Comparison of high dose and low dose folic acid supplementation on prevalence, onset and severity of preeclampsia

Shahraki, Azar Danesh; Dehkordi, Nastaran Zamani; Lotfizadeh, Masoud

Comparison of high dose and low dose folic acid supplementation on prevalence, onset and severity of preeclampsia

Document Type : Original Article

Authors

¹ Department of Obstetrics and Gynecology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, I.R., Iran

² Department of Community Health, Social Health Determinants Research Center, Shahrekord University of Medical Sciences, Shahrekord, I.R., Iran

Abstract

Background: Folic acid supplementation had previously mentioned as a protective factor against the onset of preeclampsia (PE). In this study, we aimed to compare the effect of high dose (5 mg daily) and low dose (1 mg daily) of folic acid supplementation on prevalence, onset and severity of PE.
Materials and Methods: Pregnant women who were in the first trimester and referred to prenatal care university hospitals of Isfahan, Iran during October 2013–May 2015 were included in this study, then they were randomly divided into two groups of 5 mg and 1 mg (treated with daily 5 mg and 1 mg of folic acid, respectively), both groups received folic acid from the first trimester of pregnancy to 42 days after termination. Blood pressure, body mass index (BMI), and some urine and blood biochemistry parameters were measured. SPSS-22 used for statistical analysis.
Results: A total of 943 pregnant women participated in the study (450 women in 1 mg group and 450 women in 5 mg group). Incidence rate of PE was 3.8% in 1 mg group and 2.4% in 5 mg group. In a comparison of preeclamptic patients in 1 mg and 5 mg group, no significant differences were seen regarding age, BMI, laboratory data, the severity of the disease, and onset (early or late) (P > 0.05).
Conclusion: Although our findings support that administration of high dose folic acid may decrease the prevalence of PE, there is not enough data to support that higher amount of folic acid administration can reduce the severity of presentation's signs or ameliorate the laboratory data and the onset of PE.

