External Validation of a Multivariate Model for Targeted Surfactant Replacement
Francesco Raimondi, Pasquale Dolce, Claudio Veropalumbo, Enrico Sierchio, Rebeca Gregorio‐Hernández, Javier Rodríguez Fanjul, Fabio Meneghin, Roberto Raschetti, Luca Bonadies, Iuri Corsini, Almudena Alonso‐Ojembarrena, Serena Salomè, Lorena Rodeño Fernández, Manuel Sánchez Luna, Gianluca Lista, Fabio Mosca, Carlo Dani, Eugenio Baraldi, Lucio Giordano, Peter G. Davis, Letizia Capasso
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 (SatO<sub>2</sub>/FiO<sub>2</sub>) using an independent data set. <b><i>Methods:</i></b> Pragmatic, observational study in 10 Italian and Spanish NICUs, including preterm babies (25<sup>0</sup> and 33<sup>6</sup> weeks divided into 3 GA intervals) with clinical signs of respiratory distress syndrome and stabilized on CPAP. LUS and SatO<sub>2</sub>/FiO<sub>2</sub> 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 SatO<sub>2</sub>/FiO<sub>2</sub> prognostic performances varied with GA. <b><i>Conclusion:</i></b> We validated a prognostic model based on LUS and Sat/FiO<sub>2</sub> to facilitate early, customized surfactant administration that may improve respiratory management of preterm neonates.