Time-Threshold Dose-Response Relationship Between Duration of Premature Rupture of Membranes and Maternal, Neonatal, and Laboratory Evidence of Infection: A Systematic Review and Meta-Analysis.
Year: 2026
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: Objective: To identify the continuous dose-response relationship between the duration of premature rupture of membranes (PROM) and the probability of neonatal and maternal infectious morbidity. Methods: This meta-analysis and systematic review synthesise data from 15 studies worldwide involving more than 70,000 mother-neonate pairs. A two-step random-effects model of PROM duration as a continuous dose, using restricted cubic splines, was used to estimate specific risk thresholds. Results: The analysis established a progressive, non-linear escalation of risk. The onset of statistical risks at 16 hours is the early-onset pneumonia (Adjusted OR 1.86, 95% CI: 1.152.99). At the age of 18 hours, the incidence of culture-proven sepsis in neonates was 4.0%, and the odds ratio for maternal fever was significantly higher (AOR 36.6). The analysis of the ROC curves revealed a critical mathematical pivot point at 37 hours, after which complications escalate exponentially. Latency greater than 48 hours was the most significant independent predictor of culture-proven sepsis, with an increased risk of 8.2 (p < 0.001). Histologic chorioamnionitis was detected in 39% of mothers, and in many cases, they are clinically silent. Considerable heterogeneity (I2 > 60%) was mainly caused by gestational age disparities in cohorts of extremely preterm and term babies. Conclusion: PROM latency risk is not a threat but accelerates with time. Although 18 hours will be an acceptable early warning level, the range of 37 to 48 hours is a high-risk period that needs aggressive treatment. International guidelines need to be reviewed to reflect this non-linear trend, especially regarding pregnancy, where the risks of delivery are low compared to the rising risk of latency.
Source: La Clinica Terapeutica
DOI: 10.7417/ct.2026.2052
Authors: Iman Shawky Hassan, Aziza Hussein Nassef, Mariam Salah Mohamed Emam, Mohammad Abd Elhameed Alwaseef, Kareem Salah Eldin Fekry Madbouly, Narmen Hamadelnil Ibrahim Eltrafi, Naglaa Fathi Mohammed Agaba, Shaimaa Ali Barakat, Asmaa R Ali, Amal Mahmoud Abd El Ghany Othman, Mai Nabil Ageez, Abdulmabod Omar, Rana Mahmoud Youssef Mohamed Breika, Doaa Helmy Abd Elkader Yousef, Rania Fakhry Abdulrazek Okasha, Nawal S Gouda, Eman Hashish, Doaa Fouad Ali, Hanan Shehata Mohamed, Rehab Mohamed Ateya, Haidy Mahmoud Nasr, Hanan A Hegazy, Abd Elhalim Mohamed Abd Elhalim, Hala S M Abdelmotogaly, Ramy Saleh Abdelghany
Institutions: National Research Centre, Al-Azhar University, Jahra Hospital, Ministry of Health, Ministry of Health and Population, Tanta University, York Hospital, York Teaching Hospital NHS Foundation Trust, Northern Border University, Mansoura University, Alexandria University, Ain Shams University, Zagazig University, New Valley University, Armed Forces College of Medicine
Language: English
Subfield: History
Field: Arts and Humanities
Domain: Social Sciences
Open Access status: diamond
OpenAlex ID: W7120344265