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

© 2026 by the Authors. Licensee Whioce Publishing, Singapore. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

Download PDF

Cite

XML

HTML

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.

References

Liu S, Zhao Y, Li X, et al., 2023, Expression and Clinical Significance of the Toll-Like Receptor 4/Myeloid Differentiation Factor/Nuclear Factor-κB Pathway in Placentas of Women with Preterm Premature Rupture of Membranes. Chinese Journal of Infection and Chemotherapy, 23(1): 40–46.

Wu F, Cai Y, Hua S, 2025, Analysis of Obstetric Factors Contributing to Adverse Outcomes in Preterm Infants Born to Women with Preterm Premature Rupture of Membranes. Journal of Practical Obstetrics and Gynecology, 41(8): 666–671.

Liu D, Li H, Feng M, et al., 2024, Fetal Inflammatory Response Syndrome and Pulmonary Disease in Preterm Infants. Chinese Journal of Practical Pediatrics, 39(9): 718–720.

Firsova AB, Salas SM, Kuemmerle LB, et al., 2025, Spatial Single-Cell Atlas Reveals Regional Variations in Healthy and Diseased Human Lung. Nature Communications, 16(1): 89.

Jain A, Aggarwal R, Gupta N, Mehndiratta M, Gogoi P, Batra P, Agarwal R, 2022, Reduced Fetal Urine Production Rate—An Early Marker of Fetal Inflammatory Response Syndrome in Preterm Premature Rupture of Membranes: Prospective Cohort Study. International Journal of Gynecology & Obstetrics, 159(2): 444–450.

Grill A, Mikula F, Jansen S, Klein L, Rittenschober-Boehm J, Leitich H, Farr A, Berger A, Goeral K, 2025, Neonatal Outcomes Following Previable Rupture of Membranes Below 23 Weeks’ Gestation. European Journal of Pediatrics, 184(8): 503.

Galletta MAK, Schultz R, Sartorelli MFGOP, Guerra ECL, Agra IKR, Peres SV, Francisco RPV, 2023, Clinical Characteristics, Complications, and Predictive Model of Histological Chorioamnionitis in Women with Preterm Premature Rupture of Membranes. PLoS One, 18(4): e0283974.

Cossart A, Storme L, Ghesquiere L, Houfflin-Debarge V, Le Duc K, Boukhris MR, 2026, Previable Preterm Premature Rupture of Membranes (Before 24 Weeks Gestation): Pregnancy and Neonatal Outcomes. European Journal of Pediatrics, 185(2): 113.

Seravalli V, Colucci C, Di Cencio C, Morucchio A, Barsanti F, Di Tommaso M, 2025, Latency to Delivery and Incidence of Adverse Obstetric and Perinatal Outcomes in Preterm Premature Rupture of Membranes Before 32 Weeks. Archives of Gynecology and Obstetrics, 311(6): 1569–1577.

Zhang L, Zhao J, Xu Y, et al., 2023, Predictive Value of Cervical-Vaginal Fluid IL-6, IL-10, and IL-19 for Fetal Inflammatory Response Syndrome Secondary to Preterm Premature Rupture of Membranes. Western Medicine, 35(5): 724–728 + 734.

Su Y, Wang Q, Gao Y, 2025, Relationship Between the Duration of Mechanical Ventilation and Improvement in Respiratory Function and the Risk of Bronchopulmonary Dysplasia in Newborns with Respiratory Distress Syndrome. Journal of Environment and Health, 42(4): 300–306.

Previous article in this issue

Next article in this issue