Assuntos
Displasia Broncopulmonar , Etnicidade , Humanos , Recém-Nascido , Óxido Nítrico , Grupos RaciaisRESUMO
OBJECTIVE: To evaluate the relationship between maternal self-reported race/ethnicity and persistent wheezing illness in former high-risk, extremely low gestational age newborns, and to quantify the contribution of socioeconomic, environmental, and biological factors on this relationship. STUDY DESIGN: We assessed persistent wheezing illness determined at 18-24 months corrected (for prematurity) age in survivors of a randomized trial. Parents/caregivers were surveyed for wheeze and inhaled asthma medication use quarterly to 12 months, and at 18 and 24 months. We used multivariable analysis to evaluate the relationship of maternal race to persistent wheezing illness, and identified mediators for this relationship via formal mediation analysis. RESULTS: Of 420 infants (25.2 ± 1.2 weeks of gestation and 714 ± 166 g at birth, 57% male, 34% maternal black race), 189 (45%) had persistent wheezing illness. After adjustment for gestational age, birth weight, and sex, infants of black mothers had increased odds of persistent wheeze compared with infants of nonblack mothers (OR = 2.9, 95% CI 1.9, 4.5). Only bronchopulmonary dysplasia, breast milk diet, and public insurance status were identified as mediators. In this model, the direct effect of race accounted for 69% of the relationship between maternal race and persistent wheeze, whereas breast milk diet, public insurance status, and bronchopulmonary dysplasia accounted for 8%, 12%, and 10%, respectively. CONCLUSIONS: Among former high-risk extremely low gestational age newborns, infants of black mothers have increased odds of developing persistent wheeze. A substantial proportion of this effect is directly accounted for by race, which may reflect unmeasured environmental influences, and acquired and innate biological differences. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01022580.
Assuntos
Negro ou Afro-Americano , Doenças do Prematuro/etnologia , Mães , Sons Respiratórios/etiologia , Pré-Escolar , Feminino , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Doenças do Prematuro/terapia , Masculino , Respiração Artificial , Fatores de RiscoRESUMO
OBJECTIVE: To assess whether inhaled nitric oxide (iNO) improves survival without bronchopulmonary dysplasia (BPD) for preterm African American infants. STUDY DESIGN: An individual participant data meta-analysis was conducted, including 3 randomized, placebo-controlled trials that enrolled infants born at <34 weeks of gestation receiving respiratory support, had at least 15% (or a minimum of 10 infants in each trial arm) of African American race, and used a starting iNO of >5 parts per million with the intention to treat for 7 days minimum. The primary outcome was a composite of death or BPD. Secondary outcomes included death before discharge, postnatal steroid use, gross pulmonary air leak, pulmonary hemorrhage, measures of respiratory support, and duration of hospital stay. RESULTS: Compared with other races, African American infants had a significant reduction in the composite outcome of death or BPD with iNO treatment: 49% treated vs 63% controls (relative risk, 0.77; 95% CI, 0.65-0.91; P = .003; interaction P = .016). There were no differences between racial groups for death. There was also a significant difference between races (interaction P = .023) of iNO treatment for BPD in survivors, with the greatest effect in African American infants (P = .005). There was no difference between racial groups in the use of postnatal steroids, pulmonary air leak, pulmonary hemorrhage, or other measures of respiratory support. CONCLUSION: iNO therapy should be considered for preterm African American infants at high risk for BPD. iNO to prevent BPD in African Americans may represent an example of a racially customized therapy for infants.
