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Published on: October 11, 2011
Inhaled nitric oxide for preterm infants: a systematic review
Keith J Barrington1, Neil N Finer
1Department of Pediatrics, McGill University, Royal Victoria Hospital, 687 Pine Ave W, Montreal, Quebec, Canada H3A 1A1. keith.barrington@mcgill.ca
Insights
Inhaled nitric oxide may not effectively treat very sick preterm infants and could increase brain bleeds. However, early routine use in milder cases may reduce brain injury and improve survival without bronchopulmonary dysplasia.
Area of Science:
- Neonatal Medicine
- Respiratory Medicine
- Pediatric Critical Care
Background:
- Preterm infants often suffer from respiratory distress.
- Bronchopulmonary dysplasia (BPD) and intracranial hemorrhage (ICH) are significant morbidities in preterm infants.
- Inhaled nitric oxide (iNO) has been explored as a therapeutic agent for respiratory conditions in newborns.
Purpose of the Study:
- To evaluate the efficacy of inhaled nitric oxide in reducing mortality, BPD, ICH, or neurodevelopmental disability in preterm infants with respiratory disease.
- To analyze the impact of iNO based on different treatment timings and infant severity.
Main Methods:
- A systematic review and meta-analysis of eleven randomized controlled trials (RCTs) were conducted.
- Trials were identified through comprehensive searches of major medical databases (Medline, Embase, Healthstar, Cochrane) and conference abstracts (1985-2006).
- Studies were categorized based on iNO administration timing (early rescue, later, or routine use) and infant criteria.
Main Results:
- Early rescue iNO for severely ill preterm infants did not improve mortality or BPD rates and showed a trend towards increased severe ICH.
- Routine iNO for intubated preterm infants demonstrated a significant reduction in the combined outcome of death or BPD (RR: 0.91).
- Routine iNO in preterm infants also suggested a reduction in severe ICH or periventricular leukomalacia (RR: 0.70).
Conclusions:
- Inhaled nitric oxide as rescue therapy for critically ill preterm infants is not effective and may increase the risk of severe intracranial hemorrhage.
- Later use of iNO to prevent bronchopulmonary dysplasia lacks significant efficacy.
- Early routine administration of iNO for mildly ill preterm infants appears to decrease the risk of serious brain injury and may enhance survival rates free from BPD.
Objective:
Our goal was to determine whether, for preterm newborn infants with respiratory disease, inhaled nitric oxide reduced the rates of death, bronchopulmonary dysplasia, intracranial hemorrhage, or neurodevelopmental disability.
Methods:
We searched Medline, Embase, Healthstar, and the Cochrane Central Register of Controlled Trials using the search terms "nitric oxide," "clinical trial," and "newborn" and covering 1985-2006. We also searched abstracts of the Pediatric Academic Societies.
Results:
Eleven randomized, controlled trials of inhaled nitric oxide therapy for preterm infants were found. The trials were grouped into 3 categories according to the entry criteria, that is, entry in the first 3 days of life on the basis of oxygenation criteria (early rescue), enrollment after 3 days on the basis of elevated risk of bronchopulmonary dysplasia, and routine use for intubated preterm infants. Early rescue treatment based on oxygenation criteria did not seem to affect mortality or bronchopulmonary dysplasia rates. Routine use for intubated preterm infants showed a barely significant reduction in the incidence of the combined outcome of death or bronchopulmonary dysplasia (relative risk [RR]: 0.91 [95% confidence limits (CLs): 0.84, 0.99]). Later treatment based on the risk of bronchopulmonary dysplasia showed no significant effect on this outcome. Early rescue treatment showed a trend toward increased incidence of severe intracranial hemorrhage, whereas routine use for intubated preterm infants seemed to show a reduction in the incidence of either severe intracranial hemorrhage or periventricular leukomalacia (RR: 0.70 [95% CLs: 0.53, 0.91]).
Conclusions:
Inhaled nitric oxide as rescue therapy for very ill preterm infants undergoing ventilation does not seem to be effective and may increase severe intracranial hemorrhage. Later use of inhaled nitric oxide to prevent bronchopulmonary dysplasia does not seem to be effective. Early routine use of inhaled nitric oxide for mildly sick, preterm infants seems to decrease the risk of serious brain injury and may improve rates of survival without bronchopulmonary dysplasia.
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