Semin Hematol 1999 Jan;36(1):88-100.
  25. Mignini LE, Latthe PM, Villar J, Kilby MD, Carroli G, Khan K. Mapping the theories of preeclampsia: the role of homocysteine. Obstet Gynecol 2005 Feb;105(2):411-25.
  26. Finkelstein JD. Methionine metabolism in mammals. J Nutr Biochem 1990 May;1(5):228-37.
  27. Erdemoglu E, Ugr M, Erdemoglu E. Plasma homocysteine and nitric oxide levels in Preeclampsia. Turk German Gynecol 2009;10:26-9.