Two-Year Outcomes of a Randomized Controlled Trial of Inhaled Nitric Oxide in Premature Infants
BACKGROUND AND OBJECTIVES: The European Union Nitric Oxide trial was designed to assess the potential benefits of inhaled nitric oxide (iNO) compared with placebo in infants with respiratory failure. This follow-up study evaluated respiratory, neurodevelopmental, and other outcomes for infants entered into the European Union Nitric Oxide trial to age 2 years.
METHODS: In a multicenter, randomized, double-blind study, preterm infants born at <29 weeks’ gestation with moderate respiratory failure were allocated to receive iNO (5 ppm) or placebo for 7 to 21 days. Subjects underwent assessments at 1 and 2 years corrected for prematurity.
RESULTS: At 36 weeks’ postmenstrual age, 696 of 792 infants were alive; 4 in the iNO arm subsequently died before age 2 years compared with 7 in the control arm. We evaluated 95% of the survivors at 12 months and 90% at 2 years. In the iNO arm, 244 of 363 (67.2%) infants had survived without disability at age 2 years compared with 270 of 374 (72.2%) who received placebo (P = .094). Mean (SD) cognitive composite scores (Bayley Scales of Infant and Toddler Development, third edition) were 94 (13) in the iNO group and 95 (14) in the placebo group; in the iNO group, 19% scored <85 and 9.5% developed cerebral palsy compared with 13.3% and 9%, respectively. There were no significant differences in hospitalizations overall or due to respiratory illness in use of home oxygen therapy or respiratory medications, in growth, or in other health outcomes.
CONCLUSIONS: At 2 years of age, low-dose (5 ppm) iNO started early (<24 hours after birth) for a median of 20 days did not affect neurodevelopmental or other health outcomes.
- Bayley-III —
- Bayley Scales of Infant and Toddler Development, third edition
- BPD —
- bronchopulmonary dysplasia
- EUNO —
- European Union Nitric Oxide
- GMFCS —
- Gross Motor Function Classification System for Cerebral Palsy
- iNO —
- inhaled nitric oxide
- ROP —
- retinopathy of prematurity
- Accepted June 3, 2013.
- Copyright © 2013 by the American Academy of Pediatrics