External Validation of a Multivariate Model for Targeted Surfactant Replacement

Abstract

<b><i>Introduction:</i></b> 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 inspire oxygen fraction ratio (SatO₂/FiO₂) using an independent data set. <b><i>Methods:</i></b> Pragmatic, observational study in 10 Italian and Spanish NICUs, including preterm babies (25⁰ and 33⁶ weeks divided into 3 GA 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. <b><i>Results:</i></b> 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% CI (−0.34; 0.5) and a slope = 1.53, 95% CI (1.07–1.98). The validation cohort had a high predictive accuracy. Its ROC curve showed an AUC = 0.95, 95% CI (0.91–0.99) with sensitivity = 0.93, 95% CI (0.83–0.98), specificity = 0.81, 95% CI (0.73–0.88), PPV = 0.76, 95% CI (0.65–0.84), NPV = 0.95, 95% CI (0.88–0.98). LUS ≥9 demonstrated the highest sensitivity (0.91, 95% CI [0.82–0.97]) and specificity = 0.81, 95% CI (0.72–0.88) as individual predictor. LUS and SatO₂/FiO₂ prognostic performances varied with GA. <b><i>Conclusion:</i></b> 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.