Assuntos
Displasia Broncopulmonar/etnologia , Mortalidade Infantil/etnologia , Óxido Nítrico/administração & dosagem , Administração por Inalação , Negro ou Afro-Americano/estatística & dados numéricos , Displasia Broncopulmonar/prevenção & controle , Glucocorticoides/administração & dosagem , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Tempo de Internação/estatística & dados numéricos , Óxido Nítrico/efeitos adversos , Fatores Raciais , Terapia Respiratória/efeitos adversos , Terapia Respiratória/estatística & dados numéricos , Taxa de SobrevidaAssuntos
Displasia Broncopulmonar/tratamento farmacológico , Desenvolvimento de Medicamentos/métodos , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Doenças do Recém-Nascido/tratamento farmacológico , Recém-Nascido Prematuro , Inflamação , Masculino , Pediatria/métodos , Pediatria/tendências , Gravidez , Complicações na Gravidez , Fatores de Risco , FumarRESUMO
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 the prognostic accuracy of early cumulative supplemental oxygen (CSO) exposure for prediction of bronchopulmonary dysplasia (BPD) or death, and to evaluate the independent association of CSO with BPD or death. STUDY DESIGN: We performed a secondary analysis of the Trial of Late Surfactant, which enrolled 511 infants born at ≤28 weeks gestational age who were mechanically ventilated at 7-14 days of life. Our primary outcome was BPD or death at 36 weeks postmenstrual age, as determined by a physiological oxygen/flow challenge. Average daily supplemental oxygen (fraction of inspired oxygen - 0.21) was calculated. CSO was calculated as the sum of the average daily supplemental oxygen over time periods of interest up to 28 days of age. Area under the receiver operating curve (AUROC) values were generated to evaluate the accuracy of CSO for prediction of BPD or death. The independent relationship between CSO and BPD or death was assessed in multivariate modeling, while adjusting for mean airway pressure. RESULTS: In the study infants, mean gestational age at birth was 25.2 ± 1.2 weeks and mean birth weight was 700 ± 165 g. The AUROC value for CSO at 14 days was significantly better than that at earlier time points for outcome prediction (OR, 0.70; 95% CI, 0.65-0.74); it did not increase with the addition of later data. In multivariate modeling, a CSO increase of 1 at 14 days increased the odds of BPD or death (OR, 1.7; 95% CI, 1.3-2.2; P < .0001), which corresponds to a 7% higher daily supplemental oxygen value. CONCLUSION: In high-risk extremely low gestational age newborns, the predictive accuracy of CSO plateaus at 14 days. CSO is independently associated with BPD or death. This index may identify infants who could benefit from early intervention to prevent BPD.
Assuntos
Displasia Broncopulmonar/diagnóstico , Oxigenoterapia/métodos , Displasia Broncopulmonar/mortalidade , Displasia Broncopulmonar/fisiopatologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Estudos Prospectivos , Curva ROC , Risco , Taxa de SobrevidaRESUMO
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
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.
Assuntos
Pneumopatias/epidemiologia , Pneumopatias/prevenção & controle , Óxido Nítrico/administração & dosagem , Administração por Inalação , Doença Crônica , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Unidades de Terapia Intensiva Neonatal , Pneumopatias/tratamento farmacológico , Readmissão do Paciente/estatística & dados numéricos , Sons Respiratórios , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate whether therapeutic hypothermia alters the prognostic value of clinical grading of neonatal encephalopathy. STUDY DESIGN: This study was a secondary analysis of a multicenter study of 234 term infants with neonatal encephalopathy randomized to head cooling for 72 hours starting within 6 hours of birth, with rectal temperature maintained at 34.5 degrees C +/- 0.5 degrees C, followed by re-warming for 4 hours, or standard care at 37.0 degrees C +/- 0.5 degrees C. Severity of encephalopathy was measured pre-randomization and on day 4, after re-warming, in 177 infants; 31 infants died before day 4, and data were missing for 10 infants. The primary outcome was death or severe disability at 18 months of age. RESULTS: Milder pre-randomization encephalopathy, greater improvement in encephalopathy from randomization to day 4, and cooling were associated with favorable outcome in multivariate binary logistic regression. Hypothermia did not affect severity of encephalopathy at day 4, however, in infants with moderate encephalopathy at day 4, those treated with hypothermia had a significantly higher rate of favorable outcome (31/45 infants, 69%, P = .006) compared with standard care (12/33, 36%). CONCLUSION: Infants with moderate encephalopathy on day 4 may have a more favorable prognosis after hypothermia treatment than expected after standard care.
Assuntos
Hipotermia Induzida , Hipóxia-Isquemia Encefálica/terapia , Feminino , Humanos , Recém-Nascido , Modelos Logísticos , Masculino , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
OBJECTIVES: To explore how fear of litigation influences neonatal treatment decisions. STUDY DESIGN: In a mailed survey, we presented a hypothetical vignette of a premature infant to 1000 neonatologists. We asked them to estimate prognosis, indicate appropriate intervention, and respond to parental treatment requests. Subjects were randomly assigned to receive one of two questionnaires, "litigious" or "nonlitigious," which differed only in the description of the infant's parents. RESULTS: The response rate was 63.0%. The vast majority of respondents deferred to parental requests rather than adhering to their best judgment. They deferred whether or not parents requested treatment and whether or not parents were described as litigious (P <.0001). Among those respondents who shifted their resuscitation opinion after parental introduction, respondents to the nonlitigious version were more likely to shift their opinion from "treat" to "do not treat" after parental requests to "use your best judgment" (P <.042). The influence of parental litigiousness was primarily seen among neonatologists who thought that the infant's prognosis was dismal (P <.044). CONCLUSIONS: There is a strong disposition among neonatologists toward respecting parental wishes. This disposition is stronger when neonatologists are given additional reason to be concerned about litigation.