A Predictive Model for Moderate or Severe Neonatal Acute Respiratory Distress Syndrome in Extremely Preterm Infants with Premature Rupture of Membranes: Development and Internal Validation

Purpose: Preterm premature rupture of membranes (PROM) is a major cause of extremely preterm birth. Intrauterine infection and inflammation markedly increase the risk of neonatal acute respiratory distress syndrome (NARDS), particularly moderate or severe cases associated with poor outcomes. This study developed and validated a prediction model for moderate or severe NARDS in this population using inflammatory biomarkers. Patients and Methods: This single center retrospective cohort study included 243 extremely preterm infants with PROM from 2015 to 2024. The primary outcome was moderate or severe NARDS occurring within 72 hours after delivery, diagnosed according to Montreux criteria. Patients were grouped by NARDS severity. Predictive variables were screened using LASSO regression and incorporated into a multivariable logistic model to build a nomogram. Model performance was assessed through receiver operating characteristic curves (ROC), calibration plots and decision curve analysis (DCA). Results: The primary outcome incidence was 20.2% (49/243). Multivariable analysis identified elevated C-reactive protein (CRP) (OR=1.04, 95% CI:1.01– 1.07), decreased platelet count (OR=0.99, 95% CI:0.988– 0.998), decreased albumin (OR=0.87, 95% CI:0.80– 0.95), and decreased arterial pH (OR=0.01, 95% CI:0.001– 0.041) as independent predictors. The nomogram integrating these four parameters demonstrated excellent discrimination with an area under the curve (AUC) of 0.824. Internal validation demonstrated good robustness (C-index=0.795). To enhance clinical translation, we developed an interactive web calculator for real time risk assessment to guide pediatricians’ clinical decision making. DCA established a 30% risk threshold to inform early interventions. Conclusion: The validated model containing CRP, platelets, albumin and pH effectively identifies high risk PROM infants. The web based interface enables practical bedside application for early detection of critical cases. Patients with predicted probabilities reaching 30% should be considered for preventive lung protection measures. Additional multicenter studies are needed to verify wider applicability and enhance clinical implementation protocols. Keywords: acute respiratory distress syndrome, extremely preterm infants, premature rupture of membranes, nomogram, biological markers