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Late (>7 days) postnatal corticosteroids for chronic lung disease in preterm infants

  • Review
  • Intervention

Authors


Abstract

Background

Many preterm infants who survive go on to develop chronic lung disease (CLD). This is true in infants who have had respiratory distress syndrome (RDS) and in infants without RDS. This is probably due to persistence of inflammation in the lung. Corticosteroids have powerful anti-inflammatory effects and have been used to treat established CLD. However, it is unclear whether any beneficial effects outweigh the adverse effects of these drugs.

Objectives

To determine the effect of late (> 7 days) postnatal corticosteroid treatment compared to control (placebo or nothing) in the preterm infant with CLD.

Search methods

Randomised controlled trials of postnatal corticosteroid therapy were sought from the Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE 1966 through May 2008, hand searching paediatric and perinatal journals, examining previous review articles and information received from practising neonatologists. When possible, authors of all studies were contacted to confirm details of reported follow-up studies or to obtain any information about long-term follow-up where none had been reported.

Selection criteria

Randomised controlled trials (RCTs) of postnatal corticosteroid treatment initiated after seven days after birth in preterm infants with or developing CLD were selected for this review.

Data collection and analysis

Data regarding clinical outcomes including mortality, CLD (including need for home oxygen, or need for late rescue with corticosteroids), death or CLD, failure to extubate, complications in the primary hospitalisation (including infection, hyperglycaemia, glycosuria, hypertension, echodensities on ultrasound scan of brain, necrotising enterocolitis (NEC), gastrointestinal (GI) bleeding, GI perforation, intraventricular hemorrhage (IVH), severe retinopathy of prematurity (ROP), and long-term outcomes (including blindness, deafness, cerebral palsy and major neurosensory disability), were abstracted and analysed using RevMan 5

Main results

Nineteen RCTs enrolling a total of 1345 participants were eligible for this review. Late steroid treatment was associated with a reduction in neonatal mortality (at 28 days) but not mortality at discharge or latest reported age. Beneficial effects of delayed steroid treatment included reductions in failure to extubate by 3, 7 or 28 days, CLD at both 28 days and 36 weeks' postmenstrual age (overall and in survivors), need for late rescue treatment with dexamethasone, discharge to home on oxygen therapy, and death or CLD at both 28 days and 36 weeks' postmenstrual age (PMA). There was a trend towards an increase in risk of infection and GI bleeding but not NEC. Short-term adverse affects included hyperglycaemia, glycosuria and hypertension. There was an increase in severe ROP (overall and a trend in survivors) but no significant increase in blindness. There was trend towards a reduction in severe IVH but only 247 infants were enrolled in five studies reporting this outcome. The trends to an increase in cerebral palsy or abnormal neurological examination were partly offset by a trend in the opposite direction in death before late follow-up. The combined rate of death or cerebral palsy was not significantly different between steroid and control groups. Major neurosensory disability, and the combined rate of death or major neurosensory disability, were not significantly different between steroid and control groups. There were no substantial differences between groups for other outcomes in later childhood, including respiratory health or function, blood pressure, or growth.

Authors' conclusions

The benefits of late corticosteroid therapy may not outweigh actual or potential adverse effects. Although there continues to be concern about an increased incidence of adverse neurological outcomes in infants treated with postnatal steroids (see also review of "Early postnatal corticosteroids for preventing chronic lung disease in preterm infants"), this review of postnatal corticosteroid treatment for CLD initiated after seven days of age suggests that late therapy may reduce neonatal mortality without significantly increasing the risk of adverse long-term neurodevelopmental outcomes. However, the methodological quality of the studies determining the long-term outcome is limited in some cases; in some studies the surviving children have only been assessed before school age when some important neurological outcomes cannot be determined with certainty, and no study was sufficiently powered to detect increased rates of important adverse long-term neurosensory outcomes. Given the evidence of both benefits and harms of treatment, and the limitations of the evidence at present, it appears prudent to reserve the use of late corticosteroids to infants who cannot be weaned from mechanical ventilation and to minimise the dose and duration of any course of treatment.

摘要

背景

產後延緩(>7天)使用皮質類固醇激素治療早產兒慢性肺部疾病

不論是否有過呼吸窘迫症候群(RDS),許多存活的早產兒會繼續發展為慢性肺部疾病(CLD)。這可能是因為肺部持續發炎造成。皮質類固醇激素有著強大的抗炎效果,且已被用於治療確定診斷的CLD。然而還不清楚這些藥物是否利過於弊。

目標

確定與對照(安慰劑或不治療)相比,延遲(> 7天)產後皮質類固醇治療對早產兒CLD的療效。

搜尋策略

檢索Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE(1966年至2002年10月),手工檢索兒科和圍生兒雜誌搜尋產後皮質類固醇治療的隨機對照試驗。檢視以往回顧文章以及從新生兒學臨床專家獲取的訊息。盡可能與所有研究的作者進行聯繫,求證報告的追蹤研究細節,或獲得尚未發表的長期追蹤資料。

