Abstract:Objective To construct and validate a model for predicting the prognosis of neonatal respiratory distress syndrome (NRDS) in premature infants based on lung ultrasound score, serum syndecan-1 (SDC-1), and angiopoietin-like protein 4 (ANGPTL4).Methods The clinical data of 350 premature infants with NRDS admitted to Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine in Hebei Province from July 2022 to June 2025 were retrospectively analyzed. Using a random number table, the infants were divided into a modeling set (n = 245) and a validation set (n = 105) at a ratio of 7:3. According to outcomes in the modeling set, the infants were further divided into a favorable prognosis group (n = 131) and an unfavorable prognosis group (n = 114). General data, 1-min and 5-min Apgar scores, Score for Neonatal Acute Physiology with Perinatal Extension II (SNAPPE II), lung ultrasound score, white blood cell count, platelet count, interleukin-6 (IL-6), procalcitonin (PCT), SDC-1, and ANGPTL4 levels were compared. Multivariate stepwise logistic regression was used to analyze factors associated with an unfavorable prognosis in premature infants with NRDS. A prediction model was constructed and internally validated using bootstrap resampling (n = 1,000). The Hosmer-Lemeshow test was used to assess model goodness of fit, with P > 0.05 indicating good fit. ROC, calibration, and decision curves were used to evaluate model performance.Results General data did not differ significantly between the modeling and validation sets (P > 0.05). The proportion of early preterm birth, SNAPPE II score, ventilation duration, lung ultrasound score, and SDC-1 and ANGPTL4 levels were higher, whereas birth weight and 1-min and 5-min Apgar scores were lower, in the unfavorable prognosis group than in the favorable prognosis group (P < 0.05). Early preterm birth (< 32 weeks), higher SNAPPE II score, lung ultrasound score, SDC-1 level, and ANGPTL4 level were independent risk factors for an unfavorable prognosis, whereas a higher 1-min Apgar score was an independent protective factor (P < 0.05). Based on the regression analysis, a model for predicting an unfavorable prognosis in premature infants with NRDS was established. The areas under the curve for the modeling and validation sets were 0.815 (95% CI: 0.761, 0.862) and 0.800 (95% CI: 0.711, 0.872), respectively. The Hosmer-Lemeshow goodness-of-fit test was nonsignificant in both sets (P > 0.05). At threshold probabilities of 0.05-0.95, the model-based strategy provided greater net benefit than the treat-all and treat-none strategies in both sets, with a particularly marked advantage at thresholds of 0.10-0.80.Conclusion The model based on lung ultrasound score, serum SDC-1, and ANGPTL4 has good discrimination and high agreement with actual outcomes and may provide a reference for clinical decision-making in premature infants with NRDS.