1. Between 2003 to 2016, there was an increase in both survival and the use of inhaled nitric oxide (iNO) in extremely premature infants in Japan.

2. There were no differences in long-term neurological complications at 3 years of age in iNO and non-iNO treated extremely premature infants.

Evidence Rating Level: 2 (Good)

Study Rundown: Inhaled nitric oxide (iNO) is commonly used in a variety of neonatal conditions such as persistent pulmonary hypertension of the newborn (PPHN), respiratory failure due to bronchopulmonary dysplasia, and pulmonary hypertension. This retrospective cohort study of nearly 16,000 infants detailed how iNO is used post-acutely among extremely preterm infants in Japan without PPHN. During the study period (2013 to 2016), there was an increase in the use of iNO and an increase in the rate of survival in extremely premature infants. Factors such as lower gestational age, histologic chorioamnionitis, 5-minute APGAR score <4, air leak, and bubbly/cystic appearance on chest x-ray were associated with use of iNO. The rates of neurologic complications at 3 years of age did not differ between iNO and non-iNO groups. Because this study is purely descriptive in nature, it does not provide robust evidence regarding the efficacy of iNO in improving mortality or preventing neurologic complications. However, because of its large sample size, it will likely be helpful to neonatologists looking to understand how iNO is used in different parts of the world as part of the management strategy of extremely premature infants.

Click here to read the article in the Journal of Pediatrics

Relevant Reading: Association of Early Inhaled Nitric Oxide With the Survival of Preterm Neonates With Pulmonary Hypoplasia

In Depth [Retrospective Cohort]: This retrospective cohort study included 15,977 extremely premature (<28 weeks of age) infants from the Neonatal Research Network, Japan between 2003 and 2016. Neurodevelopmental assessments were the primary outcomes at 3 years of age and included: cerebral palsy, visual impairment, hearing impairment, neurodevelopmental delay and cognitive impairments. During the study period, the use of iNO in extremely preterm infants increased from 3.3% to 13.4% (p<0.001). The survival rate of extremely preterm infants increased from 79.9% to 91.7% (p<0.001) during the same period. Multivariable regression analysis was performed on neonatal factors as predictors of use of iNO, including: gestational age, sex, multiple pregnancy, small for gestational age, AGPAR scores, chorioamnionitis, sepsis, severe bronchopulmonary dysplasia, severe retinopathy of prematurity, severe intraventricular hemorrhage, and periventricular leukomalacia. The factors associated with use of iNO included gestational age (in one week increments; OR 0.82, 95% CI 0.76-0.88, p<0.001), histologic chorioamnionitis (OR 1.50, 195% CI .21-1.86, p<0.001), 5-minute APGAR score <4 (OR 1.51, 95% CI 1.10-2.07, p= 0.011), air leak (OR 1.92, 95% CI 1.30-2.83, p= 0.001), and cystic appearance on chest x-ray (OR 1.68, 95% CI 1.37-2.06, p<0.001). Long-term neurological outcomes were assessed at 3 years of age and did not differ between the groups for the following outcomes: rates of cerebral palsy, visual impairment, hearing impairment, Kyoto Scale of Psychological Development, and neurodevelopmental impairments.

Image: PD

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