The Association Between the Risk of Hypertensive Disorders of Pregnancy and Folic Acid: A Systematic Review and Meta-Analysis

Yu et al., 2021 | J Pharm Pharm Sci | Meta Analysis

Citation

Yu Yahui, Sun Ximu, ... Feng Xin. The Association Between the Risk of Hypertensive Disorders of Pregnancy and Folic Acid: A Systematic Review and Meta-Analysis. J Pharm Pharm Sci. 2021;24:174-190. doi:10.18433/jpps31500

Abstract

PURPOSE: Although folic acid (FA) supplementation has been shown to reduce general cardiovascular risks, its impact on hypertensive disorders of pregnancy (HDP) is unclear. We performed a systematic review and meta-analysis to clarify the association between FA and the risk of HDP (pre-eclampsia (PE) and gestational hypertension (GH)). METHODS: PubMed, EmBase, and Cochrane Library were searched up to June 18, 2020, stratified by type of disease, initiation time of FA, form of FA and pre-conception Body Mass Index (BMI). The quality assessment of included studies was evaluated using Newcastle-Ottawa Scale (NOS) for cohort studies and Cochrane Collaboration's Risk of Bias Assessment Tool for randomized controlled trials (RCTs). Between-study heterogeneity was quantified using Cochran's Q-statistic and I2 statistics. Sensitivity analysis was performed by excluding the studies one by one, and publication bias was analyzed using funnel plots. RESULTS: Twenty studies with 359041 patients were identified for inclusion in the meta-analysis which included 3 RCTs and 17 cohort studies. Pooled estimates showed RR of 0.83 (95%CI 0.74-0.93, P=0.0008) for association between low dose FA (LD-FA) and the risk of PE, but LD-FA was not associated with GH (RR 1.05, 95% CI 0.97-1.13, P=0.20). In addition, the results of subgroup analysis showed that post-conception LD-FA had a 31% decreased risk of PE (RR 0.69, 95% CI 0.59-0.80, P<0.00001), and LD-FA in patients with pre-conception BMI<25 kg/m2 had a 32% decreased risk of PE (RR 0.68, 95% CI 0.56-0.81, P<0.0001) Conclusions: LD-FA significantly decreased the risk of PE but not GH, and post-conception LD-FA and pre-conception BMI<25 kg/m2 were considered as protective factors to reduce the risk of PE.

Key Findings

Twenty studies with 359041 patients were identified for inclusion in the meta-analysis which included 3 RCTs and 17 cohort studies. Pooled estimates showed RR of 0.83 (95%CI 0.74-0.93, P=0.0008) for association between low dose FA (LD-FA) and the risk of PE, but LD-FA was not associated with GH (RR 1.05, 95% CI 0.97-1.13, P=0.20). In addition, the results of subgroup analysis showed that post-conception LD-FA had a 31% decreased risk of PE (RR 0.69, 95% CI 0.59-0.80, P<0.00001), and LD-FA in pat

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population pre
Sample Size 359041
Age Range See abstract
Condition hypertension

MeSH Terms

  • Cohort Studies
  • Female
  • Folic Acid
  • Humans
  • Hypertension, Pregnancy-Induced
  • Pregnancy
  • Randomized Controlled Trials as Topic
  • Risk

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis, Systematic Review
  • Vertical: folate

Provenance


Source extracted via PubMed E-utilities API on 2026-04-09