Inhaled Nitric Oxide Therapy in the Post-Acute Phase in Extremely Preterm Infants: A Japanese Cohort Study

• Published in: The Journal of pediatrics Vol. 252; pp. 61 - 67.e5
• Main Authors: Nakanishi, Hidehiko, Isayama, Tetsuya, Kokubo, Masayo, Hirano, Shinya, Kusuda, Satoshi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2023
• Subjects: Administration, Inhalation; bronchopulmonary dysplasia; Bronchopulmonary Dysplasia - drug therapy; Cohort Studies; East Asian People; extremely preterm infants; Female; Humans; Infant; Infant, Extremely Premature; Infant, Newborn; Nitric Oxide - therapeutic use; Pregnancy; PPHN; NRNJ; extremely preterm infants; BPD; NICU; iNO; bronchopulmonary dysplasia
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2022.07.057

To determine the trends in inhaled nitric oxide (iNO) utilization in the late phase of hospitalization in a large Japanese cohort of extremely preterm infants and evaluate its benefit on long-term outcomes. This was a retrospective multicenter cohort study of 15 977 extremely preterm infants born at <28 weeks of gestational age between 2003 and 2016, in the Neonatal Research Network, Japan. Demographic characteristics, morbidity, and mortality were compared between extremely preterm infants with and without post-acute iNO therapy. Multivariable logistic analysis was performed to determine factors associated with post-acute iNO and its impact on neurodevelopmental outcomes at 3 years of age. Post-acute iNO utilization rates increased from 0.3% in 2009 to 1.9% in 2016, even under strict insurance coverage rules starting in 2009. Gestational age (1-week increment; aOR 0.82, 95% CI 0.76-0.88), small for gestational age (1.47, 1.08-1.99), histologic chorioamnionitis (1.50, 1.21-1.86), 5-minute Apgar score <4 (1.51, 1.10-2.07), air leak (1.92, 1.30-2.83), and bubbly/cystic appearance on chest X-Ray (1.68, 1.37-2.06) were associated with post-acute iNO. Post-acute iNO was not associated with neurodevelopmental outcomes at 3 years of age. The increasing post-acute iNO utilization rate among extremely preterm infants has been concurrent with improved survival rates of extremely preterm infants in Japan. Infants treated with post-acute iNO had more severe disease and complications than the comparison group, but there were no differences in neurodevelopmental outcome at 3 years. This suggests post-acute iNO may benefit extremely preterm infants.