Effect of Inhaled Nitric Oxide on Survival Without Bronchopulmonary Dysplasia in Preterm Infants: A Randomized Clinical Trial. JAMA Pediatr 2017 Nov 01;171(11):1081-1089
Date
10/04/2017Pubmed ID
28973344Pubmed Central ID
PMC5710365DOI
10.1001/jamapediatrics.2017.2618Scopus ID
2-s2.0-85034748298 (requires institutional sign-in at Scopus site) 49 CitationsAbstract
IMPORTANCE: Bronchopulmonary dysplasia (BPD) occurs in approximately 40% of infants born at younger than 30 weeks' gestation and is associated with adverse pulmonary and neurodevelopmental outcomes.
OBJECTIVE: To test whether administration of inhaled nitric oxide to preterm infants requiring positive pressure respiratory support on postnatal days 5 to 14 improves the rate of survival without BPD.
DESIGN, SETTING, AND PARTICIPANTS: This intent-to-treat study was a randomized clinical trial performed at 33 US and Canadian neonatal intensive care units. Participants included 451 neonates younger than 30 weeks' gestation with birth weight less than 1250 g receiving 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.
INTERVENTIONS: 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).
MAIN OUTCOMES AND MEASURES: The primary outcome was the rate of survival without BPD at 36 weeks' postmenstrual age (PMA). Secondary outcomes included BPD severity, postnatal corticosteroid use, respiratory support, survival, and neurodevelopmental outcomes at 18 to 24 months' PMA.
RESULTS: In total, 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 was similar between 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. No differences in the incidence of common morbidities were observed. 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 differ between groups.
CONCLUSIONS AND RELEVANCE: Inhaled nitric oxide, initiated at 20 ppm on postnatal days 5 to 14 to high-risk preterm infants and continued for 24 days, appears to be safe but did not improve survival without BPD at 36 weeks' PMA or respiratory and neurodevelopmental outcomes at 18 to 24 months' PMA.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00931632.
Author List
Hasan SU, Potenziano J, Konduri GG, Perez JA, Van Meurs KP, Walker MW, Yoder BA, Newborns Treated With Nitric Oxide (NEWNO) Trial GroupAuthor
Girija Ganesh Konduri MD Chief, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Administration, InhalationBronchodilator Agents
Bronchopulmonary Dysplasia
Double-Blind Method
Drug Administration Schedule
Female
Humans
Infant, Newborn
Infant, Premature
Infant, Premature, Diseases
Intention to Treat Analysis
Male
Nitric Oxide
Positive-Pressure Respiration
