Maternal folic acid supplementation for the prevention of preeclampsia: A systematic review and meta-analysis

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#dietary-supplements #evidence-based-medicine #female #folic-acid #humans

Maternal folic acid supplementation for the prevention of preeclampsia: A systematic review and meta-analysis

Bulloch et al., 2018 | Paediatr Perinat Epidemiol | Meta Analysis

Citation

Bulloch Rhodi E, Lovell Amy L, ... Wall Clare R. Maternal folic acid supplementation for the prevention of preeclampsia: A systematic review and meta-analysis. Paediatr Perinat Epidemiol. 2018-Jul;32(4):346-357. doi:10.1111/ppe.12476

Abstract

BACKGROUND: Preeclampsia is a significant contributor to maternal and neonatal morbidity and mortality. Folic acid supplementation is recommended periconceptionally for the prevention of neural tube defects. Epidemiological evidence suggests that maternal folic acid supplementation may play a role in preventing other adverse birth outcomes. This systematic review aimed to investigate the effect of maternal folic acid supplementation during pregnancy on risk of preeclampsia and gestational hypertension. METHODS: Multiple scientific databases and grey literature were searched for relevant studies. Studies were reviewed according to pre-specified inclusion and exclusion criteria. Study characteristics were summarised and study quality was assessed. A meta-analysis of observational studies was conducted to examine the effect of maternal folic acid supplementation on preeclampsia risk. RESULTS: Meta-analysis of eight observational studies showed significantly lower odds of preeclampsia with folic acid supplementation in comparison to no folic acid supplementation: OR = 0.78 (95% CI 0.63, 0.98), with moderately high heterogeneity between studies. Subgroup analysis showed no significant subgroup difference between folic acid supplementation taken by itself, in comparison to folic acid taken in or alongside a multivitamin. CONCLUSION: Low level evidence is available for a modest association between maternal folic acid supplementation and reduction in preeclampsia risk. Future studies should differentiate between early and late onset and mild vs severe preeclampsia, and should control for relevant confounders including the presence of multivitamin supplements. The protocol for this systematic review was prospectively registered with PROSPERO (CRD42015029310).

Key Findings

Meta-analysis of eight observational studies showed significantly lower odds of preeclampsia with folic acid supplementation in comparison to no folic acid supplementation: OR = 0.78 (95% CI 0.63, 0.98), with moderately high heterogeneity between studies. Subgroup analysis showed no significant subgroup difference between folic acid supplementation taken by itself, in comparison to folic acid taken in or alongside a multivitamin.

Outcomes Measured

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Population

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

MeSH Terms

  • Dietary Supplements
  • Evidence-Based Medicine
  • Female
  • Folic Acid
  • Humans
  • Pre-Eclampsia
  • Pregnancy
  • Pregnancy Complications
  • Pregnancy Outcome

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