Interventions for growth failure in childhood Crohn's disease
Published Online: 20 JUL 2005
Assessed as up-to-date: 15 MAY 2005
Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
How to Cite
Newby EA, Sawczenko A, Thomas AG, Wilson D. Interventions for growth failure in childhood Crohn's disease. Cochrane Database of Systematic Reviews 2005, Issue 3. Art. No.: CD003873. DOI: 10.1002/14651858.CD003873.pub2.
- Publication Status: Edited (no change to conclusions)
- Published Online: 20 JUL 2005
Crohn's disease in childhood is a chronic relapsing condition. Fifteen to forty per cent of children with Crohn's disease have growth retardation (Griffiths 1993a). Some treatment modalities including corticosteroids have been implicated in growth failure but it is thought mainly to be secondary to uncontrolled disease activity (Motil 1993; Markowitz 1993). Growth is fundamental to the practice of pediatrics, so by taking growth as the primary outcome measure we address issues important to both patients, their families and pediatricians.
To evaluate the effectiveness of the different modalities available for the treatment of childhood Crohn's disease with regard to the reversal of growth failure and the promotion of normal growth.
Searches were made of the following databases using the Collaborative Review Group Search Strategy: EMBASE (1984-2004), MEDLINE (1966-2004), The Cochrane Central Register of Controlled Trials, The Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register and the Science Citation Index. Abstracts from the major gastrointestinal research meetings and references from published articles were also reviewed.
Randomized controlled trials pertaining to children less than 18 years of age with Crohn's disease were selected. Those with growth as an outcome measure were included in the review.
Data collection and analysis
Data extraction and assessment of the methodological quality of each trial was independently reviewed by two reviewers. Only one good quality randomized controlled trial was included in the review and therefore no statistical analysis was possible.
Three randomized controlled trials were identified. One was of good methodological quality (Markowitz 2000). This study looked at the use of 6-mercaptopurine (6-MP) as a steroid sparing agent. No difference in linear growth was observed between the intervention and placebo groups, although the total steroid dose received over the 18 month follow up period was reduced in the group receiving 6-MP. The two remaining randomized controlled trials (Sanderson 1987; Thomas 1993a) consider the use of enteral feeding versus corticosteroids for induction of remission, with height velocity standard deviation score at 6 months as an outcome measure. Although of less rigorous methodological quality, the results of these studies are discussed in detail in the review. In both studies height velocity standard deviation scores were significantly increased in the enteral feeding group compared with the corticosteroid group.
In addition to these randomized controlled trials, a body of lower quality evidence does exist relevant to two other important interventions; the use of supplemental enteral nutrition (Morin 1980; Belli 1988; Israel 1995) and the judicious use of surgical interventions in pre-pubertal children with refractory disease (Alperstein 1985; Lipson 1990; McLain 1990). Newer treatments, such as infliximab, are now becoming more widely used and may offer advantages in promoting growth. These effects are as yet unstudied. This review highlights the need for large, multi centre studies of the different treatment options in paediatric Crohn's disease and the importance of standardised measurements of growth, such as height velocity standard deviation scores and height standard deviation scores as outcome measures.
Plain language summary
Interventions for growth failure in childhood Crohn's disease
Growth failure occurs in 15-40% of children with Crohn's disease. Growth in affected children is influenced by the disease process itself and by some treatments. Management in children differs from that in adults because of the required emphasis on achieving optimum growth and pubertal development. The aim of this review was to evaluate the effectiveness of various treatments for growth failure in childhood Crohn's disease. Three randomized controlled trials were identified. One trial did not show any benefit for linear growth with 6-mercaptopurine treatment compared to placebo among children being treated with steroids. The other two trials looked at nutritional treatment (elemental feedings) versus steroids (prednisolone). Both trials showed a statistically significant benefit for height velocity standard deviation scores with nutritional treatment. However, these results need to be confirmed by large, multi-centre, randomized controlled trials of therapeutic interventions in pre-pubertal children with Crohn's disease. These trials should use growth as an outcome measure. In conclusion, more research is needed to identify effective treatments for growth failure in childhood Crohn's disease.
孩童期克隆氏症是一種慢性復發的疾病，有15至40% 的患有克隆氏症的兒童會出現生長遲緩的情形 (Griffiths 1993a) ，有些治療方式像是皮質類固醇已經被用來治療生長障礙，但是相對於無法控制疾病活性來說，這都是次要的 (Motil 1993; Markowitz 1993) 。以兒科來說，生長是最根本的基礎，因此我們以生長為主要的量測結果，處理這個對於病患、病患家屬和兒科醫師來說都相當重要的議題。
搜尋以下資料庫，並使用 Collaborative Review Group 搜尋策略: EMBASE (1984 – 2004) 、MEDLINE (1966 – 2004) 、Cochrane Central Register of Controlled Trials、Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register and the Science Citation Index。並且還回顧了以腸胃道研究為主的研討會論文摘要，以及已發表研究論文的參考文獻。
一共找出三篇隨機對照試驗。其中一篇試驗具有良好的方法學品質 (Markowitz 2000) ，這個研究探討以6mercaptopurine作為類固醇激發劑(steroidsparing agent)的效果，發現儘管6mercaptopurine組在後續18個月的追蹤期間接受的類固醇總量減少了，但6mercaptopurine組和安慰劑組在線性生長上並沒有觀察到差異。其他兩個隨機對照試驗 (Sanderson 1987; Thomas 1993a) 則比較腸道餵食和類固醇引發的緩解效果，並以六個月的身高速度標準差評分 (height velocity standard deviation score) 為主要評估成果，雖然研究方法較不嚴謹，但其研究結果仍會在本文獻回顧中進行詳細的討論。在這兩個試驗中，身高速度標準差異評分結果顯示，腸道餵食組相較於類固醇組，其身高生長速度明顯的增加。
除了這些隨機對照試驗以外，還有一些品質較低的證據支持其他重要介入措施，包括使用腸道營養補給品 (Morin 1980; Belli 1988; Israel 1995) ，以及對患有難治疾病的前青春期兒童審慎地以手術介入治療 (Alperstein 1985; Lipson 1990; McLain 1990) 。新式治療法，如infliximab，現在已經被廣泛地使用且可能有助於促進生長，但是這些影響尚未被研究。本回顧凸顯出對小兒克隆氏症的各種治療方式，還需要更多大型、多中心的研究來了解，以及兒童生長標準化測量工具的重要性，例如以身高速度標準差評分和身高標準差評分為主要的評估項目。
此翻譯計畫由臺灣國家衛生研究院 (National Health Research Institutes, Taiwan) 統籌。
需要進行更多研究來確認，對於患有克隆氏症的兒童，如何治療生長遲緩才是有效的。患有克隆氏症的兒童有15% 至40% 會出現生長遲緩的現象，其生長會受疾病本身的進展以及治療方式所影響。兒童的疾病處理和成人不同，因為對兒童來說，要特別注意能夠達到適當促進其身高生長和青春期的發展。本文獻回顧的目的在於評估治療生長遲緩的不同方式，對於患有克隆氏症兒童的成效。我們共找到三個隨機對照試驗，其中一個試驗顯示，對正在接受類固醇治療的兒童而言，6mercaptopurine相較於安慰劑並未在線性成長上帶來助益。另外兩個試驗則是著重在營養治療 (元素餵食) 和類固醇 (prednisolone) 的比較上，兩個試驗都顯示營養治療能顯著提升身高速度標準差評分。這些結果還需要更多大型、多中心的隨機對照試驗來確認，以了解克隆氏症青春期兒童的治療介入，且這些試驗應該以生長狀況為主要評估項目。