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Vitamin E supplementation for prevention of morbidity and mortality in preterm infants

  1. Luc P Brion1,*,
  2. Edward F Bell2,
  3. Talkad S Raghuveer3

Editorial Group: Cochrane Neonatal Group

Published Online: 20 OCT 2003

Assessed as up-to-date: 30 MAR 2007

DOI: 10.1002/14651858.CD003665


How to Cite

Brion LP, Bell EF, Raghuveer TS. Vitamin E supplementation for prevention of morbidity and mortality in preterm infants. Cochrane Database of Systematic Reviews 2003, Issue 4. Art. No.: CD003665. DOI: 10.1002/14651858.CD003665.

Author Information

  1. 1

    University of Texas Southwestern at Dallas, Division of Neonatal-Perinatal Medicine, Dallas, Texas, USA

  2. 2

    University of Iowa, Department of Pediatrics, Iowa City, Iowa, USA

  3. 3

    University of Kansas Medical Center, Pediatrics, Kansas City, USA

*Luc P Brion, Division of Neonatal-Perinatal Medicine, University of Texas Southwestern at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas, 75390-9063, USA. Luc.Brion@UTSouthwestern.edu.

Publication History

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

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Abstract

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

Background

Treating very low birth weight (VLBW) infants with pharmacologic doses of vitamin E as an antioxidant agent has been proposed for preventing or limiting retinopathy of prematurity, intracranial hemorrhage, hemolytic anemia, and chronic lung disease. However, excessive doses of vitamin E may result in concerning side effects.

Objectives

To assess the effects of vitamin E supplementation on morbidity and mortality in preterm infants.

Search methods

MEDLINE (October 2002), EMBASE (March 2002), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2003), and personal files for clinical trials assessing vitamin E in preterm infants were searched. The MEDLINE and CCTR searches were updated in March 2007.

Selection criteria

Trials analyzing primary outcomes (mortality or combined long-term morbidity) or secondary outcomes (other morbidity) in infants with gestational age less than 37 weeks or birth weight less than 2500 grams were selected. The intervention was allocation to routine supplementation with vitamin E in the treatment group versus placebo, no treatment or another type, dose or route of administration of vitamin E.

Data collection and analysis

The standard methods of the Cochrane Collaboration and of the Cochrane Neonatal Review Group were used.

Main results

Twenty-six randomized clinical trials fulfilled entry criteria. No study assessed combined long-term morbidity. Routine vitamin E supplementation significantly increased hemoglobin concentration by a small amount. Vitamin E significantly reduced the risk of germinal matrix/intraventricular hemorrhage and increased the risk of sepsis; however, heterogeneity limits the strength of these latter two inferences. Vitamin E did not significantly affect other morbidity or mortality. In VLBW infants, vitamin E supplementation significantly increased the risk of sepsis, and reduced the risk of severe retinopathy and blindness among those examined.
Subgroup analyses demonstrated (1) an association between intravenous, high-dose vitamin E supplementation and increased risk of sepsis and of parenchymal cerebral hemorrhage; (2) an association between vitamin E supplementation by other than the intravenous route and reduced risk of germinal matrix-intraventricular hemorrhage and of severe intraventricular hemorrhage; and (3) an association between serum tocopherol levels greater than 3.5 mg/dl and increased risk of sepsis and reduced risk for severe retinopathy among those examined.

Authors' conclusions

Vitamin E supplementation in preterm infants reduced the risk of intracranial hemorrhage but increased the risk of sepsis. In very low birth weight infants, vitamin E increased the risk of sepsis, and reduced the risk of severe retinopathy and blindness among those examined. Evidence does not support the routine use of vitamin E supplementation by intravenous route at high doses or aiming at serum tocopherol levels greater than 3.5 mg/dl.

 

Plain language summary

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

Vitamin E supplementation for prevention of morbidity and mortality in preterm infants

Giving extra vitamin E to preterm babies can provide some benefits, but it increases the risk of life-threatening infections. Preterm babies (born before 37 weeks) can develop a range of problems because their organs are not mature. Vitamin E may be able to help prevent or limit some of these problems, but it can potentially also have harmful effects. Breast milk of a woman who has given birth prematurely has higher than usual levels of vitamin E. Preterm babies can be given extra vitamin E as vitamin drops, in vitamin E-enriched formula, in intravenous fluids, or by injection into their muscles. This review of studies of vitamin E supplements found that while extra vitamin E reduces the chances of some complications (including disease of the retina), the risk of life-threatening infection is increased. The risk of bleeding in the brain is increased when extra vitamin E is given by vein but decreased when the extra vitamin E is given by other routes.

