Dataset Information

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

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 [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.

SUBMITTER: Ellsworth KR

PROVIDER: S-EPMC6137510 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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

Ellsworth Kevin R KR Ellsworth Marc A MA Weaver Amy L AL Mara Kristin C KC Clark Reese H RH Carey William A WA

JAMA pediatrics 20180702 7

<h4>Importance</h4>Pulmonary hypoplasia affects a very small percentage of preterm neonates, but its presence is associated with high rates of mortality.<h4>Objective</h4>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.<h4>Design, setting, and participants</h4>This cohort study used data from the Pediatrix Medical Group's Clinical Data Wareh ...[more]

PMID: 29800952

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Project description:Importance:Bronchopulmonary dysplasia (BPD) occurs in approximately 40% of infants born at younger than 30 weeks' gestation and is associated with adverse pulmonary and neurodevelopmental outcomes. Objective:To test whether administration of inhaled nitric oxide to preterm infants requiring positive pressure respiratory support on postnatal days 5 to 14 improves the rate of survival without BPD. Design, Setting, and Participants:This intent-to-treat study was a randomized clinical trial performed at 33 US and Canadian neonatal intensive care units. Participants included 451 neonates younger than 30 weeks' gestation with birth weight less than 1250 g receiving mechanical ventilation or positive pressure respiratory support on postnatal days 5 to 14. Enrollment spanned from December 23, 2009, to April 23, 2012, and neurodevelopmental outcome studies were completed by April 4, 2014. Interventions:Placebo (nitrogen) or inhaled nitric oxide initiated at 20 ppm was decreased to 10 ppm between 72 and 96 hours after starting treatment and then to 5 ppm on day 10 or 11. Infants remained on the 5-ppm dose until completion of therapy (24 days). Main Outcomes and Measures:The primary outcome was the rate of survival without BPD at 36 weeks' postmenstrual age (PMA). Secondary outcomes included BPD severity, postnatal corticosteroid use, respiratory support, survival, and neurodevelopmental outcomes at 18 to 24 months' PMA. Results:In total, 222 infants (52.3% male [n?=?116]) received placebo, and 229 infants (50.2% male [n?=?115]) received inhaled nitric oxide. Their mean (SD) gestation was 25.6 (1.5) vs 25.6 (1.4) weeks, and their mean (SD) birth weight was 750 (164) vs 724 (160) g. Survival without BPD at 36 weeks' PMA was similar between the placebo and inhaled nitric oxide groups (31.5% [n?=?70] vs 34.9% [n?=?80]) (odds ratio, 1.17; 95% CI, 0.79-1.73). Rates for severe BPD (26.6% [55 of 207] vs 20.5% [43 of 210]) and postnatal corticosteroid use for BPD (41.0% [91 of 222] vs 41.5% [95 of 229]) and the mean (SD) days of positive pressure respiratory support (55 [40] vs 54 [42]), oxygen therapy (88 [41] vs 91 [59]), and hospitalization (105 [37] vs 108 [54]) were equivalent between the 2 groups. No differences in the incidence of common morbidities were observed. Respiratory outcomes on discharge to home, at 1 year, and at age 18 to 24 months' PMA and neurodevelopmental assessments at 18 to 24 months' PMA did not differ between groups. Conclusions and Relevance:Inhaled nitric oxide, initiated at 20 ppm on postnatal days 5 to 14 to high-risk preterm infants and continued for 24 days, appears to be safe but did not improve survival without BPD at 36 weeks' PMA or respiratory and neurodevelopmental outcomes at 18 to 24 months' PMA. Trial Registration:clinicaltrials.gov Identifier: NCT00931632.

Project description:BACKGROUND:Substantial numbers of neonates with hypoxic respiratory failure (HRF) do not immediately respond to inhaled nitric oxide (iNO) and are often labeled as non-responders. This retrospective data analysis assessed time to treatment response in the iNO key registration trial. METHODS:Treatment response was defined as a??10% increase in partial pressure of arterial oxygen (PaO2) or a??10% decrease in oxygenation index (OI) after initiation of study gas without the need for extracorporeal membrane oxygenation (ECMO). The proportion of patients showing a response at 30?min, 1?h, 24?h, and?>24?h after iNO or placebo initiation was calculated and stratified by baseline PaO2 and OI. RESULTS:Data from 248 patients (iNO: n =?126; placebo: n =?122) were included; 66 patients receiving iNO showed improvement in oxygenation without needing ECMO versus 38 receiving placebo. Of the 66 iNO responders, 73% responded within ?30?min, 9% within ?1?h, 12% within ?24?h, and 6% after 24?h. Of the 38 patients with improvement in oxygenation without needing ECMO while receiving placebo, 53% showed improvement within ?30?min, 16% within ?1?h, 29% within ?24?h, and 3% after 24?h. Baseline disease severity was not predictive of time to response. Of the 48 patients in the iNO treatment group who were classified as non-responders due to eventual need for ECMO and not included in the analysis of responders, 40 (83%) had an initial improvement in oxygenation during iNO therapy. CONCLUSIONS:Changes in PaO2 and OI after iNO initiation appear to be imprecise biomarkers of response to therapy in neonates with HRF. In some patients treated with iNO, it took up to 24?h to achieve improvement in oxygenation without need for ECMO, and a majority of those who eventually required ECMO did show an initial improvement in oxygenation during iNO treatment. Thus, reliable, objective, early criteria for iNO response still need to be established, and initial PaO2/OI responses should be interpreted with caution, particularly when considering discontinuing iNO therapy.

Dataset Information

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

Publications

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

Similar Datasets

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