Importance Bronchopulmonary dysplasia (BPD) is a common adverse outcome in extremely preterm infants born at less than 28 weeks' gestation. Systemic corticosteroids are effective against BPD but may be associated with adverse outcomes. Corticosteroids given directly into the lungs may be effective and safer. Objective To investigate the effectiveness of early intratracheal corticosteroid administration on survival free of BPD in extremely preterm infants. Design, Setting, and Participants Double-blind randomized clinical trial conducted in 21 neonatal units in 4 countries (Australia, New Zealand, Canada, and Singapore), enrolling infants born at less than 28 weeks' gestation and less than 48 hours old who were mechanically ventilated (regardless of ventilator settings or oxygen requirements) or who were receiving noninvasive respiratory support and had a clinical decision to treat with surfactant. Recruitment occurred from January 2018 to March 2023. The last participant was discharged from the hospital in August 2023. Interventions Infants were randomly allocated (1:1) to receive budesonide, 0.25 mg/kg, mixed with surfactant (poractant alfa), administered via an endotracheal tube or thin catheter, or surfactant only. Main Outcomes and Measures The primary outcome was survival free of BPD at 36 weeks' postmenstrual age. There were 15 secondary outcomes, including the 2 components of the primary outcome (survival at 36 weeks and BPD among survivors), and 9 predefined safety outcomes (adverse events). Results The primary analysis included 1059 infants, 524 in the budesonide and surfactant group and 535 in the surfactant-only group. Overall, infants had a mean gestational age of 25.6 weeks (SD, 1.3 weeks) and a mean birth weight of 775 g (SD, 197 g); 586 (55.3%) were male. Survival free of BPD occurred in 134 infants (25.6%) in the budesonide and surfactant group and 121 infants (22.6%) in the surfactant-only group (adjusted risk difference, 2.7% [95% CI, -2.1% to 7.4%]). At 36 weeks' postmenstrual age, 83.2% of infants were alive in the budesonide and surfactant group and 80.6% in the surfactant-only group. Of these, 69.3% and 71.9% were diagnosed with BPD, respectively. Conclusions and Relevance In extremely preterm infants receiving surfactant for respiratory distress syndrome, early intratracheal budesonide may have little to no effect on survival free of BPD. Trial Registration anzctr.org.au Identifier: ACTRN12617000322336.

中文翻译：

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气管内布地奈德与表面活性剂混合治疗极早产儿：PLUSS 随机临床试验。


重要性支气管肺发育不良 （BPD） 是妊娠 28 周以下出生的极早产儿的常见不良结局。全身性皮质类固醇对 BPD 有效，但可能与不良结局有关。直接注射到肺部的皮质类固醇可能更有效且更安全。目的 探讨早期气管内皮质类固醇给药对极早产儿无 BPD 生存率的影响。设计、环境和参与者 在 4 个国家（澳大利亚、新西兰、加拿大和新加坡）的 21 个新生儿病房进行的双盲随机临床试验，招募了妊娠 28 周以下和 48 小时以下出生的婴儿，这些婴儿接受了机械通气（无论呼吸机设置或氧气需求如何）或正在接受无创呼吸支持，并且临床决定使用表面活性剂治疗。招聘于 2018 年 1 月至 2023 年 3 月进行。最后一名参与者于 2023 年 8 月出院。干预 婴儿被随机分配 （1：1） 接受布地奈德 0.25 mg/kg，与表面活性剂 （poractant alfa） 混合，通过气管插管或细导管给药，或仅接受表面活性剂给药。主要结局和措施 主要结局是胎龄 36 周时无 BPD 的生存率。有 15 个次要结局，包括主要结局的 2 个组成部分 （36 周生存率和幸存者的 BPD） 和 9 个预定义的安全结局 （不良事件）。结果 初步分析包括 1059 例婴儿，其中布地奈德和表面活性剂组 524 例，纯表面活性剂组 535 例。总体而言，婴儿的平均胎龄为 25.6 周 （SD， 1.3 周），平均出生体重为 775 g （SD， 197 g）;586 例 （55.3%） 为男性。 布地奈德和表面活性剂组有 134 名婴儿 （25.6%） 无 BPD 的生存率，纯表面活性剂组有 121 名婴儿 （22.6%） （校正风险差，2.7% [95% CI，-2.1% 至 7.4%]）。在胎龄 36 周时，布地奈德和表面活性剂组有 83.2% 的婴儿存活，仅用表面活性剂组有 80.6% 的婴儿存活。其中，69.3% 和 71.9% 分别被诊断出患有 BPD。结论和相关性 在接受表面活性剂治疗呼吸窘迫综合征的极早产儿中，早期气管内布地奈德可能对无 BPD 的生存几乎没有影响。试验注册 anzctr.org.au 标识符： ACTRN12617000322336.