Shah V, Ohlsson A, Halliday H L, Dunn M S
Mount Sinai Hospital, Department of Paediatrics, Room 775A, 600 University Avenue, Toronto, Ontario, Canada, M5G 1X5.
Cochrane Database Syst Rev. 2007 Oct 17(4):CD001969. doi: 10.1002/14651858.CD001969.pub2.
BACKGROUND: Chronic lung disease remains a common complication among preterm infants. There is increasing evidence that inflammation plays an important role in the pathogenesis of CLD. Due to their strong anti-inflammatory properties, corticosteroids are an attractive intervention strategy. However, there are growing concerns regarding short and long-term effects of systemic corticosteroids. Theoretically, administration of inhaled corticosteroids may allow for beneficial effects on the pulmonary system with a lower risk of undesirable systemic side effects. OBJECTIVES: To determine the impact of inhaled corticosteroids administered to ventilated very low birth weight preterm neonates in the first two weeks of life for the prevention of chronic lung disease (CLD). SEARCH STRATEGY: Randomized and quasi-randomized trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2007), MEDLINE (1966 - July 2007), EMBASE (1980 - July 2007), CINAHL (1982 - July 2007), reference lists of published trials and abstracts published in Pediatric Research or electronically on the Pediatric Academic Societies web-site (1990 - April 2007). SELECTION CRITERIA: Randomized controlled trials of inhaled corticosteroid therapy initiated within the first 2 weeks of life in ventilated preterm infants with birth weight <1500 grams were included in this review. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including chronic lung disease at 28 days or 36 weeks postmenstrual age (PMA), mortality, combined outcome of death or CLD at 28 days of age and at 36 weeks PMA, the need for systemic corticosteroids, failure to extubate within 14 days and adverse effects of corticosteroids were evaluated. All data were analyzed using RevMan 4.2.10. When possible, meta-analysis was performed using relative risk (RR), risk difference (RD), along with their 95% confidence intervals (CI). If RD was significant, the number needed to treat (NNT) was calculated. MAIN RESULTS: Three additional trials were identified for inclusion in this update. Eleven trials assessing the impact of inhaled corticosteroid for the prevention of CLD were identified. Four trials were excluded. The present review includes data analyses based on seven qualifying trials. There was no statistically significant effect of inhaled steroids on CLD either at 28 days [typical RR 1.05 (95% CI 0.84, 1.32); typical RD 0.02 (95% CO -0.07, 0.11)] or at 36 weeks PMA [typical RR 0.97 (95% CI 0.62, 1.52); typical RD 0.00 (95% CI -0.07, 0.06)], when analyzed either for all randomized infants or among survivors. No statistically significant differences were noted for mortality or for the combined outcome of mortality and CLD either at 28 days of age or at 36 weeks PMA. There were no statistically significant differences in adverse events between groups. AUTHORS' CONCLUSIONS: Based on this updated review, there is no evidence from the trials reviewed that early administration (in the first two weeks of life) of inhaled steroids to ventilated preterm neonates was effective in reducing the incidence of CLD. Currently, use of inhaled steroids in this population cannot be recommended. Studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for the administration of these medications. Studies need to address both the short-term and long-term benefits and adverse effects of inhaled steroids with particular attention to neurodevelopmental outcome.
背景:慢性肺部疾病仍是早产儿常见的并发症。越来越多的证据表明,炎症在慢性肺部疾病的发病机制中起重要作用。由于具有强大的抗炎特性,皮质类固醇是一种有吸引力的干预策略。然而,人们对全身性皮质类固醇的短期和长期影响越来越担忧。从理论上讲,吸入皮质类固醇可能对肺部系统产生有益作用,同时产生不良全身副作用的风险较低。 目的:确定在出生后两周内对机械通气的极低出生体重早产儿使用吸入皮质类固醇预防慢性肺部疾病(CLD)的效果。 检索策略:通过检索Cochrane对照试验中心注册库(CENTRAL,Cochrane图书馆,2007年第3期)、MEDLINE(1966年至2007年7月)、EMBASE(1980年至2007年7月)、CINAHL(1982年至2007年7月)、已发表试验的参考文献列表以及发表在《儿科研究》上或在儿科学术协会网站上以电子方式发表的摘要(1990年至2007年4月),识别随机和半随机试验。 选择标准:本综述纳入了出生体重<1500克的机械通气早产儿在出生后2周内开始吸入皮质类固醇治疗的随机对照试验。 数据收集与分析:评估了包括28天或孕龄36周时的慢性肺部疾病、死亡率、28天龄和孕龄36周时死亡或慢性肺部疾病的综合结局、全身性皮质类固醇的使用需求、14天内未能拔管以及皮质类固醇的不良反应等临床结局数据。所有数据使用RevMan 4.2.10进行分析。尽可能使用相对风险(RR)、风险差(RD)及其95%置信区间(CI)进行荟萃分析。如果RD显著,则计算治疗所需人数(NNT)。 主要结果:本次更新又确定了三项试验纳入。共识别出11项评估吸入皮质类固醇预防慢性肺部疾病效果的试验。排除了4项试验。本综述包括基于7项符合条件试验的数据分析。对于所有随机分组的婴儿或幸存者进行分析时,吸入类固醇在28天时[典型RR 1.05(95%CI 0.84,1.32);典型RD 0.02(95%CI -0.07,0.11)]或孕龄36周时[典型RR 0.97(95%CI 0.62,1.52);典型RD 0.00(95%CI -0.07,0.06)]对慢性肺部疾病均无统计学显著影响。在28天龄或孕龄36周时,死亡率或死亡与慢性肺部疾病的综合结局均无统计学显著差异。两组间不良事件无统计学显著差异。 作者结论:基于本次更新的综述,在所审查的试验中没有证据表明对机械通气的早产儿在出生后早期(出生后两周内)使用吸入类固醇可有效降低慢性肺部疾病的发生率。目前,不建议在该人群中使用吸入类固醇。需要开展研究以确定这些药物不同给药技术和给药方案的风险/效益比。研究需要关注吸入类固醇的短期和长期益处及不良反应,尤其要关注神经发育结局。
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