Keywords

References

1.	MacKay AP, Berg CJ, Atrash HK. Pregnancy-related mortality from preeclampsia and eclampsia. Obstet Gynecol 2001;97:533-8.
2.	Garovic VD, Bailey KR, Boerwinkle E, Hunt SC, Weder AB, Curb D, et al. Hypertension in pregnancy as a risk factor for cardiovascular disease later in life. J Hypertens 2010;28:826-33.
3.	Magnussen EB, Vatten LJ, Smith GD, Romundstad PR. Hypertensive disorders in pregnancy and subsequently measured cardiovascular risk factors. Obstet Gynecol 2009;114:961-70.
4.	Roberts JM, Pearson G, Cutler J, Lindheimer M; NHLBI Working Group on Research on Hypertension During Pregnancy. Summary of the NHLBI Working Group on research on hypertension during pregnancy. Hypertension 2003;41:437-45.
5.	American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol 2013;122:1122-31.
6.	Roberts JM, Gammill HS. Preeclampsia: Recent insights. Hypertension 2005;46:1243-9.
7.	Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet 2010;376:631-44.
8.	Campbell OM, Graham WJ; Lancet Maternal Survival Series Steering Group. Strategies for reducing maternal mortality: Getting on with what works. Lancet 2006;368:1284-99.
9.	Bodnar LM, Tang G, Ness RB, Harger G, Roberts JM. Periconceptional multivitamin use reduces the risk of preeclampsia. Am J Epidemiol 2006;164:470-7.
10.	Rumbold AR, Crowther CA, Haslam RR, Dekker GA, Robinson JS; ACTS Study Group. Vitamins C and E and the risks of preeclampsia and perinatal complications. N Engl J Med 2006;354:1796-806.
11.	Merchant AT, Msamanga G, Villamor E, Saathoff E, O'brien M, Hertzmark E, et al. Multivitamin supplementation of HIV-positive women during pregnancy reduces hypertension. J Nutr 2005;135:1776-81.
12.	Poston L, Briley AL, Seed PT, Kelly FJ, Shennan AH; Vitamins in Pre-eclampsia (VIP) Trial Consortium. Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): Randomised placebo-controlled trial. Lancet 2006;367:1145-54.
13.	Olsen SF, Secher NJ. A possible preventive effect of low-dose fish oil on early delivery and pre-eclampsia: Indications from a 50-year-old controlled trial. Br J Nutr 1990;64:599-609.
14.	Murakami S, Matsubara N, Saitoh M, Miyakaw S, Shoji M, Kubo T. The relation between plasma homocysteine concentration and methylenetetrahydrofolate reductase gene polymorphism in pregnant women. J Obstet Gynaecol Res 2001;27:349-52.
15.	Cotter AM, Molloy AM, Scott JM, Daly SF. Elevated plasma homocysteine in early pregnancy: A risk factor for the development of severe preeclampsia. Am J Obstet Gynecol 2001;185:781-5.
16.	Cotter AM, Molloy AM, Scott JM, Daly SF. Elevated plasma homocysteine in early pregnancy: A risk factor for the development of nonsevere preeclampsia. Am J Obstet Gynecol 2003;189:391-4.
17.	D'Anna R, Baviera G, Corrado F, Ientile R, Granese D, Stella NC. Plasma homocysteine in early and late pregnancies complicated with preeclampsia and isolated intrauterine growth restriction. Acta Obstet Gynecol Scand 2004;83:155-8.
18.	Makedos G, Papanicolaou A, Hitoglou A, Kalogiannidis I, Makedos A, Vrazioti V, et al. Homocysteine, folic acid and B12 serum levels in pregnancy complicated with preeclampsia. Arch Gynecol Obstet 2007;275:121-4.
19.	Onalan R, Onalan G, Gunenc Z, Karabulut E. Combining 2^nd-trimester maternal serum homocysteine levels and uterine artery Doppler for prediction of preeclampsia and isolated intrauterine growth restriction. Gynecol Obstet Invest 2006;61:142-8.
20.	Sorensen TK, Malinow MR, Williams MA, King IB, Luthy DA. Elevated second-trimester serum homocyst(e) ine levels and subsequent risk of preeclampsia. Gynecol Obstet Invest 1999;48:98-103.
21.	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;71:962-8.
22.	Mujawar SA, Patil VW, Daver RG. Study of serum homocysteine, folic acid and vitamin B(12) in patients with preeclampsia. Indian J Clin Biochem 2011;26:257-60.
23.	Prevention of neural tube defects: Results of the medical research council vitamin study. MRC Vitamin Study Research Group. Lancet 1991;338:131-7.
24.	Czeizel AE, Dudás I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 1992;327:1832-5.
25.	Lowering blood homocysteine with folic acid based supplements: Meta-analysis of randomised trials. Homocysteine Lowering Trialists' Collaboration. BMJ 1998;316:894-8.
26.	Olthof MR, Bots ML, Katan MB, Verhoef P. Effect of folic acid and betaine supplementation on flow-mediated dilation: A randomized, controlled study in healthy volunteers. PLoS Clin Trials 2006;1:e10.
27.	Ray JG, Laskin CA. Folic acid and homocyst(e) ine metabolic defects and the risk of placental abruption, pre-eclampsia and spontaneous pregnancy loss: A systematic review. Placenta 1999;20:519-29.
28.	Bilano VL, Ota E, Ganchimeg T, Mori R, Souza JP. Risk factors of pre-eclampsia/eclampsia and its adverse outcomes in low- and middle-income countries: A WHO secondary analysis. PLoS One 2014;9:e91198.
29.	Zareian Z. Hypertensive disorders of pregnancy. Int J Gynaecol Obstet 2004;87:194-8.
30.	Flint AJ. Epidemiology and comorbidity of anxiety disorders in the elderly. Am J Psychiatry 1994;151:640-9.
31.	Hernández-Díaz S, Werler MM, Louik C, Mitchell AA. Risk of gestational hypertension in relation to folic acid supplementation during pregnancy. Am J Epidemiol 2002;156:806-12.
32.	Li Z, Ye R, Zhang L, Li H, Liu J, Ren A. Folic acid supplementation during early pregnancy and the risk of gestational hypertension and preeclampsia. Hypertension 2013;61:873-9.
33.	Timmermans S, Jaddoe VW, Silva LM, Hofman A, Raat H, Steegers-Theunissen RP, et al. Folic acid is positively associated with uteroplacental vascular resistance: The generation R study. Nutr Metab Cardiovasc Dis 2011;21:54-61.
34.	Catov JM, Nohr EA, Bodnar LM, Knudson VK, Olsen SF, Olsen J. Association of periconceptional multivitamin use with reduced risk of preeclampsia among normal-weight women in the Danish national birth cohort. Am J Epidemiol 2009;169:1304-11.
35.	Wen SW, Chen XK, Rodger M, White RR, Yang Q, Smith GN, et al. Folic acid supplementation in early second trimester and the risk of preeclampsia. Am J Obstet Gynecol 2008;198:45.e1-7.
36.	Wang Y, Zhao N, Qiu J, He X, Zhou M, Cui H, et al. Folic acid supplementation and dietary folate intake, and risk of preeclampsia. Eur J Clin Nutr 2015;69:1145-50.

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