External Validation of a Multivariate Model for Targeted Surfactant Replacement

Abstract Introduction: 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. Methods: 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. 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% 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. Conclusion: 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. Key Messages• What is already known on this topic?–Exogenous surfactant administration is a therapeutic keystone for neonatal respiratory distress syndrome. Early individualized surfactant replacement is the preferred strategy, but the criteria for the targeted administration are unclear.• What this study adds?–In the real world, surfactant is often administered beyond the optimal timeframe and not according to official recommendations. We confirm the robustness of a three noninvasive variables model to predict early targeted surfactant administration for a general clinical use.• How this study might affect research, practice, or policy?–Early individualized surfactant administration positively affects