早期吸入布地奈德预防支气管肺发育不良。

Early Inhaled Budesonide for the Prevention of Bronchopulmonary Dysplasia.

机构信息

From the Department of Neonatology, University Hospital Zurich, University of Zurich, Zurich (D.B.), and the Department of Pediatric Pharmacology, University Children's Hospital, Basel (J.N.A.) - both in Switzerland; the Department of Neonatology (D.B., C.F.P.) and the Center for Pediatric Clinical Studies (C.E.), University Children's Hospital Tübingen, and the Institute for Clinical Epidemiology and Applied Biometry (C.M.) and the Department of Clinical Pharmacology (M.S.), University Hospital Tübingen, Tübingen, and Dr. Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart (M.S.) - all in Germany; Charles University, General University Hospital and First Faculty of Medicine, Prague, Czech Republic (R.P.); Ziv Medical Center, Zefat, Bar-Ilan University, Ramat Gan, Israel (E.S.S.); the Department of Pediatrics, Oulu University Hospital and University of Oulu, Oulu, Finland (M.H.); Assistance Publique-Hôpitaux de Paris, Département Hospitalo-Universitaire, Université Paris Descartes, Hôpital Cochin, Service de Médecine et Réanimation néonatales de Port-Royal, Paris (P.-H.J.); Polytechnic University of Marche, Salesi Children's Hospital, Ancona, Italy (V.C.); the Division of Pediatric Clinical Pharmacology, Children's National Medical Center, Washington, DC (J.N.A.); Intensive Care and Department of Pediatric Surgery, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands (J.N.A.); and the Department of Child Health at Queen's University Belfast, Institute of Clinical Science, Belfast, Northern Ireland (H.L.H.).

出版信息

N Engl J Med. 2015 Oct 15;373(16):1497-506. doi: 10.1056/NEJMoa1501917.

DOI:10.1056/NEJMoa1501917

PMID:26465983

Abstract

BACKGROUND

Systemic glucocorticoids reduce the incidence of bronchopulmonary dysplasia among extremely preterm infants, but they may compromise brain development. The effects of inhaled glucocorticoids on outcomes in these infants are unclear.

METHODS

We randomly assigned 863 infants (gestational age, 23 weeks 0 days to 27 weeks 6 days) to early (within 24 hours after birth) inhaled budesonide or placebo until they no longer required oxygen and positive-pressure support or until they reached a postmenstrual age of 32 weeks 0 days. The primary outcome was death or bronchopulmonary dysplasia, confirmed by means of standardized oxygen-saturation monitoring, at a postmenstrual age of 36 weeks.

RESULTS

A total of 175 of 437 infants assigned to budesonide for whom adequate data were available (40.0%), as compared with 194 of 419 infants assigned to placebo for whom adequate data were available (46.3%), died or had bronchopulmonary dysplasia (relative risk, stratified according to gestational age, 0.86; 95% confidence interval [CI], 0.75 to 1.00; P=0.05). The incidence of bronchopulmonary dysplasia was 27.8% in the budesonide group versus 38.0% in the placebo group (relative risk, stratified according to gestational age, 0.74; 95% CI, 0.60 to 0.91; P=0.004); death occurred in 16.9% and 13.6% of the patients, respectively (relative risk, stratified according to gestational age, 1.24; 95% CI, 0.91 to 1.69; P=0.17). The proportion of infants who required surgical closure of a patent ductus arteriosus was lower in the budesonide group than in the placebo group (relative risk, stratified according to gestational age, 0.55; 95% CI, 0.36 to 0.83; P=0.004), as was the proportion of infants who required reintubation (relative risk, stratified according to gestational age, 0.58; 95% CI, 0.35 to 0.96; P=0.03). Rates of other neonatal illnesses and adverse events were similar in the two groups.

CONCLUSIONS

Among extremely preterm infants, the incidence of bronchopulmonary dysplasia was lower among those who received early inhaled budesonide than among those who received placebo, but the advantage may have been gained at the expense of increased mortality. (Funded by the European Union and Chiesi Farmaceutici; ClinicalTrials.gov number, NCT01035190.).

摘要

背景

全身用糖皮质激素可降低极早产儿支气管肺发育不良的发生率，但可能会损害脑发育。吸入用糖皮质激素对这些婴儿的结局影响尚不清楚。

方法

我们将 863 名（胎龄 23 周零 0 天至 27 周零 6 天）婴儿随机分为早期（出生后 24 小时内）吸入布地奈德或安慰剂组，直至他们不再需要吸氧和正压支持，或达到校正胎龄 32 周零 0 天。主要结局是校正胎龄 36 周时通过标准化氧饱和度监测证实的死亡或支气管肺发育不良。

结果

在布地奈德组，共有 437 名可获得充分数据的婴儿中有 175 名（40.0%），而在可获得充分数据的 419 名安慰剂组婴儿中有 194 名（46.3%）死亡或患有支气管肺发育不良（按胎龄分层的相对风险为 0.86；95%置信区间[CI]为 0.75 至 1.00；P=0.05）。布地奈德组支气管肺发育不良的发生率为 27.8%，安慰剂组为 38.0%（按胎龄分层的相对风险为 0.74；95%CI 为 0.60 至 0.91；P=0.004）；分别有 16.9%和 13.6%的患儿死亡（按胎龄分层的相对风险为 1.24；95%CI 为 0.91 至 1.69；P=0.17）。与安慰剂组相比，布地奈德组需要手术关闭动脉导管未闭的患儿比例较低（按胎龄分层的相对风险为 0.55；95%CI 为 0.36 至 0.83；P=0.004），需要再次插管的患儿比例也较低（按胎龄分层的相对风险为 0.58；95%CI 为 0.35 至 0.96；P=0.03）。两组间其他新生儿疾病和不良事件的发生率相似。