選擇標準

本回顧選擇對已造成或將演變成CLD的早產兒在出生後大於7天後才開始使用皮質類固醇治療的隨機對照試驗。

資料收集與分析

提取包括死亡率、CLD(包括需要在家使用氧氣治療,或需用皮質類固醇進行晚期搶救)、死亡或CLD、拔管失敗、初次住院時併發症(包括感染、高血糖症、糖尿、高血壓、腦超音波檢查迴聲強度增加、壞死性小腸結腸炎(NEC)、消化道出血、腸穿孔、腦室出血(IVH)和嚴重早產兒視網膜病變(ROP)),以及長期結果(包括失明、失聰、腦癱和重要感覺神經障礙)在內的相關臨床結果數據,並應用Rev Man 5軟件進行分析。

主要結論

有19項試驗(共收案1345名)符合本回顧納入要求。延緩類固醇治療與新生兒(第28天)死亡率下降有關但與出院時或最晚報告年齡的死亡率沒影響。延緩類固醇治療的益處包括減少3,7,28天及時拔管失敗率、28天及最後月經後36週齡時慢性肺疾率(整體或存活者)、晚期搶救治療需用dexamethasone、出院回家繼續氧氣治療,以及28天及最後月經後36週齡週時死亡或CLD。有增加感染或消化道出血風險的傾向但未增加壞死性小腸結腸炎風險。短期不良反應包括高血糖,糖尿和高血壓。增加嚴重新生兒視網膜病變(整體上,對存活者只有增加傾向),但沒有顯著增加失明。有減少嚴重腦室出血(IVH)傾向但只有5項試驗名247名嬰兒有此項結果報告。有增加腦癱或神經學檢查異常與後期追蹤前死亡的反向傾向相抵消。類固醇組和對照組間在死亡或腦癱的合併發生率上無統計學顯著性差異。類固醇組和對照組間在主要感覺神經障礙,以及死亡或感覺神經障礙合併發生率上無統計學顯著性差異。各組間在孩童晚期其他結果如呼吸功能、血壓或成長沒有差。

作者結論

延緩使用皮質類固醇治療的好處可能未超過其急性或潛在不良反應。儘管對產後類固醇治療(參見“及早開始產後皮質類固醇治療預防早產兒慢性肺病”的回顧)增加嬰兒不良神經學結局發生率的憂慮依然存在,在這針對產後7天後開始使用皮質類固醇治療的回顧顯示晚延遲治療可能減少新生兒死亡率且未增加遠期神經發育不良的風險。然而,評估長期結局的研究在某些方面存在方法學品質問題,某些研究只評估到學齡前兒童,他們某些重要的神經學結果影響不能確定。而且沒有試驗足以偵測重要神經學不良後果增加機率。基於該治療利弊兼有的證據,以及目前證據的限制,較明智的決定是將延遲使用皮質類固醇治療的定位於無法脫離呼吸器的嬰兒,以及減少任何療程的劑量和時間。

翻譯人

本摘要由臺中榮民總醫院葉惠英翻譯。

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

總結

皮質類固醇能降低新生兒慢性肺病(CLD)的肺部發炎但有重大不良反應。CLD是新生兒加護中心新生嬰兒主要問題,而與高死亡率與存活者長期預後惡化相關。持續肺部發炎是CLD最可能的致因。因皮質類固醇抗發炎能力強,所以被用來預防或治療CLD,特別是對無法脫離呼吸器輔助的嬰兒。本回顧發現皮質類固醇對出生大於7天的嬰兒有短期低呼吸器需求與CLD發生率的效果,或許也能減少出生28內的死亡。然而,特別是高劑量時,合併有副作用包括胃腸道出血,高血壓與醣類耐受困難。相對於出生第一週早期使用皮質類固醇,極少證據顯示有長期併發症;但未確定沒有長期的問題。較明智的決定是將延遲使用皮質類固醇治療的定位於無法脫離呼吸器的嬰兒,以及減少任何療程的劑量和時間。

Plain language summary

Late (>7 days) post corticosteroids for chronic lung disease in preterm infants

Corticosteroids can reduce lung inflammation in newborns with chronic lung disease (CLD) but there are major adverse effects of the drugs. CLD is a major problem for newborn babies in neonatal intensive care units, and is associated with both a higher death rate and worse long-term outcomes in survivors. Persistent inflammation of the lungs is the most likely cause of CLD. Because of their strong anti-inflammatory effects corticosteroid drugs have been used to either prevent or treat CLD, particularly in babies who cannot be weaned from assisted ventilation. This review of trials found that giving corticosteroids to infants at least seven days old produces short-term benefits of reducing the need for assisted ventilation and the rate of CLD, perhaps also reducing death in the first 28 days of life. However, high doses in particular are associated with short-term side effects such as bleeding from the stomach or bowel, higher blood pressure and difficulty tolerating glucose. In contrast with early use of corticosteroids in the first week of life, there is little evidence for long-term complications; however, it is not certain that there are no long-term problems. It seems wise to limit the use of late corticosteroids to those babies who cannot be weaned from assisted ventilation and to minimise the dose and duration of any course of treatment.