Intervention Review

Metalloporphyrins for treatment of unconjugated hyperbilirubinemia in neonates

  1. Gautham Suresh1,*,
  2. Christine L Martin2,
  3. Roger Soll3

Editorial Group: Cochrane Neonatal Group

Published Online: 20 JAN 2003

Assessed as up-to-date: 13 NOV 2002

DOI: 10.1002/14651858.CD004207


How to Cite

Suresh G, Martin CL, Soll R. Metalloporphyrins for treatment of unconjugated hyperbilirubinemia in neonates. Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD004207. DOI: 10.1002/14651858.CD004207.

Author Information

  1. 1

    Dartmouth-Hitchcock Medical Center, Department of Pediatrics, Neonatal Division, Lebanon, NH, USA

  2. 2

    University of Vermont College of Medicine, College of Medicine, Burlington, Vermont, USA

  3. 3

    University of Vermont, Division of Neonatal-Perinatal Medicine, Burlington, Vermont, USA

*Gautham Suresh, Department of Pediatrics, Neonatal Division, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, 03576-001, USA. gautham.suresh@hitchcock.org.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 20 JAN 2003

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Metalloporphyrins are heme analogues that inhibit heme oxygenase, the rate-limiting enzyme in the catabolism of heme to bilirubin. By preventing the formation of bilirubin, they have the potential to reduce the level of unconjugated bilirubin in neonates and thereby reduce the risk of neonatal encephalopathy and long term neurodevelopmental impairment from bilirubin toxicity to the nervous system.

Objectives

1. To determine the efficacy of metalloporphyrins in reducing bilirubin levels, reducing the need for phototherapy or exchange transfusion and reducing the incidence of bilirubin encephalopathy in neonates with unconjugated hyperbilirubinemia when compared to placebo, phototherapy or exchange transfusion.

2. To determine the nature and frequency of side effects of metalloporphyrins when used to treat unconjugated hyperbilirubinemia in neonates.

Search methods

We searched Medline (1966 - January 2003) and the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library (2003, issue 1). We hand-searched the articles cited in each publication obtained. We hand searched the abstracts of the Society for Pediatric Research (USA) (published in Pediatric Research) for the years 1985 - 2002.

Selection criteria

We included only randomized controlled studies, in which preterm or term neonates (age 28 days of life or less) with unconjugated hyperbilirubinemia due to any cause were randomly allocated to receive a metalloporphyrin in the treatment arm(s), and to receive a placebo or a conventional treatment (phototherapy or exchange transfusion) or no treatment for hyperbilirubinemia in the comparison arm(s). Any preparation of metalloporphyrin could be used, in any form, by any route, at any dose.

Data collection and analysis

Two authors extracted data independently. Data were entered into Revman by one author and checked by a second author. Prespecified subgroup analyses were planned in term versus preterm infants, hemolytic versus non-hemolytic causes of jaundice and according to the type of metalloporphyrin used.

Main results

Three small studies, enrolling a total of 170 infants, were eligible for inclusion in this review. None blinded intervention or outcome assessment. In all three studies some patients were excluded after randomization. Metalloporphyrin-treated infants appeared to have short-term benefits compared to controls, including a lower maximum plasma bilirubin level in one study, a lower frequency of severe hyperbilirubinemia in one study, a decreased need for phototherapy, fewer plasma bilirubin measurements and a shorter duration of hospitalization. None of the enrolled infants required an exchange transfusion in the two studies that described this outcome. None of the studies reported on neonatal kernicterus, death, long-term neurodevelopmental outcomes or iron deficiency anemia. Though a small number of metalloporphyrin-treated as well as control infants developed a photosensitivity rash, the trials were too small to rule out an increase in the risk of photosensitivity or other adverse effects from metalloporphyrin treatment. No subgroup analyses were possible due to the small number of included trials.

Authors' conclusions

Treatment of neonatal unconjugated hyperbilirubinemia with metalloporphyrins may reduce neonatal bilirubin levels and decrease the need for phototherapy and hospitalization. There is no evidence to support or refute the possibility that treatment with a metalloporphyrin decreases the risk of neonatal kernicterus or of long-term neurodevelopmental impairment due to bilirubin encephalopathy. There is no evidence to support or refute the possibility that cutaneous photosensitivity is increased with metalloporphyrin treatment. Routine treatment of neonatal unconjugated hyperbilirubinemia with a metalloporphyrin cannot be recommended at present.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Metalloporphyrins for treatment of unconjugated hyperbilirubinemia in neonates

