Objective To compare the effectiveness of nasal continuous positive airway pressure (NCPAP) and nasal intermittent positive-pressure ventilation (NIPPV) as the initial respiratory support within the minimally invasive surfactant therapy (MIST) approach in preterm infants with respiratory distress syndrome.

Design Prospective, randomised controlled study.

Setting Tertiary neonatal intensive care unit.

Patients and interventions This study enrolled 200 preterm infants with a gestational age of 26–32 weeks who showed signs of respiratory distress but did not require intubation in the delivery room. Surfactant therapy was performed using the MIST approach in the patients who met the criteria for surfactant administration.

Main outcome measures The primary outcomes were a need for intubation within the first 72 h of life and a surfactant requirement.

Results The infants in the study displayed similar characteristics at birth. Fewer infants in the NIPPV group required surfactant therapy (38% vs 60%; p=0.002) or invasive ventilation during the first 72 h of life (13% vs 29%; p=0.005), and NIPPV reduced the rate of moderate-to-severe bronchopulmonary dysplasia (BPD) (7% vs 16%; p=0.046). Multivariate logistic regression analysis showed that NIPPV support (OR: 0.36, 95% CI 0.17 to 0.76; p=0.008) and higher gestational age (OR: 0.76, 95% CI 0.59 to 0.98; p=0.041) reduced the need for invasive ventilation within the first 72 h of life. Surfactant requirement was also decreased with NIPPV support (OR: 0.39, 95% CI 0.22 to 0.71; p=0.002). However, there was no impact on BPD, based on the multivariate analysis.

Conclusions In infants born at 26–32 weeks’ gestation, NIPPV reduced the need for invasive ventilation and the surfactant requirement within the MIST approach.

Trial registration number ClinicalTrials.gov under identifier NCT01741129.