Association of admission C-reactive protein levels and histological chorioamnionitis in patients with preterm premature rupture of membranes: a systematic review and meta-analysis.

Abstract

Background: Preterm premature rupture of membranes (PPROM) is a high-risk obstetric complication. Ascending infection and histological chorioamnionitis (HCA) frequently occur after membrane rupture, contributing to severe adverse maternal and fetal outcomes. Early prediction of HCA using non-invasive biomarkers allows timely clinical management, while the predictive efficacy of C-reactive protein (CRP) for subsequent HCA in PPROM patients remains inconsistent across existing studies. This meta-analysis aimed to systematically evaluate the predictive association.

Methods: We systematically searched PubMed, Scopus, Web of Science and the Cochrane Library from inception to May 20, 2026 for studies on serum CRP and subsequent HCA in PPROM patients. Pooled mean differences (MD) of admission CRP concentrations were calculated using random-effects meta-analysis with results visualized via forest plots. Leave-one-out sensitivity analysis confirmed robustness. Subgroup analyses and meta-regression were applied to explore potential sources of heterogeneity. Funnel plots, combined with Egger's test and Begg's test, were used to evaluate publication bias. All statistical analyses were conducted using R software (version 4.6.0).

Results: Initially, 11 studies were screened. After excluding one low-quality study, 10 studies (1,791 participants) were ultimately included. The pooled results demonstrated that PPROM patients who subsequently developed HCA exhibited higher admission CRP levels than non-HCA controls (MD = 0.439, 95% CI: 0.179-0.700), with substantial heterogeneity (I ² = 87.7%). Meta-regression and subgroup exploration suggested sample size may partially drive cross-study heterogeneity; this moderator accounted for 31.19% of total variance, with a borderline significant association (P = 0.05). Sensitivity analysis confirmed the stability of the pooled estimates. Egger's test revealed no significant publication bias (P > 0.05), but the substantial heterogeneity warrants caution in interpretation.

Conclusion: This meta-analysis suggests that elevated admission CRP levels are modestly correlated with subsequent HCA in PPROM populations. CRP may serve as an auxiliary indicator to assist early risk stratification; however, its clinical utility is limited by the small effect size and substantial heterogeneity across studies. Given the observational design of the included studies, these findings represent association rather than causation. Prospective cohort studies with standardized protocols are needed to confirm these results and assess the incremental value of CRP over existing clinical predictors.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261404654.