Evaluation of Maternal Inflammatory Biomarkers in Preterm Prelabor Rupture of Membranes: A Systematic Review and...

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.