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Alpha-1 proteinase inhibitor (a1PI) for preventing chronic lung disease in preterm infants

  • Review
  • Intervention

Authors

  • Prakeshkumar S Shah,

    Corresponding author
    1. University of Toronto, Department of Paediatrics and Department of Health Policy, Management and Evaluation, Rm 775A, Toronto, Ontario, Canada
    • Prakeshkumar S Shah, Department of Paediatrics and Department of Health Policy, Management and Evaluation, Rm 775A, University of Toronto, 600 University Avenue, Toronto, Ontario, M5G 1XB, Canada. pshah@mtsinai.on.ca.

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  • Arne Ohlsson

    1. University of Toronto, Departments of Paediatrics, Obstetrics and Gynaecology and Health Policy, Management and Evaluation, Toronto, Ontario, Canada
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Abstract

Background

Inflammation of the pulmonary parenchyma is one of the important mechanisms implicated in development of chronic lung disease (CLD) in preterm neonates.

Objectives

To evaluate the effect of alpha 1 proteinase inhibitor (a1PI) for the prevention of chronic lung disease (CLD) in preterm neonates.

Search methods

We searched the following databases: MEDLINE (1966 to February 2005), EMBASE (1980 to February 2005), CINAHL (1982 to February 2005), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2005) and abstracts from the annual meetings of the Society of Pediatric Research, American Pediatric Society and Pediatric Academic Societies published in Pediatric Research (1991 to 2004). No language restrictions were applied.

The electronic search was updated in 2010.

Selection criteria

Randomised or quasi-randomised trials of administration of a1PI compared to placebo or no treatment within the first week of life in preterm neonates.

Data collection and analysis

Data collection and analysis was performed in accordance with the methods of the Cochrane Neonatal Review Group.

Main results

Two eligible studies were identified. The methodological qualities of identified studies were good. One study randomised infants to either placebo or a1PI 60 mg/kg/dose for four doses while in the second study the same investigators explored the efficacy of different dose regimens of a1PI compared to placebo. There was no statistically significant difference in the risk of developing CLD at 36 weeks postmenstrual age among all randomised infants at any dose of a1PI (pooled RR 0.79, 95% CI 0.44 to 1.41) or when given 60 mg/kg/dose for four doses compared to placebo (pooled RR 0.64, 95% CI 0.35 to 1.18).

There was a trend towards reduced risk of development of oxygen dependency at 28 days postnatal age for 60 mg/kg/dose for four doses of a1PI compared to placebo. When any doses of a1PI were combined, the pooled RR was statistically significant [RR 0.80 (95% CI 0.65 to 0.98); RD -0.15 (95 % CI -0.29 to -0.01)].

Treatment with a1PI did not reduce the risk of CLD and/or death at 36 weeks postmenstrual age or the risk of long term neurodevelopmental abnormalities. In addition, no statistically significant difference was noted in other respiratory parameters such as duration of oxygen requirement or respiratory support.

Authors' conclusions

Prophylactic administration of a1PI did not reduce the risk of CLD at 36 weeks or long term adverse developmental outcomes in preterm neonates.

摘要

背景

α−1蛋白?抑製劑(a1PI)預防早產兒慢性肺部疾病

肺實質炎症是早產新生兒慢性肺部疾病(慢性肺疾,CLD)的重要發病機制之一。細胞損傷後釋放的?和其它抗氧化劑被認為是肺組織損傷的原因。人們嘗試了各種方法來抵消?對肺實質的傷害和預防慢性肺疾。

目標

本評價評估α−1蛋白?抑製劑(a1PI)對預防早產兒到達懷孕週數36週時慢性肺疾(CLD)(根據補氧需要量定義)的效果。

搜尋策略

文獻檢索使用了以下數據庫: MEDLINE (1966年 2005年2月)、EMBASE (1980年 2005年2月)、CINAHL (1982年 2005年2月)、Cochrane對照試驗中心註冊資料庫(CENTRAL, Cochrane圖書館,2005年第1期)和發表在“兒科研究”上的兒科研究學會、美國兒科學會和兒科學術學會的年會摘要(1991年-2004年)。文獻檢索未設語種限制。

選擇標準

應用於臨床試驗的選擇標準: 1. 必須是早產新生兒群體。 2. 干預方式必須是在出生後第1週內,應用a1PI 與安慰劑或不治療進行比較。 3. 合格研究必須包含以下任何結局: a. 慢性肺疾的預防b. 輔助通氣時間的減少c. 氧氣需求時間的減少d. 全身性抗炎治療需要的減少e. 死亡率減少或f. 遠期不良神經後遺症減少。 4. 必須是隨機或半隨機試驗。

資料收集與分析

利用研究中和通過與作者個人通信提供的信息評估試驗的方法學質量。提取相關結局的數據,估算效果的程度,視情況以匯總相對危險度(RR)、風險差(RD)和加權均數差(WMD)報告結果。使用了兩種方法進行分析: 1. 在出生後前兩週,a1PI 以劑量60毫克/公斤,用藥4天與安慰劑比較,以及2. 在出生後前二週,任何劑量a1PI 用藥與安慰劑比較。

主要結論

確定了二項合格研究。這些研究的方法學質量良好。一項研究將嬰兒隨機分到安慰劑,或a1PI 每次60 毫克/公斤,用藥4次,而在第二項研究中相同研究者對不同a1PI 劑量方案與安慰劑進行比較。所有隨機分配嬰兒中,早產兒到達懷孕週數36週時,慢性肺疾的發生無統計學意義差異。在a1PI劑量為每次60毫克/公斤,用藥4次與安慰劑的比較中,合併RR 為0.64 [95% CI 0.35, 1.18] 和RD −0.10 [95% CI −0.23, 0.03] ,而任何劑量a1PI 的比較中,RR 0.79 [95% CI 0.44, 1.41],RD −0.05 [95% CI −0.17, 0.06]。

作者結論

a1PI 的預防性用藥不減少早產兒到達懷孕週數36週時慢性肺疾的風險或遠期不良發育結局。

翻譯人

本摘要由臺中榮民總醫院薛榮華翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

沒有足夠的證據表明,長期使用α 1蛋白?抑製劑對早產兒慢性肺疾病的效果。肺部發炎是嬰兒出生早於37週前慢性肺疾病(CLD)其中一個原因。CLD嬰兒需要更多的氧氣並且其也可能導致嚴重的長期問題。肺損害是因釋放?和其他抗氧化劑造成,因為CLD嬰兒具有較低濃度的α 1蛋白?抑製劑(a1P1),這是一種可停止肺組織被破壞的物質。一種AlP1的藥物形式有時會給予來保護他們的肺部。本次試驗回顧發現,沒有足夠的證據顯示a1P1的長期效果。還需要更多的研究。

Plain language summary

Alpha-1 proteinase inhibitor (a1PI) for preventing chronic lung disease in preterm infants

There is not enough evidence to show the long term effect of using Alpha-1 proteinase inhibitor for chronic lung disease in premature babies. Inflammation of the lungs is one of the causes of chronic lung disease (CLD) in babies born before 37 weeks. Babies with CLD need extra oxygen and the disease can also cause serious long-term problems. Lung damage is caused by the release of enzymes and other anti-oxidants because babies with CLD have a low level of Alpha-1 proteinase inhibitor (a1P1), a substance that stops lung tissue being destroyed. A medication version of AlP1 is sometimes given to protect their lungs. The review of the trials found that there is not enough evidence to show long term beneficial effects of a1P1. More research is needed.

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