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Importance: Surfactant administration may be needed in late preterm through full-term neonates, but the pathophysiology of their respiratory failure can be different from that of early preterm neonates. The lung ultrasonography score (LUS) is accurate to guide surfactant replacement in early preterm neonates, but to our knowledge, it has not yet been studied in the late preterm through full-term neonatal population., Objective: To assess whether LUS is equally accurate to predict surfactant need in late preterm through full-term neonates as in early preterm neonates., Design, Setting, and Participants: This prospective, international, multicenter diagnostic study was performed between December 2022 and November 2023 in tertiary academic neonatal intensive care units in France, Italy, Spain, and the US. Late preterm through full-term neonates (≥34 weeks' gestation) with respiratory failure early after birth were enrolled., Exposure: Point-of-care lung ultrasonography to calculate the neonatal LUS (range, 0-18, with higher scores indicating worse aeration), which was registered in dedicated research databases and unavailable for clinical decision-making., Main Outcomes and Measures: The main outcomes were the area under the curve (AUC) in receiver operating characteristic analysis and derived accuracy variables, considering LUS as a replacement for other tests (ie, highest global accuracy) and as a triage test (ie, highest sensitivity). Sample size was calculated to assess noninferiority of LUS to predict surfactant need in the study population compared with neonates born more prematurely. Correlations of LUS with the ratio of hemoglobin oxygen saturation as measured by pulse oximetry (SpO2) to fraction of inspired oxygen (FiO2) and with the oxygen saturation index (OSI) were assessed., Results: A total of 157 neonates (96 [61.1%] male) were enrolled and underwent lung ultrasonography at a median of 3 hours (IQR, 2-7 hours) of life; 32 (20.4%) needed surfactant administration (pretest probability, 20%). The AUC was 0.87 (95% CI, 0.81-0.92). The highest global accuracy and sensitivity were reached for LUS values higher than 8 or 4 or lower, respectively. Subgroup analysis gave similar diagnostic accuracy in neonates born late preterm (AUC, 0.89; 95% CI, 0.81-0.97; n = 111) and early term and later (AUC, 0.84; 95% CI, 0.73-0.96; n = 46). After adjusting for gestational age, LUS was significantly correlated with SpO2:FiO2 (adjusted β, -10.4; 95% CI, -14.0 to -6.7; P < .001) and OSI (adjusted β, 0.2; 95% CI, 0.1-0.3; P < .001)., Conclusions and Relevance: In this diagnostic study of late preterm through full-term neonates with respiratory failure early after birth, LUS accuracy to predict surfactant need was not inferior to that observed in earlier preterm neonates. An LUS higher than 8 was associated with highest global accuracy (replacement test), suggesting that it can be used to guide surfactant administration. An LUS value of 4 or lower was associated with the highest sensitivity (triage test), suggesting it is unlikely for this population to need surfactant.

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., (© 2023 S. Karger AG, Basel.)

Background: Chorioamnionitis is associated with preterm delivery and morbidities; its role in lung disease is controversial. The aim of this study is to assess the effect of chorioamnionitis on metabolite and lipid profiles of epithelial lining fluid in preterm newborns with respiratory distress syndrome (RDS)., Methods: The study involved 30 newborns with RDS, born from mothers with or without histological chorioamnionitis (HCA): HCA+, N = 10; HCA-, N = 20. Patients had a gestational age ≤30 weeks; the groups were matched for age and birth weights. Tracheal aspirates were collected within 24 h after birth and analyzed using liquid chromatography/mass spectrometry-based untargeted lipidomics., Results: According to Mann-Whitney U tests, 570 metabolite features had statistically significantly higher or lower concentrations (p < 0.05) in tracheal aspirates of HCA+ compared to HCA-, and 241 metabolite features were putatively annotated and classified. The most relevant changes involved higher levels of glycerophospholipids (fold change 2.42-17.69) and sphingolipids, with lower concentration of all annotated sphingomyelins in HCA+ (fold change 0.01-0.50)., Conclusions: Untargeted lipidomics of tracheal aspirates suggested the production of lipid mediators in the context of an ongoing inflammatory status in HCA+ babies. However, the effect of chorioamnionitis on epithelial lining fluid composition deserves further investigations on a larger group of infants., Impact: Our lipidomics investigation on tracheal aspirates of preterm newborns at birth suggested that exposure to maternal histological chorioamnionitis may cause changes in epithelial lining fluid composition. This is the first description of epithelial lining fluid lipidomic profiles in preterm infants with and without exposition to chorioamnionitis. These results could provide novel link between placental membrane inflammation and newborns' respiratory outcome., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objectives: To compare the efficacy of intra-tracheal (IT) surfactant/budesonide (SB) with that of surfactant alone (S) in reducing the rate of bronchopulmonary dysplasia (BPD) at 36 weeks post-menstrual age (PMA), we included extremely preterm very low birth weight (VLBW) infants with severe respiratory distress syndrome (RDS) in our tertiary neonatal level of care unit (Padua, Italy)., Study Design: A retrospective chart review of two cohorts of extremely preterm VLBW neonates (<28 +0  gestation weeks, birth weight [BW] < 1500 g) born in two consequent epochs (2017-2018/2018-2019) were compared. The SB group received surfactant (200 mg/kg 1st dose) and budesonide (0.25 mg/kg), while the S group received surfactant alone., Results: Among 68 neonates with RDS Grades III-IV, FiO 2  ≥ 0.3 within 12 h of life, 18 were included in each group after matching for perinatal, clinical, and laboratory characteristics. IT SB did not affect the rate of BPD (Vermont Oxford Network, Jensen's, and National Institute of Child Health and Human Development BPD Workshop 2018 definitions), death, BPD, or death at 36 weeks PMA. Hypotension requiring inotropic support within the first 5 days was lower in those receiving the combined treatment (p = .03). The SB group had fewer admissions to pediatric ward due to respiratory causes up to 12 months of corrected age (p = .03)., Conclusion: The preliminary results of this retrospective study suggest that in extremely preterm VLBW infants, IT SB for severe RDS did not affect the incidence of BPD, death, and BPD or death at 36 weeks PMA, compared to surfactant alone. The combined therapy proved to be safe in this population. Further studies are warranted to explore the role of early IT steroids on respiratory morbidity in preterm infants., (© 2021 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)