Department of Neonatology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Department of Neonatology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
JAMA. 2019 Jan 29;321(4):354-363. doi: 10.1001/jama.2018.21443.
Dexamethasone initiated after the first week of life reduces the rate of death or bronchopulmonary dysplasia (BPD) but may cause long-term adverse effects in very preterm infants. Hydrocortisone is increasingly used as an alternative, but evidence supporting its efficacy and safety is lacking.
To assess the effect of hydrocortisone initiated between 7 and 14 days after birth on death or BPD in very preterm infants.
DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled randomized trial conducted in 19 neonatal intensive care units in the Netherlands and Belgium from November 15, 2011, to December 23, 2016, among preterm infants with a gestational age of less than 30 weeks and/or birth weight of less than 1250 g who were ventilator dependent between 7 and 14 days of life, with follow-up to hospital discharge ending December 12, 2017.
Infants were randomly assigned to receive a 22-day course of systemic hydrocortisone (cumulative dose, 72.5 mg/kg) (n = 182) or placebo (n = 190).
The primary outcome was a composite of death or BPD assessed at 36 weeks' postmenstrual age. Twenty-nine secondary outcomes were analyzed up to hospital discharge, including death and BPD at 36 weeks' postmenstrual age.
Among 372 patients randomized (mean gestational age, 26 weeks; 55% male), 371 completed the trial; parents withdrew consent for 1 child treated with hydrocortisone. Death or BPD occurred in 128 of 181 infants (70.7%) randomized to hydrocortisone and in 140 of 190 infants (73.7%) randomized to placebo (adjusted risk difference, -3.6% [95% CI, -12.7% to 5.4%]; adjusted odds ratio, 0.87 [95% CI, 0.54-1.38]; P = .54). Of 29 secondary outcomes, 8 showed significant differences, including death at 36 weeks' postmenstrual age (15.5% with hydrocortisone vs 23.7% with placebo; risk difference, -8.2% [95% CI, -16.2% to -0.1%]; odds ratio, 0.59 [95% CI, 0.35-0.995]; P = .048). Twenty-one outcomes showed nonsignificant differences, including BPD (55.2% with hydrocortisone vs 50.0% with placebo; risk difference, 5.2% [95% CI, -4.9% to 15.2%]; odds ratio, 1.24 [95% CI, 0.82-1.86]; P = .31). Hyperglycemia requiring insulin therapy was the only adverse effect reported more often in the hydrocortisone group (18.2%) than in the placebo group (7.9%).
Among mechanically ventilated very preterm infants, administration of hydrocortisone between 7 and 14 days after birth, compared with placebo, did not improve the composite outcome of death or BPD at 36 weeks' postmenstrual age. These findings do not support the use of hydrocortisone for this indication.
Netherlands National Trial Register Identifier: NTR2768.
在生命的第一周后开始使用地塞米松可以降低死亡率或支气管肺发育不良（BPD）的发生率，但可能会对极早产儿产生长期不良影响。氢化可的松作为替代药物越来越多地被使用，但缺乏支持其疗效和安全性的证据。
评估在出生后 7 至 14 天开始使用氢化可的松对极早产儿死亡或 BPD 的影响。
设计、地点和参与者：这是一项在荷兰和比利时的 19 家新生儿重症监护病房进行的双盲、安慰剂对照随机试验，纳入了胎龄小于 30 周且/或出生体重小于 1250 克、在生命的第 7 至 14 天期间需要呼吸机支持且依赖呼吸机的早产儿，随访至出院，最终随访时间为 2017 年 12 月 12 日。
婴儿被随机分配接受为期 22 天的全身氢化可的松治疗（累积剂量 72.5mg/kg）（n=182）或安慰剂（n=190）。
主要结局是在出生后 36 周时评估的死亡或 BPD 复合结局。分析了 29 个次要结局，包括在出生后 36 周时的死亡和 BPD。
在 372 名随机分组的患者中（平均胎龄 26 周；55%为男性），371 名患者完成了试验；1 名接受氢化可的松治疗的婴儿的父母撤回了同意。181 名接受氢化可的松治疗的婴儿中有 128 名（70.7%）和 190 名接受安慰剂治疗的婴儿中有 140 名（73.7%）发生死亡或 BPD（调整风险差异，-3.6%[95%CI，-12.7%至 5.4%]；调整后的比值比，0.87[95%CI，0.54-1.38]；P=0.54）。29 个次要结局中有 8 个存在显著差异，包括在出生后 36 周时的死亡率（接受氢化可的松治疗的婴儿为 15.5%，接受安慰剂治疗的婴儿为 23.7%；风险差异，-8.2%[95%CI，-16.2%至-0.1%]；比值比，0.59[95%CI，0.35-0.995]；P=0.048）。21 个结局显示无显著差异，包括 BPD（接受氢化可的松治疗的婴儿为 55.2%，接受安慰剂治疗的婴儿为 50.0%；风险差异，5.2%[95%CI，-4.9%至 15.2%]；比值比，1.24[95%CI，0.82-1.86]；P=0.31）。需要胰岛素治疗的高血糖是氢化可的松组（18.2%）比安慰剂组（7.9%）更常见的唯一不良反应。
在机械通气的极早产儿中，与安慰剂相比，在出生后 7 至 14 天开始使用氢化可的松并未改善出生后 36 周时的死亡或 BPD 复合结局。这些发现不支持将氢化可的松用于该适应症。
荷兰国家试验注册中心编号：NTR2768。
