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    Association of Early Inhaled Nitric Oxide With the Survival of Preterm Neonates With Pulmonary Hypoplasia

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    Author
    Ellsworth, Kevin R.
    Ellsworth, Marc A.
    Weaver, Amy L.
    Mara, Kristin C.
    Clark, Reese H.
    Carey, William A.
    Affiliation
    Univ Arizona, Dept Child Hlth
    Issue Date
    2018-07
    
    Metadata
    Show full item record
    Publisher
    AMER MEDICAL ASSOC
    Citation
    Ellsworth 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
    Journal
    JAMA PEDIATRICS
    Rights
    Copyright © 2018, American Medical Association
    Collection Information
    This 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 repository@u.library.arizona.edu.
    Abstract
    IMPORTANCE 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.
    Note
    12 month embargo; published online: 7 May 2018
    ISSN
    2168-6203
    PubMed ID
    29800952
    DOI
    10.1001/jamapediatrics.2018.0761
    Version
    Final published version
    Sponsors
    Mayo Clinic Children's Research Center; National Center for Advancing Translational Sciences [UL1 TR002377]
    Additional Links
    http://archpedi.jamanetwork.com/article.aspx?doi=10.1001/jamapediatrics.2018.0761
    ae974a485f413a2113503eed53cd6c53
    10.1001/jamapediatrics.2018.0761
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