RESUMO
OBJECTIVE: In a randomized multi-center trial, we demonstrated that inhaled nitric oxide begun between 7 and 21 days and given for 24 days significantly increased survival without bronchopulmonary dysplasia (BPD) in ventilated premature infants weighing <1250 g. Because some preventative BPD treatments are associated with neurodevelopmental impairment, we designed a follow-up study to assess the safety of nitric oxide. STUDY DESIGN: Our hypothesis was that inhaled nitric oxide would not increase neurodevelopmental impairment compared with placebo. We prospectively evaluated neurodevelopmental and growth outcomes at 24 months postmenstrual age in 477 of 535 surviving infants (89%) enrolled in the trial. RESULTS: In the treated group, 109 of 243 children (45%) had neurodevelopmental impairment (moderate or severe cerebral palsy, bilateral blindness, bilateral hearing loss, or score <70 on the Bayley Scales II), compared with 114 of 234 (49%) in the placebo group (relative risk, 0.92; 95% CI, 0.75-1.12; P = .39). No differences on any subcomponent of neurodevelopmental impairment or growth variables were found between inhaled nitric oxide or placebo. CONCLUSIONS: Inhaled nitric oxide improved survival free of BPD, with no adverse neurodevelopmental effects at 2 years of age.
Assuntos
Displasia Broncopulmonar/prevenção & controle , Deficiências do Desenvolvimento/prevenção & controle , Sequestradores de Radicais Livres/administração & dosagem , Recém-Nascido Prematuro , Óxido Nítrico/administração & dosagem , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Administração por Inalação , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/etiologia , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/etiologia , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Síndrome do Desconforto Respiratório do Recém-Nascido/complicações , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
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.