Annals of Clinical Epidemiology
Online ISSN : 2434-4338
Inhaled nitric oxide for preterm infants with persistent pulmonary hypertension
Takeshi KimuraMasatoshi NozakiJun ShiraishiKazuko WadaHiroyuki KitajimaNeonatal Research Network of Japan
ジャーナル オープンアクセス HTML

2019 年 1 巻 1 号 p. 18-27



Systematic reviews and other studies have not supported the routine use of inhaled nitric oxide (iNO) for preterm infants with respiratory failure. However, despite the lack of evidence, many physicians use iNO for a subgroup of preterm infants with respiratory failure, such as cases of persistent pulmonary hypertension of the newborn (PPHN). This study aimed to clarify whether the use of iNO improved the mortality rate among preterm infants with PPHN.


We analyzed data from the Neonatal Research Network in Japan, which is a population-based nationwide registry. The study included neonates who were born at <32 weeks of gestational age between 2006 and 2012 and were diagnosed with PPHN without major congenital malformation including serious congenital heart disease. The primary outcome was the in-hospital mortality rate. Confounder-adjusted odds ratios were estimated using mixed effects logistic regression accounting for clustering within hospitals as random effects and covariates as fixed effects.


We identified 1,231 eligible infants, including 739 infants (60%) who received iNO. iNO did not significantly improve mortality (odds ratio [OR]: 1.13, 95% confidence interval [CI]: 0.82–1.55, P = 0.45). iNO was significantly associated with bronchopulmonary dysplasia (OR: 1.50, 95% CI: 1.11–2.02, P = <0.01) and retinopathy of prematurity requiring treatment (OR: 1.56, 95% CI: 1.11–2.19, P = 0.01).


This retrospective study failed to detect an association between iNO treatment and improved survival among preterm infants with PPHN, however, there are several limitations in this study. Further research is required in this area.

© 2019 Society for Clinical Epidemiology