Obstet Gynecol Sci.  2016 Mar;59(2):110-115. 10.5468/ogs.2016.59.2.110.

Folic acid alone or multivitamin containing folic acid intake during pregnancy and the risk of gestational hypertension and preeclampsia through meta-analyses

  • 1Department of Obstetrics and Gynecology, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea. drsook@schmc.ac.kr


The objective of this study was to assess the effect of folic acid and multivitamin use during pregnancy on the risk of developing of hypertensive disorder of pregnancy.
Two reviewers independently determined all prospective cohort study, retrospective cohort study, large population based cohort study, retrospective secondary analysis, and double blinded, placebo-controlled, randomized clinical trial published using PubMed Medline database, KERIS (Korea Education and Research Information Service), Scopus, and the Cochrane Central Register of controlled trials comparing before conception throughout pregnancy intake oral multivitamin containing folic acid or folic acid alone. Meta-analyses were estimated with odds ratios and 95% confidence intervals (CIs) using random effect analysis according to heterogeneity of studies.
Data from six effect sizes from six studies involving 201,661 patients were enrolled. These meta-analyses showed multivitamin containing folic acid or folic acid alone was not significantly effective in reducing gestational hypertension or preeclampsia incidence (odds ratio, 0.91; 95% CI, 0.81 to 1.03) than the placebo. And the difference of effective sizes of preeclampsia and gestational hypertension according to two dependent variables, multivitamin and folic acid were not significant, respectively (point estimate, 0.66; 95% CI, 0.46 to 0.96).
These meta-analyses demonstrate multivitamin containing folic acid or folic acid alone was not significantly effective in reducing gestational hypertension or preeclampsia incidence.


Folic acid; Hypertension, pregnancy-induced; Meta-analysis; Multivitamin; Pre-eclampsia

MeSH Terms

Cohort Studies
Folic Acid*
Hypertension, Pregnancy-Induced*
Odds Ratio
Population Characteristics
Prospective Studies
Retrospective Studies
Folic Acid


  • Fig. 1 Flow of information through different phases of review.

  • Fig. 2 Funnel plot for assessing publication bias.


1. Leeman L, Fontaine P. Hypertensive disorders of pregnancy. Am Fam Physician. 2008; 78:93–100.
2. Cifkova R. Why is the treatment of hypertension in pregnancy still so difficult? Expert Rev Cardiovasc Ther. 2011; 9:647–649.
3. Sibai BM. Diagnosis and management of gestational hypertension and preeclampsia. Obstet Gynecol. 2003; 102:181–192.
4. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol. 2000; 183:S1–S22.
5. Yanez P, Vasquez CJ, Rodas L, Duran A, Chedraui P, Liem KH, et al. Erythrocyte folate content and serum folic acid and homocysteine levels in preeclamptic primigravidae teenagers living at high altitude. Arch Gynecol Obstet. 2013; 288:1011–1015.
6. Tang Z, Buhimschi IA, Buhimschi CS, Tadesse S, Norwitz E, Niven-Fairchild T, et al. Decreased levels of folate receptor-β and reduced numbers of fetal macrophages (Hofbauer cells) in placentas from pregnancies with severe pre-eclampsia. Am J Reprod Immunol. 2013; 70:104–115.
7. 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; 26:257–260.
8. 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.e1–45.e7.
9. Bodnar LM, Tang G, Ness RB, Harger G, Roberts JM. Periconceptional multivitamin use reduces the risk of preeclampsia. Am J Epidemiol. 2006; 164:470–477.
10. Hernandez-Diaz S, Werler MM, Louik C, Mitchell AA. Risk of gestational hypertension in relation to folic acid supplementation during pregnancy. Am J Epidemiol. 2002; 156:806–812.
11. 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; 61:873–879.
12. Ray JG, Mamdani MM. Association between folic acid food fortification and hypertension or preeclampsia in pregnancy. Arch Intern Med. 2002; 162:1776–1777.
13. Theriault S, Giguere Y, Masse J, Lavoie SB, Girouard J, Bujold E, et al. Absence of association between serum folate and preeclampsia in women exposed to food fortification. Obstet Gynecol. 2013; 122(2 Pt 1):345–351.
14. Kim MW, Ahn KH, Ryu KJ, Hong SC, Lee JS, Nava-Ocampo AA, et al. Preventive effects of folic acid supplementation on adverse maternal and fetal outcomes. PLoS One. 2014; 9:e97273.
15. 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; 135:1776–1781.
16. Talaulikar VS, Arulkumaran S. Folic acid in obstetric practice: a review. Obstet Gynecol Surv. 2011; 66:240–247.
17. Osterhues A, Ali NS, Michels KB. The role of folic acid fortification in neural tube defects: a review. Crit Rev Food Sci Nutr. 2013; 53:1180–1190.
18. Gui S, Jia J, Niu X, Bai Y, Zou H, Deng J, et al. Arginine supplementation for improving maternal and neonatal outcomes in hypertensive disorder of pregnancy: a systematic review. J Renin Angiotensin Aldosterone Syst. 2014; 15:88–96.
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