Metalloporphyrins may reduce very high levels of jaundice in newborn babies, but more research is required on safety and to compare it with other treatments. Jaundice is very common in newborn babies, and is caused by the liver producing too much bilirubin, a yellow-coloured bile substance. A very high level of bilirubin can damage the developing brain, and is treated with phototherapy (light therapy) or exchange transfusions. Metalloporphyrins are drugs that can prevent the formation of bilirubin, but they might also cause photosensitivity (sensitivity to light) and anaemia (decreased hemoglobin levels in the blood). The review of trials found some evidence that metalloporphyrins might be able to reduce bilirubin, but more research is needed on short and long-term effects and to compare it with other treatments.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

紫質金屬錯合物 (metalloporphyrin) 治療新生兒高間接膽色素血症 (unconjugated hyperbilirubinemia)

紫質金屬錯合物是抑制血基質氧化 (heme oxygenase) 的血基質 (heme) 類似物。血基質氧化是血基質代謝形成膽色素中的速率決定酵素 (ratelimiting enzyme) 。藉由防止膽色素的形成,紫質金屬錯合物有可能降低新生兒間接膽色素的濃度,因而降低新生兒腦病變 (encephalopathy) 及因膽色素對神經系統的毒性造成長期神經發育障礙的風險。

目標

目的在 (1.) 確定紫質金屬錯合物,與安慰劑、照光治療、或換血相較下,在下列各方面的效力:降低膽色素、減少照光治療或換血、以及減少罹患高間接膽色素血症的新生兒的腦病變發生率。 (2.) 確定當紫質金屬錯合物用來治療新生兒高間接膽色素血症時,副作用的性質與發生頻率。

搜尋策略

我們搜尋Medline (1966 到2003一月) 及由Cochrane Library (2003, issue 1) 發佈的Cochrane Controlled Trials Register (CCTR) 。手工查閱已尋得的出版品中引述的文章。手工查閱the Society for Pediatric Research (USA) (於Pediatric Research發行) 從1985年至2002年間的摘要。

選擇標準

我們僅收錄隨機分配對照的研究,其中對象是早產或足月因任何原因罹患高間接型膽色素血症的新生兒 (年齡小於或等於28天大) ,隨機分配在接受紫質金屬錯合物的治療組及接受安慰劑、傳統治療 (照光或換血) 或無治療的對照組。任何紫質金屬錯合物製劑都可經由任意型態、途徑、及劑量使用。

資料收集與分析

2位作者各自不相干涉地取得資料。資料由1位作者鍵入Revman並由第2位作者核對。關於預定子群體的分析,計畫依足月對早產、溶血性對非溶血性黃疸、以及所使用的紫質金屬錯合物的種類來區分。

主要結論

3個小型研究共收集170個嬰兒符合本評論的收錄標準。對使用的治療方式及結果評估醫師及病患家長皆知情。3個研究皆有部分患者在隨機分配後被排除。紫質金屬錯合物治療過的嬰兒與對照組相較下顯示有短期效益,包括:1個研究中有較低的最高血清膽色素、1個研究中有較低的嚴重高膽色素血症發生率、減少照光的需要、較少次血清膽色素測量、以及較短住院日數。2個提到換血研究中所登記的嬰兒都沒有換血的需要。沒有研究提及新生兒核黃疸 (neonatal kernicterus) 、死亡、長期神經發育狀況、或缺鐵性貧血。雖然少數紫質金屬錯合物治療的嬰兒,如同對照組,產生光敏感性紅疹 (photosensitivity rash) ,但試驗的規模太小,不足以排除紫質金屬錯合物治療造成光敏感或其他副作用增加的風險。由於收錄試驗的數量不足,子群體的分析皆無法進行。

作者結論

用紫質金屬錯合物治療新生兒高間接膽色素血症可能會降低新生兒膽色素並減少照光或住院的需要。沒有證據支持或反駁紫質金屬錯合物治療有可能會降低新生兒核黃疸,或因膽色素腦病變造成長期神經發育障礙的風險。沒有證據支持或反駁紫質金屬錯合物治療有增加皮膚光敏感的可能性。目前尚不能推薦使用紫質金屬錯合物來常規治療新生兒高間接膽色素血症。

翻譯人

本摘要由馬偕醫院林佳瑩翻譯。

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

總結

紫質金屬錯合物可能降低新生兒的高度黃疸,但需要進一步的探究其安全性及與其他治療方式的比較。由於肝臟產生太多膽色素 (黃色膽汁樣物質) ,黃疸在新生兒相當常見。很高的膽色素會損害發育中的大腦,並且使用照光 (光療, light therapy) 或換血來治療。紫質金屬錯合物是可以防止膽色素形成的藥物,但也可能造成光敏感 (photosensitivity, sensitivity to light) 及貧血 (降低血中血紅素 (hemoglobin)) 。本評論找到一些證據:紫質金屬錯合物可能可以降低膽色素,但需要進一步探究短期及長期效果,並與其他治療方式相比較。