Association of Early Inhaled Nitric Oxide With the Survival of Preterm Neonates With Pulmonary Hypoplasia
AuthorEllsworth, Kevin R.
Ellsworth, Marc A.
Weaver, Amy L.
Mara, Kristin C.
Clark, Reese H.
Carey, William A.
AffiliationUniv Arizona, Dept Child Hlth
MetadataShow full item record
PublisherAMER MEDICAL ASSOC
CitationEllsworth KR, Ellsworth MA, Weaver AL, Mara KC, Clark RH, Carey WA. Association of Early Inhaled Nitric Oxide With the Survival of Preterm Neonates With Pulmonary Hypoplasia. JAMA Pediatr. 2018;172(7):e180761. doi:10.1001/jamapediatrics.2018.0761
RightsCopyright © 2018, American Medical Association
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractIMPORTANCE Pulmonary hypoplasia affects a very small percentage of preterm neonates, but its presence is associated with high rates of mortality. OBJECTIVE To determine whether treatment with inhaled nitric oxide during the first week of life was associated with improved in-hospital survival in a cohort of extremely preterm neonates with pulmonary hypoplasia. DESIGN, SETTING, AND PARTICIPANTS This cohort study used data from the Pediatrix Medical Group's Clinical Data Warehouse, a data set containing information from more than 350 neonatal intensive care units in 35 US states and Puerto Rico. Since inhaled nitric oxide was not randomly prescribed, we used 1-to-1 propensity score matching to reduce the imbalance of measured covariates between the 2 treatment groups. The initial, unmatched cohort included singleton neonates who were born between 22 and 29 weeks' gestation, had a birth weight of 400 g or more, were diagnosed with pulmonary hypoplasia as a cause of their respiratory distress, remained free of major anomalies, and were discharged between January 1, 2000, and December 31, 2014. We defined exposure as the initiation of inhaled nitric oxide on day t in days 0 to 7 of the life of a neonate. Each exposed neonate was matched 1-to-1 to a neonate who had not initiated inhaled nitric oxide on a given day. MAIN OUTCOMES AND MEASURES The primary outcome was mortality defined as death prior to transfer or discharge home. Secondary outcomes were any-stage necrotizing enterocolitis, retinopathy of prematurity requiring treatment, chronic lung disease, and periventricular leukomalacia. RESULTS Among 92 635 neonates in our study sample, we identified 767 (0.8%) with pulmonary hypoplasia who met all study inclusion criteria, of whom 185 (0.2%) were exposed to inhaled nitric oxide. Among 151 matched pairs of exposed and unexposed neonates, we did not identify a significant association between inhaled nitric oxide use and mortality (hazard ratio [NM, 079; 95% CI, 0.57411). Subgroup analyses of neonates with and without persistent pulmonary hypertension (PPHN) likewise revealed no significant association between inhaled nitric oxide use and mortality (pulmonary hypoplasia with PPHN: HR, 0.67; 95% CI, 0.45-1.01; pulmonary hypoplasia without PPHN: HR, 1.11; 95% CI, 0.61-2.02), but these findings may have been influenced by ascertainment bias. CONCLUSIONS AND RELEVANCE Early treatment with inhaled nitric oxide is not associated with improved survival among extremely preterm neonates with pulmonary hypoplasia. Clinical trials are warranted to clarify the matter.
Note12 month embargo; published online: 7 May 2018
VersionFinal published version
SponsorsMayo Clinic Children's Research Center; National Center for Advancing Translational Sciences [UL1 TR002377]
- Effect of Inhaled Nitric Oxide on Survival Without Bronchopulmonary Dysplasia in Preterm Infants: A Randomized Clinical Trial.
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- Outcomes of early inhaled nitric oxide use in premature African American neonates.
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- Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: a randomised controlled trial.
- Authors: Kinsella JP, Walsh WF, Bose CL, Gerstmann DR, Labella JJ, Sardesai S, Walsh-Sukys MC, McCaffrey MJ, Cornfield DN, Bhutani VK, Cutter GR, Baier M, Abman SH
- Issue date: 1999 Sep 25
- The changing pattern of inhaled nitric oxide use in the neonatal intensive care unit.
- Authors: Clark RH, Ursprung RL, Walker MW, Ellsbury DL, Spitzer AR
- Issue date: 2010 Dec
- Inhaled Nitric Oxide in Extremely Premature Neonates With Respiratory Distress Syndrome.
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