Inhaled nitric oxide in premature infants shows no benefits

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1. Premature infants given inhaled nitric oxide (iNO) within 24 hours of birth showed no significant respiratory or neurodevelopmental differences at 12 months and 2 years corrected age when compared to controls. 

Evidence Rating Level: 1 (Excellent)       

Study Rundown: Bronchopulmonary dysplasia (BPD) is a common complication of premature birth in which inflammation and scarring of the lungs leads to oxygen dependence in infancy and sometimes beyond. While mortality amongst premature infants with BPD has continued to improve, they still have high morbidity secondary to respiratory and neurodevelopmental issues. iNO, given in the perinatal period, has been evaluated in the prevention of BPD-related complications. Studies in animal models have suggested iNO may aid in continued alveolar development; however, results of similar studies in clinical trials have been equivocal. The European Union Nitric Oxide (EUNO) trial is a previously published, randomized control trial that found no significant differences in neonatal mortality or morbidity between premature infants receiving iNO versus controls. The current study is a EUNO follow-up, evaluating the original study group now at 12 months and 2 years corrected age. No significant differences in terms of neurodevelopmental assessments, hospitalizations, or growth were found. This study is limited by its inclusion of a homogenous population. Continued follow-up with the study population will occur again at 7 years corrected age for further neurodevelopmental assessments.

Click to read the study, published today in Pediatrics

Relevant Reading: Neurodevelopmental outcomes of premature infants treated with inhaled nitric oxide

In-Depth [randomized control trial]: This study follows participants from the original EUNO trial, which included 792 premature infants between 24 and 28 weeks gestational age. Infants in the trial arm were given low-dose, 5 parts per million (ppm) iNO within 24 hours of birth, and continued on iNO for a median of 20 days. Control infants received placebo. 696 infants survived to 36 weeks corrected age. These 696 infants were considered for follow-up study with 95% evaluated at 12 months and 90% at 2 years corrected age. An additional 11 infants died between 36 months and 2 years and were excluded from analyses. Neurodevelopmental assessments using the Bayley-III tool were conducted.  No significant differences in cerebral palsy, seizures, hearing, vision, or retinopathy of prematurity were seen between groups. Additionally, differences in growth and rates of hospitalization, including for respiratory complications, were not significant.

By Neha Joshi and Leah H. Carr

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