We designed a multicenter randomized trial to compare 3 approaches to the initial respiratory management of preterm neonates: prophylactic surfactant followed by a period of mechanical ventilation (prophylactic surfactant [PS]); prophylactic surfactant with rapid extubation to bubble nasal continuous positive airway pressure (intubate-surfactant-extubate [ISX]) or initial management with bubble continuous positive airway pressure and selective surfactant treatment (nCPAP).


Neonates born at 26

to 29
weeks' gestation were enrolled at participating Vermont Oxford Network centers and randomly assigned to PS, ISX, or nCPAP groups before delivery. Primary outcome was the incidence of death or bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age.


648 infants enrolled at 27 centers. The study was halted before the desired sample size was reached because of declining enrollment. When compared with the PS group, the relative risk of BPD or death was 0.78 (95% confidence interval: 0.59–1.03) for the ISX group and 0.83 (95% confidence interval: 0.64–1.09) for the nCPAP group. There were no statistically significant differences in mortality or other complications of prematurity. In the nCPAP group, 48% were managed without intubation and ventilation, and 54% without surfactant treatment.


Preterm neonates were initially managed with either nCPAP or PS with rapid extubation to nCPAP had similar clinical outcomes to those treated with PS followed by a period of mechanical ventilation. An approach that uses early nCPAP leads to a reduction in the number of infants who are intubated and given surfactant.

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