RESUMO
OBJECTIVE: To determine the effects of late surfactant on respiratory outcomes determined at 1-year corrected age in the Trial of Late Surfactant (TOLSURF), which randomized newborns of extremely low gestational age (≤28 weeks' gestational age) ventilated at 7-14 days to late surfactant and inhaled nitric oxide vs inhaled nitric oxide-alone (control). STUDY DESIGN: Caregivers were surveyed in a double-blinded manner at 3, 6, 9, and 12 months' corrected age to collect information on respiratory resource use (infant medication use, home support, and hospitalization). Infants were classified for composite outcomes of pulmonary morbidity (no PM, determined in infants with no reported respiratory resource use) and persistent PM (determined in infants with any resource use in ≥3 surveys). RESULTS: Infants (n = 450, late surfactant n = 217, control n = 233) were 25.3 ± 1.2 weeks' gestation and 713 ± 164 g at birth. In the late surfactant group, fewer infants received home respiratory support than in the control group (35.8% vs 52.9%, relative benefit [RB] 1.28 [95% CI 1.07-1.55]). There was no benefit of late surfactant for No PM vs PM (RB 1.27; 95% CI 0.89-1.81) or no persistent PM vs persistent PM (RB 1.01; 95% CI 0.87-1.17). After adjustment for imbalances in baseline characteristics, relative benefit of late surfactant treatment increased: RB 1.40 (95% CI 0.89-1.80) for no PM and RB 1.24 (95% CI 1.08-1.42) for no persistent PM. CONCLUSION: Treatment of newborns of extremely low gestational age with late surfactant in combination with inhaled nitric oxide decreased use of home respiratory support and may decrease persistent pulmonary morbidity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01022580.
Assuntos
Recém-Nascido de Peso Extremamente Baixo ao Nascer , Óxido Nítrico/administração & dosagem , Surfactantes Pulmonares/administração & dosagem , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Administração por Inalação , Fatores Etários , Displasia Broncopulmonar/prevenção & controle , Intervalos de Confiança , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Masculino , Síndrome do Desconforto Respiratório do Recém-Nascido/diagnóstico , Medição de Risco , Taxa de Sobrevida , Fatores de TempoRESUMO
OBJECTIVE: To assess whether late surfactant treatment in extremely low gestational age (GA) newborn infants requiring ventilation at 7-14 days, who often have surfactant deficiency and dysfunction, safely improves survival without bronchopulmonary dysplasia (BPD). STUDY DESIGN: Extremely low GA newborn infants (GA ≤28 0/7 weeks) who required mechanical ventilation at 7-14 days were enrolled in a randomized, masked controlled trial at 25 US centers. All infants received inhaled nitric oxide and either surfactant (calfactant/Infasurf) or sham instillation every 1-3 days to a maximum of 5 doses while intubated. The primary outcome was survival at 36 weeks postmenstrual age (PMA) without BPD, as evaluated by physiological oxygen/flow reduction. RESULTS: A total of 511 infants were enrolled between January 2010 and September 2013. There were no differences between the treated and control groups in mean birth weight (701 ± 164 g), GA (25.2 ± 1.2 weeks), percentage born at GA <26 weeks (70.6%), race, sex, severity of lung disease at enrollment, or comorbidities of prematurity. Survival without BPD did not differ between the treated and control groups at 36 weeks PMA (31.3% vs 31.7%; relative benefit, 0.98; 95% CI, 0.75-1.28; P = .89) or 40 weeks PMA (58.7% vs 54.1%; relative benefit, 1.08; 95% CI, 0.92-1.27; P = .33). There were no between-group differences in serious adverse events, comorbidities of prematurity, or severity of lung disease to 36 weeks. CONCLUSION: Late treatment with up to 5 doses of surfactant in ventilated premature infants receiving inhaled nitric oxide was well tolerated, but did not improve survival without BPD at 36 or 40 weeks. Pulmonary and neurodevelopmental assessments are ongoing. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01022580.
