Supplementation of folic acid in pregnancy and the risk of preeclampsia and gestational hypertension: a meta-analysis

Abstract

ObjectivesWe aimed to systematically assess the relationship between folic acid supplementation in pregnancy and risk of preeclampsia and gestational hypertension.MethodsThe relevant studies were included by retrieving the Embase, PubMed and Cochrane library databases. Data extraction was conducted by two investigators independently. The risk ratio (RR) and 95% confidence interval (CI) were used as effect indexes to evaluate the relationship between folic acid supplementation and risk of gestational hypertension or preeclampsia. A subgroup analysis was performed according to the supplementation patterns of folic acid. The homogeneity of the effect size was tested across the studies, and publication biases were examined.ResultsIn total, 13 cohort studies and 1 randomized controlled trial study was included, containing 160,562 and 149,320 women with and without folic acid supplementation during pregnancy. Pooled results showed that risk of gestational hypertension was not associated with the supplementation of folic acid. However, folic acid supplementation during pregnancy could significantly reduce the risk of preeclampsia. Moreover, the results of subgroup analysis showed that the decreased preeclampsia risk was associated with supplementation of multivitamins containing folic acid rather than folic acid alone.ConclusionsOur findings indicate that the supplementation of multivitamins containing folic acid during pregnancy could significantly lower preeclampsia risk.Electronic supplementary materialThe online version of this article (10.1007/s00404-018-4823-4) contains supplementary material, which is available to authorized users.

Iron-Folate Supplementation during Pregnancy for Prevent Oxidative Stress in Pregnant Rats: Level of MDA, Creatinine, Glucose, Erythrocite, Blood Pressure, Body Weight and Number of Offspring

“…5,8 DNA methylation can play a key role in local control of gene expression. 8 This study also supported by research conducted by Liu, et al 2018 that foud supplementation of multivitamins containing folic acid during pregnancy could ignificantly lower preeclampsia risk. 15 Modification of gene expression can also occur due to changes in regulatory function in histones, especially in the terminal amino groups that are susceptible to changes in posttranslation modification such as methylation, acetylation, phosphorylation and ubiquitination.…”

“…8 This study also supported by research conducted by Liu, et al 2018 that foud supplementation of multivitamins containing folic acid during pregnancy could ignificantly lower preeclampsia risk. 15 Modification of gene expression can also occur due to changes in regulatory function in histones, especially in the terminal amino groups that are susceptible to changes in posttranslation modification such as methylation, acetylation, phosphorylation and ubiquitination. Changes in the methylation pathway that cause a decrease in protein synthesis and methylation of DNA result in abnormalities of vascular smooth muscle proliferation and increase lipid peroxidation.…”

“…Therapy with folic acid administration to reduce Hhcy returns the level of methylation DNA to normal and improves gene expression. 11,15 Alterations to folic acid status could directly impact the amount and patterns of DNA methylation. Specifically, methyl donor nutrients such as methionine, folate, betaine, and choline have been implicated in alterations in methylation patterns.…”

Can Serum Iron Concentrations in Early Healthy Pregnancy Be Risk Marker of Pregnancy-Induced Hypertension?

“…(e.g., multivitamins supplementation in trimester II–III and socioeconomic factors). Some of the causes of iron deficiency mentioned include, the deficiency of folic acid, vitamin B12, and Vitamin A [27,33,34]. Research has shown that deficiencies of iron and vitamins (E, C, D, A, B, and folic acid) can induce inflammations in the placenta [35,36].…”

Nutraceuticals and Hypertensive Disorders in Pregnancy: The Available Clinical Evidence

“…A meta-analysis of 13 cohort studies and one randomized clinical trial, overall involving 309882 pregnant women, showed that supplementation with multivitamins containing folic acid during pregnancy significantly lowers pre-eclampsia risk (RR = 0.69, 95%CI: 0.58; 0.83) but not the risk of gestational hypertension (RR = 1.19, 95%CI: 0.92; 1.54) [26]. However, the Folic Acid Clinical Trial (FACT) recently failed to demonstrate that supplementation with 4 mg/day folic acid beyond the first trimester of gestation prevents pre-eclampsia in women at high risk for this condition (n = 2464; RR = 1.10, 95%CI: 0.90; 1.34) [27].…”