Association of early inhaled nitric oxide with the survival of preterm neonates with pulmonary hypoplasia

Kevin R. Ellsworth, Marc A. Ellsworth, Amy L. Weaver, Kristin C. Mara, Reese H. Clark, William A. Carey

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 outcomewas 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 [HR], 0.79; 95%CI, 0.57-1.11). 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.

Original languageEnglish (US)
Article numbere180761
JournalJAMA Pediatrics
Volume172
Issue number7
DOIs
StatePublished - Jul 1 2018

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Nitric Oxide
Lung
Pulmonary Hypertension
Mortality
Periventricular Leukomalacia
Puerto Rico
Propensity Score
Retinopathy of Prematurity
Necrotizing Enterocolitis
Neonatal Intensive Care Units
Birth Weight
Lung Diseases
Chronic Disease
Cohort Studies
Outcome Assessment (Health Care)
Clinical Trials
Pregnancy

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Ellsworth, K. R., Ellsworth, M. A., Weaver, A. L., Mara, K. C., Clark, R. H., & Carey, W. A. (2018). Association of early inhaled nitric oxide with the survival of preterm neonates with pulmonary hypoplasia. JAMA Pediatrics, 172(7), [e180761]. https://doi.org/10.1001/jamapediatrics.2018.0761

Association of early inhaled nitric oxide with the survival of preterm neonates with pulmonary hypoplasia. / Ellsworth, Kevin R.; Ellsworth, Marc A.; Weaver, Amy L.; Mara, Kristin C.; Clark, Reese H.; Carey, William A.

In: JAMA Pediatrics, Vol. 172, No. 7, e180761, 01.07.2018.

Research output: Contribution to journalArticle

Ellsworth, KR, Ellsworth, MA, Weaver, AL, Mara, KC, Clark, RH & Carey, WA 2018, 'Association of early inhaled nitric oxide with the survival of preterm neonates with pulmonary hypoplasia', JAMA Pediatrics, vol. 172, no. 7, e180761. https://doi.org/10.1001/jamapediatrics.2018.0761
Ellsworth, Kevin R. ; Ellsworth, Marc A. ; Weaver, Amy L. ; Mara, Kristin C. ; Clark, Reese H. ; Carey, William A. / Association of early inhaled nitric oxide with the survival of preterm neonates with pulmonary hypoplasia. In: JAMA Pediatrics. 2018 ; Vol. 172, No. 7.
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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 outcomewas 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 [HR], 0.79; 95{\%}CI, 0.57-1.11). 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.",
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