Objective: To assess the impact of beractant treatment using the less invasive surfactant administration (LISA) technique on perinatal outcomes in a prospective cohort of preterm infants with respiratory distress syndrome (RDS).Design: Single-center prospective study conducted in a Department of Neonatology of a tertiary care university-affiliated hospital in Madrid, Spain.Methods: Preterm infants born at <31 + 6 weeks' gestation attended in the neonatal intensive care unit (NICU) between 2012 and 2016. The main outcome was the need of invasive mechanical ventilation during the first 3 days of life. Beractant (100 mg; 4 mL/kg) was administered using the intubation-surfactant-extubation (INSURE) method during 2012 and 2013, and using the LISA procedure between 2014 and 2016.Results: The study population included 512 infants, 232 in the first period and 280 in the second period. Mechanical ventilation exposure during hospitalization showed a significant reduction in the second study period, with an adjusted OR of 0.61, 95% CI 0.39-0.96. Also, an increase of free-bronchopulmonary dysplasia (BPD) survival was found (adjusted OR 2.14, 95% CI 1.29-3.55). These significant differences in perinatal outcomes were observed only in the group of infants of 26 + 0 to 28 + 6 gestational weeks. The success rate of the first dose of beractant using LISA regarding no need of intubation during the first 3 days of life was 54% increasing to 69% in the group of 26 + 0-28 + 6 weeks of gestation. The success rate regarding free-BPD survival was 63.5% in the whole series of LISA treated patients and 72.4% in the group of 26 + 0-28 + 6 weeks. Oxygen reduction after surfactant administration (OR 39.6, 95% CI 6.1-255.8, p < .001) was predictor of LISA success, whereas LISA failure was an independent factor for air leak (OR 18.92, 95% CI 1.31-272.32, p = .031) and Death or BPD outcome (OR 19.3, 95% IC 2.5-147.4, p = .004). Gestational age was inversely associated with the need of intubation after LISA (OR 0.53, 95% CI 0.32-0.87, p = .013).Conclusions: Beractant administration by LISA technique effective reduced the need of intubation during the first 3 days of life and was associated with an increase in survival-free BPD in the group of infants born at 26 + 0 and 28 + 6 weeks' gestation.

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