Early onset sepsis (EOS) is a potentially fatal condition in neonates, and its correct management is still challenging for neonatologists. Early antibiotic administration in the neonatal period may carry short- and long-term risks. Neonatal EOS calculator has been recently introduced as a new strategy to manage infants at risk of sepsis, and has shown promising results. Methods: In this single-center observational retrospective study, 1000 neonates ≥ 34 weeks’ gestation were enrolled with the aim to evaluate our standard protocol for the management of suspected EOS compared to the EOS calculator. Outcome measures included the following: (1) incidence of EOS and (2) proportion of infants in need of sepsis evaluations and antibiotics using our standard protocol versus theoretical application of EOS calculator. Results: A total of 223/1000 infants underwent blood investigations versus 35/1000 (3.5%) if EOS calculator had been applied (p < 0.0001; k = 0.18). Furthermore, 48/1000 infants received antibiotics with our protocol versus 35/1000 with EOS calculator (p = 0.12; k = 0.58). Three infants had a positive blood culture that EOS calculator would have missed. Conclusions: In our study, EOS calculator could have reduced investigations but not antibiotic therapy. EOS calculator is an effective and promising tool, but further studies are required to improve it.

Background: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. Methods: In this study, 382 infants born at 24⁺⁰–27⁺⁶ weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24⁺⁰ to 25⁺⁶ weeks or 26⁺⁰ to 27⁺⁶ weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). Discussion: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24⁺⁰–27⁺⁶ weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life. Trial registration: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Background: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). Goals of different methods of surfactant administration are to reduce duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD), however the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. Methods: In this study 382 infants born at 24⁺⁰-27⁺⁶ weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. Secondary outcomes are: BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular haemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include centre and gestational age (24⁺⁰ to 25⁺⁶ weeks or 26⁺⁰ to 27⁺⁶ weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). Discussion: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24⁺⁰-27⁺⁶ weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 hours of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life. Trial registration: ClinicalTrials.gov identifier NCT05711966