Hasan SU, et al. - This research investigated if the administration of inhaled nitric oxide to preterm infants requiring positive pressure respiratory support on postnatal days 5 to 14 led to an improvement in the rate of survival without bronchopulmonary dysplasia (BPD). It was deduced that the inhaled nitric oxide, initiated at 20 ppm on postnatal days 5 to 14 to high-risk preterm infants and continued for 24 days, was safe. Nevertheless, it did not improve the survival without BPD at 36 weeks' postmenstrual age (PMA) or respiratory and neurodevelopmental outcomes at 18 to 24 months’ PMA.

Methods

• The scheme of this intent-to-treat study was a randomized clinical trial.
• It was carried out at 33 US and Canadian neonatal intensive care units.
• 451 neonates younger than 30 weeks’ gestation with birth weight less than 1250 g were recruited.
• They received mechanical ventilation or positive pressure respiratory support on postnatal days 5 to 14.
• Enrollment spanned from December 23, 2009, to April 23, 2012, and neurodevelopmental outcome studies were completed by April 4, 2014.
• As a part of the intervention, placebo (nitrogen) or inhaled nitric oxide initiated at 20 ppm was decreased to 10 ppm between 72 and 96 hours after starting treatment and then to 5 ppm on day 10 or 11.
• Infants remained on the 5-ppm dose until completion of therapy (24 days).
• The primary outcome comprised of the rate of survival without BPD at 36 weeks’ postmenstrual age (PMA).
• BPD severity, postnatal corticosteroid use, respiratory support, survival, and neurodevelopmental outcomes at 18 to 24 months’ PMA were the secondary outcomes.

Results

• 222 infants (52.3% male [n = 116]) received placebo, and 229 infants (50.2% male [n = 115]) received inhaled nitric oxide.
• Their mean (SD) gestation was 25.6 (1.5) vs 25.6 (1.4) weeks, and their mean (SD) birth weight was 750 (164) vs 724 (160) g.
• Survival without BPD at 36 weeks’ PMA appeared to be similar among the placebo and inhaled nitric oxide groups (31.5% [n = 70] vs 34.9% [n = 80]) (odds ratio, 1.17; 95% CI, 0.79-1.73). Rates for severe BPD (26.6% [55 of 207] vs 20.5% [43 of 210]) and postnatal corticosteroid use for BPD (41.0% [91 of 222] vs 41.5% [95 of 229]) and the mean (SD) days of positive pressure respiratory support (55 [40] vs 54 [42]), oxygen therapy (88 [41] vs 91 [59]), and hospitalization (105 [37] vs 108 [54]) were equivalent between the 2 groups.
• There were no variations in the incidence of common morbidities.
• Respiratory outcomes on discharge to home, at 1 year, and at age 18 to 24 months’ PMA and neurodevelopmental assessments at 18 to 24 months’ PMA did not vary among the groups.