PROMISE-impact of maternal and neonatal risk factors on the respiratory outcome of extremely preterm infants following PPROM in the second trimester of pregnancy.

Background: Prolonged preterm premature rupture of membranes (PPROM) in the second trimester is associated with heterogeneous neonatal respiratory outcomes, ranging from mild transitional respiratory impairment to dry lung syndrome (DL), pulmonary hypoplasia (PH), bronchopulmonary dysplasia (BPD) and death. Risk assessment is challenging because outcomes are influenced by both gestational maturity and PPROM-specific exposures. This study aimed to evaluate respiratory outcomes after prolonged PPROM using a multifactorial and longitudinal approach that integrates gestational age, amniotic fluid status, inflammatory signs, and maternal characteristics. Methods: We retrospectively analyzed 66 pregnancies with second-trimester PPROM and prolonged latency. Short-term respiratory outcomes were classified as no respiratory disease, dry lung (DL), or pulmonary hypoplasia (PH); neonatal death and BPD were also assessed. Gestational age (GA) at PPROM and at birth were analyzed using ordered groupings with trend testing. Multivariable logistic regression was used to identify independent risk factors. Serial weekly measurements of the single deepest vertical pocket (SDP) were evaluated longitudinally using repeated-measures analysis to compare amniotic fluid trajectories between outcome groups. Results: Respiratory morbidity and death decreased stepwise with increasing GA at PPROM and GA at birth. Lower SDP values were consistently associated with PH, BPD, and death, particularly when median SDP was <2 cm. Longitudinal analysis demonstrated persistently lower SDP values in pregnancies resulting in PH, without evidence of differing SDP trajectories over time between groups. Inflammatory signs were associated with BPD, while maternal age and GA at PPROM were associated with PH and death. DL showed a distinct pattern, with weaker associations to gestational age and amniotic fluid parameters compared with PH. Conclusion: Outcomes after prolonged second-trimester PPROM reflect a multifactorial risk profile in which gestational maturity, amniotic fluid impairment, inflammatory status, and maternal characteristics interact. Integrating longitudinal ultrasound data with gestational-age-based risk stratification can improve counseling and support individualized management strategies in PPROM pregnancies.