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Inhaled Nitric Oxide Therapy in the Post-Acute Phase in Extremely Preterm Infants: A Japanese Cohort Study
Hidehiko Nakanishi1, Tetsuya Isayama2, Masayo Kokubo3
1Research and Development Center for New Medical Frontiers, Department of Advanced Medicine, Division of Neonatal Intensive Care Medicine, Kitasato University School of Medicine, Kanagawa, Japan.
Insights
Utilization of inhaled nitric oxide (iNO) in extremely preterm infants increased, but did not impact 3-year neurodevelopmental outcomes. This suggests iNO may benefit these infants despite more severe disease.
Area of Science:
- Neonatal Medicine
- Pediatric Pulmonology
- Clinical Research
Background:
- Extremely preterm infants (<28 weeks) face significant short- and long-term morbidities.
- Inhaled nitric oxide (iNO) is used to treat pulmonary hypertension in neonates.
- Trends and long-term outcomes of post-acute iNO in this population are not well-defined.
Purpose of the Study:
- To analyze trends in post-acute inhaled nitric oxide (iNO) utilization in extremely preterm infants in Japan.
- To evaluate the association of post-acute iNO with factors like gestational age, birth weight, and complications.
- To assess the impact of post-acute iNO on neurodevelopmental outcomes at 3 years of age.
Main Methods:
- Retrospective multicenter cohort study of 15,977 extremely preterm infants (2003-2016).
- Comparison of demographic characteristics, morbidity, and mortality between infants with and without post-acute iNO.
- Multivariable logistic analysis to identify factors associated with post-acute iNO and its effect on neurodevelopment.
Main Results:
- Post-acute iNO utilization increased from 0.3% (2009) to 1.9% (2016).
- Factors associated with post-acute iNO included lower gestational age, small for gestational age, histologic chorioamnionitis, low Apgar score, air leak, and chest X-ray findings.
- No significant difference in 3-year neurodevelopmental outcomes was observed between groups.
Conclusions:
- Increasing post-acute iNO use in extremely preterm infants coincided with improved survival rates.
- Infants receiving post-acute iNO had more severe disease but similar neurodevelopmental outcomes at 3 years.
- Post-acute iNO may offer benefits for extremely preterm infants, warranting further investigation.
Objective:
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.
Study Design:
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.
Results:
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.
Conclusions:
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.
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