# Evaluation of Maternal Inflammatory Biomarkers in Preterm Prelabor Rupture of Membranes: A Systematic Review and Meta-Analysis

**Authors:** Sandra Ioana Neamțu, Mihai Sava, Alina Simona Bereanu, Raluca Maria Bădilă, Ioana Roxana Codru, Bogdan Ioan Vintilă, Simina Mustățea, Oana Stoia, Radu Chicea

PMC · DOI: 10.3390/medicina62010020 · Medicina · 2025-12-22

## TL;DR

This study finds that high levels of the inflammatory biomarker IL-6 in mothers are strongly linked to preterm rupture of membranes, suggesting it could help identify high-risk pregnancies.

## Contribution

The study identifies IL-6 as a superior biomarker for predicting preterm prelabor rupture of membranes compared to other inflammatory markers.

## Key findings

- Maternal IL-6 concentrations were significantly elevated in PPROM cases compared to controls in both serum and amniotic fluid.
- IL-6 showed stronger diagnostic and prognostic value than CRP, IL-8, and TNF-α in PPROM.
- Elevated IL-6 is associated with adverse perinatal outcomes in pregnancies with PPROM.

## Abstract

Background and Objectives: Preterm prelabor rupture of membranes (PPROM) is a significant obstetric complication associated with increased maternal and neonatal morbidity and mortality. Inflammation plays a central role in its pathophysiology, and maternal inflammatory biomarkers have gained increasing attention as potential predictors of disease onset and adverse outcomes. Materials and Methods: This systematic review and meta-analysis synthesized evidence from PubMed, Scopus and Web of Science databases evaluating maternal inflammatory biomarkers—particularly interleukin-6 (IL-6)—in women with PPROM compared with controls. Eligible studies assessed biomarker levels in serum, plasma, or amniotic fluid and reported quantitative outcomes. Data were pooled using random-effects models, and heterogeneity was quantified using the I2 statistic. Results: A total of 23 studies involving 2841 participants were included. Maternal IL-6 concentrations were significantly elevated in PPROM compared with controls in both maternal serum (pooled SMD = 1.72; 95% CI: 1.15–2.29; p < 0.001) and amniotic fluid (SMD = 2.84; 95% CI: 2.01–3.67; p < 0.001). CRP showed a moderate association (SMD = 0.98; 95% CI: 0.61–1.36; p < 0.001), whereas IL-8 and TNF-α displayed inconsistent relationships. Conclusions: Elevated maternal IL-6 concentrations, particularly in amniotic fluid, are strongly associated with PPROM and adverse perinatal outcomes. IL-6 demonstrated superior diagnostic and prognostic value compared with other inflammatory markers. These findings support IL-6 as a promising biomarker for early risk identification and individualized the management of high-risk pregnancies.

## Linked entities

- **Proteins:** IL6 (interleukin 6), CRP (C-reactive protein), CXCL8 (C-X-C motif chemokine ligand 8), TNF (tumor necrosis factor)
- **Diseases:** PPROM (MONDO:0012511)

## Full-text entities

- **Genes:** CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}
- **Diseases:** Inflammation (MESH:D007249), PPROM (MESH:C563032), Prelabor Rupture of Membranes (MESH:D005322), obstetric complication (MESH:D007744)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

35 references — full list in the complete paper: https://tomesphere.com/paper/PMC12842887/full.md

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Source: https://tomesphere.com/paper/PMC12842887