Supplementary Material for: External validation of a multivariate model for targeted surfactant replacement

Background and Aim: Early targeted surfactant therapy for preterm infants is recommended but the best criteria to personalize treatment are unclear. We validate a previously published multivariate prognostic model based on gestational age (GA), lung ultrasound score (LUS) and oxygen saturation to inspired oxygen fraction ratio (SatO2/FiO2) using an independent data set. Design: Pragmatic, observational study in 10 Italian and Spanish NICUs, including preterm babies (250 and 336 weeks divided in 3 gestational age intervals) with clinical signs of respiratory distress syndrome and stabilized on CPAP. LUS and SatO2/FiO2 were collected soon after stabilization. Their prognostic accuracy was evaluated on the subsequent surfactant administration by a rigorously masked physician. Results: One hundred seventy-five infants were included in the study. Surfactant was given to 74% infants born at 25 -27 weeks, 38.5% at 28-30 weeks and 26.5% at 31-33 weeks. The calibration curve comparing the validation and the development populations showed significant overlap with an intercept=0.08, 95%C.I. (-0.34; 0.5) and a slope=1.53, 95% C.I. (1.07-1.98). The validation cohort had a high predictive accuracy. Its ROC curve showed an AUC=0.95, 95%C.I. (0.91-0.99) with sensitivity=0.93, 95%C.I. (0.83-0.98), specificity = 0.81, 95% C.I. (0.73-0.88), PPV = 0.76, 95%C.I. (0.65-0.84), NPV=0.95, 95%C.I. (0.88-0.98). LUS≥9 demonstrated the highest sensitivity (0.91, 95%C.I. (0.82-0.97]) and specificity = 0.81, 95%C.I. (0.72-0.88) as individual predictor. LUS and SatO2/FiO2 prognostic performances varied with gestational age. Conclusions: We validated a prognostic model based on LUS and Sat/FiO2 to facilitate early, customized surfactant administration that may improve respiratory management of preterm neonates