The use of inhaled nitric oxide in premature infants without bronchopulmonary dysplasia (BPD) appears to be safe, but it does not improve survival rates at 36 weeks’ postmenstrual age (PMA) or neurodevelopmental or respiratory outcomes at 18 to 24 months’ PMA.
An intent-to-treat, randomized, placebo-controlled trial (Newborns Treated With Nitric Oxide; ClinicalTrials.gov identifier: NCT00931632), published in JAMA Pediatrics, sought to investigate whether the administration of inhaled nitric oxide to preterm newborns on postnatal days 5 to 14 is associated with improvements in survival.
The study was conducted at 33 neonatal intensive care units in the United States and Canada. Participants comprised 451 infants <30 weeks’ gestation with birth weights <1250 grams, who received positive pressure respiratory support or mechanical ventilation on postnatal days 5 to 14. Study participants received placebo (nitrogen) or inhaled nitric oxide, initiated at 20 parts per million (ppm), then decreased to 10 ppm between 72 and 96 hours after starting treatment, and then reduced to 5 ppm on day 10 or 11. The newborns continued the 5 ppm dose for 24 days.
The primary outcome was the rate of infant survival without BPD at 36 weeks’ PMA. Secondary outcomes included severity of BPD, postnatal corticosteroid use, respiratory support, survival, and neurodevelopmental outcomes at 18 to 24 months’ PMA.
Overall, 222 infants received placebo and 229 infants received inhaled nitric oxide. The newborns’ mean gestational age was 25.6±1.5 weeks vs 25.6±1.4 weeks, respectively. Mean birth weight was 750±164 grams vs 724±160 grams, respectively. Survival without BPD at 36 weeks’ PMA was similar between the 2 groups (31.5% [n=70] vs 34.9% [n=80], respectively; odds ratio, 1.17; 95% CI, 0.79-1.73).
Rates of severe BPD (26.6% [55 of 207] vs 20.5% [43 of 210], respectively) and postnatal corticosteroid use (41.0% [91 of 222] vs 41.5% [95 of 229], respectively) were equivalent between the 2 arms, as were the mean days of positive pressure respiratory support (55±40 days vs 54±42 days, respectively), oxygen therapy (88±41 days vs 91±59 days, respectively), and hospitalization (105±37 days vs 108±54 days, respectively).
No differences in the occurrence of common morbidities were reported. Respiratory outcomes at discharge to home, at 1 year, and at 18 to 24 months’ PMA, as well as neurodevelopmental evaluations at 18 to 24 months’ PMA, also did not differ between the groups.
The investigators concluded that inhaled nitric oxide is safe but does not improve survival without BPD at 36 weeks’ PMA or neurodevelopmental and respiratory outcomes at 18 to 24 weeks’ PMA.
Disclosures: This study was funded by Mallinckrodt Pharmaceuticals.
Hasan SU, Potenziano J, Konduri GG, et al; for the Newborns Treated With Nitric Oxide (NEWNO) Trial Group. Effect of inhaled nitric oxide on survival without bronchopulmonary dysplasia in preterm infants: a randomized clinical trial [published online September 25, 2017]. JAMA Pediatr. doi:10.1001/jamapediatrics.2017.2618