 

摘要

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

背景

對於補充維他命E來預防早產兒罹病與死亡的情況

以維它命E達到藥理性質之劑量來當作1種抗氧化劑,用來治療非常低出生體重(VLBW)的嬰兒,這方法已經被假設為可以預防或抑制早產兒的視網膜病變、顱內出血、溶血性貧血,以及慢性肺部疾病。然而,維它命E的劑量過高時,可能會產生各種相關的副作用。

目標

對於早產兒們而言,要評估補充維他命E對於罹病與死亡的情況方面所產生的影響。

搜尋策略

搜尋MEDLINE (2002年10月) 、EMBASE (2002年3月) 、Cochrane Central Register of Controlled Trials (CENTRAL, Cochrane Library, Issue 1, 2003) ,以及個人資料以找出以vitamin E用於早產嬰兒的臨床試驗。並於2007年3月更新MEDLINE及CCTR所搜尋的資料。

選擇標準

以妊娠年齡低於37週或是出生時體重低於2500克的嬰兒們為對象,曾經針對他們的主要結果(死亡或是合併後的長期罹病情況)或是次要結果(其他的罹病情況)來進行分析的試驗,就會被挑選進來。其中的介入行為是將嬰兒們分配到固定給予維他命E的治療組當中,而比較的對象則包括了 (1) 安慰劑、 (2) 不採取治療,或是 (3) 其他類型、劑量或是給藥路徑之維它命E的使用。

資料收集與分析

當中使用的是the Cochrane Collaboration以及 the Cochrane Neonatal Review Group的標準方法。

主要結論

共有26份隨機化的臨床試驗完全符合了挑選的標準。沒有任何試驗曾經評估過合併後的長期致病情況。固定補充維他命E之後,可以有意義地讓血紅素的濃度達到某種小幅度的增加。維他命E有意義地讓生長胚質/腦室內出血的風險降低了,而且也提高了產生敗血症的風險;然而,質異性卻侷限了後面這2項推論的力度。維它命E並不能夠對其他的致病情況或是死亡率帶來有意義的影響。有經過眼睛檢查非常低出生體重的嬰兒們,補充維他命E會有意義地讓得到敗血症的風險提高,而且也讓得到嚴重視網膜病變與眼盲的風險降低。次群組方面的分析顯示了(1)以靜脈注射來給予高劑量的維他命E,與敗血症及腦實質出血之風險上升之間,存在著某種關聯;(2)經由靜脈注射以外的路徑來補充維他命E,與生長胚質之腦室內出血及嚴重的腦室內出血之風險下降之間,存在著某種關聯;以及(3)在那些有經過眼睛檢查的對象之中,血清中的維他命E濃度大於3.5 mg/dl,與得到敗血症的風險上升,及得到嚴重之視網膜病變的風險下降,存在著某種關聯。

作者結論

對於早產兒們補充維他命E,可以降低顱內出血的風險,但是卻會提高得到敗血症的風險。對於非常低出生體重的嬰兒們來說,維它命E會讓得到敗血症的風險提高,並且在那些經過眼睛檢查的對象之中,可以讓得到嚴重之視網膜病變與眼盲的風險降低。針對以靜脈注射的方法來固定地給予高劑量之維他命E,或是要維持血清中的維他命E濃度達到大於3.5 mg/dl,目前之證據都不能夠支持這樣的做法。

翻譯人

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

總結

對於早產兒們提供額外的維他命E,可以帶來某些好處,但是這樣的做法也會提高對生命構成威脅之感染的風險。對於早產兒們(在37週之前出生)來說,因為他們的器官都還沒有成熟,所以可能會發展出很多的問題。維它命E或許能夠幫助預防或是抑制某些問題的發生,但是它也可能會帶來潛在的有害影響。對於提早產下嬰兒的婦女來說,她的母乳中會含有比ㄧ般值還要高的維他命E。對於早產的嬰兒們,所提供額外的維他命E,可以選擇不同的型式,包括了維他命的口服滴液、富含維他命E的配方奶、靜脈注射的點滴,或是肌肉注射等方式。本篇關於維他命E的研究回顧發現,額外添加維他命E之後,當它在減少了某些併發症風險(包括了視網膜的疾病)的同時,對生命構成威脅之感染的風險卻提高了。當我們透過靜脈來給予額外的維他命E時,在腦內發生出血的風險會增加,但是如果是透過其他的路徑來給予額外的維他命E時,這種風險就會降低了。