Assuntos
Displasia Broncopulmonar/etiologia , Óxido Nítrico/administração & dosagem , Surfactantes Pulmonares/uso terapêutico , Respiração Artificial/efeitos adversos , Administração por Inalação , Displasia Broncopulmonar/epidemiologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/mortalidade , Doenças do Prematuro/terapia , Recém-Nascido de muito Baixo Peso , Masculino , Óxido Nítrico/efeitos adversos , Surfactantes Pulmonares/efeitos adversos , Respiração Artificial/mortalidade , Taxa de Sobrevida , Estados UnidosRESUMO
OBJECTIVES: To determine the prevalence in the neonatal literature of statistical approaches accounting for the unique clustering patterns of multiple births and to explore the sensitivity of an actual trial to several analytic approaches to multiples. STUDY DESIGN: A systematic review of recent perinatal trials assessed the prevalence of studies accounting for clustering of multiples. The Nitric Oxide to Prevent Chronic Lung Disease (NO CLD) trial served as a case study of the sensitivity of the outcome to several statistical strategies. We calculated odds ratios using nonclustered (logistic regression) and clustered (generalized estimating equations, multiple outputation) analyses. RESULTS: In the systematic review, most studies did not describe the random assignment of twins and did not account for clustering. Of those studies that did, exclusion of multiples and generalized estimating equations were the most common strategies. The NO CLD study included 84 infants with a sibling enrolled in the study. Multiples were more likely than singletons to be white and were born to older mothers (P < .01). Analyses that accounted for clustering were statistically significant; analyses assuming independence were not. CONCLUSIONS: The statistical approach to multiples can influence the odds ratio and width of confidence intervals, thereby affecting the interpretation of a study outcome. A minority of perinatal studies address this issue.
Assuntos
Prole de Múltiplos Nascimentos/estatística & dados numéricos , Gravidez Múltipla/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Projetos de Pesquisa/estatística & dados numéricos , Adulto , Viés , Broncodilatadores/uso terapêutico , Displasia Broncopulmonar/prevenção & controle , Análise por Conglomerados , Intervalos de Confiança , Interpretação Estatística de Dados , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Modelos Logísticos , Óxido Nítrico/uso terapêutico , Razão de Chances , Gravidez , Sensibilidade e Especificidade , Análise de SobrevidaRESUMO
OBJECTIVE: To identify whether inhaled nitric oxide treatment decreased indicators of long-term pulmonary morbidities after discharge from the neonatal intensive care unit. STUDY DESIGN: The Nitric Oxide (to Prevent) Chronic Lung Disease trial enrolled preterm infants (<1250 g) between 7 to 21 days of age who were ventilated and at high risk for bronchopulmonary dysplasia. Follow-up occurred at 12 +/- 3 months of age adjusted for prematurity; long-term pulmonary morbidity and other outcomes were reported by parents during structured blinded interviews. RESULTS: A total of 456 infants (85%) were seen at 1 year. Compared with control infants, infants randomized to inhaled nitric oxide received significantly less bronchodilators (odds ratio [OR] 0.53 [95% confidence interval 0.36-0.78]), inhaled steroids (OR 0.50 [0.32-0.77]), systemic steroids (OR 0.56 [0.32-0.97]), diuretics (OR 0.54 [0.34-0.85]), and supplemental oxygen (OR 0.65 [0.44-0.95]) after discharge from the neonatal intensive care unit. There were no significant differences between parental report of rehospitalizations (OR 0.83 [0.57-1.21]) or wheezing or whistling in the chest (OR 0.70 [0.48-1.03]). CONCLUSIONS: Infants treated with inhaled nitric oxide received fewer outpatient respiratory medications than the control group. However, any decision to institute routine use of this dosing regimen should also take into account the results of the 24-month neurodevelopmental assessment.