Meta-analysis of Preterm Premature Rupture of Membranes and Fetal Inflammatory Response Syndrome

Abstract

Objective: To systematically evaluate the impact of fetal inflammatory response syndrome (FIRS) in preterm premature rupture of membranes (PPROM) on neonatal short-term adverse outcomes, and to assess the predictive value of maternal and amniotic fluid inflammatory markers for FIRS. Methods: A systematic search was conducted across PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, and other databases (January 2022–May 2026), including cohort and case-control studies involving PPROM with FIRS. Two reviewers independently screened eligible studies and assessed risk of bias using the NOS scale. Meta-analysis was performed using RevMan 5.4 and Stata 16.0. Results: A total of five high-quality studies (690 cases) were included. Meta-analysis revealed that, compared with the non-FIRS group, infants in the PPROM-FIRS group had significantly higher risks of early-onset sepsis (OR = 4.85, 95% CI: 3.12–7.54), bronchopulmonary dysplasia (OR = 3.42, 95% CI: 2.05–5.88), severe intraventricular hemorrhage (OR = 2.76, 95% CI: 1.67–4.53), necrotizing enterocolitis (OR = 3.35, 95% CI: 1.76–6.38), and respiratory distress syndrome (OR = 2.58, 95% CI: 1.72–3.86) (all P < 0.001). The survival rate of extremely preterm fetuses delivered before 24 weeks’ gestation with FIRS was extremely low. Conclusion: PPROM combined with FIRS significantly increases the risk of multiple short-term adverse neonatal outcomes. Dynamic monitoring of maternal CRP, WBC, and amniotic fluid IL-6 levels may help identify FIRS early, providing evidence for decisions regarding antenatal corticosteroids or termination of pregnancy, thereby improving perinatal outcomes.