To assess the efficacy and safety of early, noninvasive inhaled nitric oxide (iNO) therapy in premature newborns who do not require mechanical ventilation.

We performed a multicenter randomized trial including 124 premature newborns who required noninvasive supplemental oxygen within the first 72 hours after birth. Newborns were stratified into 3 different groups by birth weight (500-749, 750-999, 1000-1250 g) prior to randomization to iNO (10 ppm) or placebo gas (controls) until 30 weeks postmenstrual age. The primary outcome was a composite of death or bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age. Secondary outcomes included the need for and duration of mechanical ventilation, severity of BPD, and safety outcomes.

There was no difference in the incidence of death or BPD in the iNO and placebo groups (42% vs 40%, P = .86, relative risk = 1.06, 0.7-1.6). BPD severity was not different between the treatment groups. There were no differences between the groups in the need for mechanical ventilation (22% vs 23%; P = .89), duration of mechanical ventilation (9.7 vs 8.4 days; P = .27), or safety outcomes including severe intracranial hemorrhage (3.4% vs 6.2%, P = .68).

We found that iNO delivered noninvasively to premature infants who have not progressed to early respiratory failure is a safe treatment, but does not decrease the incidence or severity of BPD, reduce the need for mechanical ventilation, or alter the clinical course.