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Updated: Oct 11, 2025

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Published on: May 4, 2021
Epidemiologic evaluation of inhaled nitric oxide use among neonates with gestational age less than 35 weeks
Allison M Peluso1, Hasan F Othman2, Sreenivas Karnati1
1Department of Neonatology, Cleveland Clinic Children's Hospital, Cleveland, Ohio, USA.
Insights
Inhaled nitric oxide (iNO) use increased in preterm infants after 2010, with lower mortality but doubled costs. This suggests targeted iNO use for high-risk neonates may improve survival.
Area of Science:
- Neonatal Medicine
- Pediatric Pulmonology
- Critical Care
Background:
- Inhaled nitric oxide (iNO) is FDA-approved for late preterm and term infants with pulmonary hypertension, improving outcomes.
- iNO is not FDA-approved for preterm infants, and prior studies showed no mortality benefit in this population.
Purpose of the Study:
- To determine the usage trends of iNO in preterm neonates (<35 weeks) before and after a 2010 consensus statement.
- To evaluate the characteristics and outcomes of preterm neonates who received iNO.
Main Methods:
- Population-based, cross-sectional study using National Inpatient Sample data (2004-2016).
- iNO usage determined via billing and procedure codes for neonates <35 weeks gestational age.
- Data divided into two epochs: 2004-2010 and 2011-2016.
Main Results:
- Significant increase in iNO use from 2011-2016 compared to 2004-2010 (p<0.001).
- Higher iNO use in Epoch 2 observed in neonates with small for gestational age (SGA), congenital heart disease (CHD), and bronchopulmonary dysplasia (BPD).
- Mortality was significantly lower in Epoch 2 (19.8%) versus Epoch 1 (22.7%).
Conclusions:
- iNO usage in preterm neonates increased after the 2010 consensus statement.
- Increased iNO use may be targeted towards high-risk populations like SGA and CHD neonates.
- Lower mortality in Epoch 2 was accompanied by a doubled hospitalization cost.
Background And Objectives:
The use of inhaled nitric oxide (iNO) in +late preterm and term infants with pulmonary hypertension is Food and Drug Administration (FDA) approved and has improved outcomes and survival. iNO use is not FDA approved for preterm infants and previous studies show no mortality benefit. The objectives were 1) to determine the usage of iNO among preterm neonates <35 weeks before and after the 2010 National Institutes of Health consensus statement and 2) to evaluate characteristics and outcomes among preterm neonates who received iNO.
Methods:
This is a population-based cross-sectional study. Billing and procedure codes were used to determine iNO usage. Data were queried from the National Inpatient Sample from 2004 to 2016. Neonates were included if gestational age was <35 weeks. The epochs were spilt into 2004-2010 (Epoch 1) and 2011-2016 (Epoch 2). Prevalence of iNO use, mortality, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage, length of stay, mechanical ventilation, and cost of hospitalization.
Results:
There were 4865 preterm neonates <35 weeks who received iNO. There was a significant increase in iNO use during Epoch 2 (p < 0.001). There was significantly higher use in Epoch 2 among neonates small for gestational age (SGA) 2.3% versus 7.2%, congenital heart disease (CHD) 11.1% versus 18.6%, and BPD 35.2% versus 46.8%. Mortality was significantly lower in Epoch 2 19.8% versus 22.7%.
Conclusion:
Usage of iNO was higher after the release of the consensus statement. The increased use of iNO among preterm neonates may be targeted at specific high-risk populations such as SGA and CHD neonates. There was lower mortality in Epoch 2; however, the cost was doubled.
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