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Updated: Sep 9, 2025

A Novel Inhalation Mask System to Deliver High Concentrations of Nitric Oxide Gas in Spontaneously Breathing Subjects
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Inhaled nitric oxide in preterm infants with respiratory disease: a systematic review and meta-analysis

Kai Zhou1,2, Weipeng Xu3, Danrui Li3

  • 1Faculty of Medicine, International School, Jinan University, Guangzhou, Guangdong, China.

European Journal of Medical Research
|August 28, 2025
PubMed

Insights

Inhaled nitric oxide (iNO) may reduce death or bronchopulmonary dysplasia (BPD) in preterm infants. However, it increases the risk of retinopathy of prematurity, and long-term outcomes require further study.

Area of Science:

  • Neonatal Medicine
  • Respiratory Medicine
  • Pharmacology

Background:

  • Inhaled nitric oxide (iNO) is effective in term infants but has different risks/benefits in preterm infants.
  • Preterm infants have unique pathophysiology requiring specific investigation for iNO.
  • Further research is essential to understand iNO's role in this vulnerable population.

Purpose of the Study:

  • To evaluate the short-term and long-term effects of iNO in preterm infants.
  • To assess iNO's efficacy in treating respiratory failure and respiratory distress syndrome.
  • To determine the safety profile of iNO in preterm neonates.

Main Methods:

  • A meta-analysis of randomized controlled trials and cohort studies was performed.
  • Searched major databases (PubMed, Cochrane, Scopus, Web of Science) until May 2025.
  • Primary outcomes included mortality and bronchopulmonary dysplasia (BPD) at various time points.

Main Results:

  • iNO use was linked to a reduced risk of death or BPD (RR 0.94) and BPD in RCTs (RR 0.91).
  • Improved oxygenation index and PaO2 were observed with initial iNO concentrations of 5 ppm.
  • An increased risk of retinopathy of prematurity was noted (RR 1.08), with no significant differences in other morbidities.

Conclusions:

  • iNO appears to reduce the risk of death or BPD and likely reduces BPD in preterm infants.
  • No significant impact on other neonatal morbidities or adverse events was found.
  • Long-term respiratory and neurodevelopmental data are crucial for a comprehensive assessment of iNO in preterm infants, especially extremely low birth weight infants.
Abstract

Keywords:
Bronchopulmonary dysplasiaDeathInhaled nitric oxideMeta-analysisPreterm infants

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