Intervention Review

Early volume expansion for prevention of morbidity and mortality in very preterm infants

  1. David A Osborn1,*,
  2. Nicholas J Evans2

Editorial Group: Cochrane Neonatal Group

Published Online: 19 APR 2004

Assessed as up-to-date: 30 JUL 2008

DOI: 10.1002/14651858.CD002055.pub2

How to Cite

Osborn DA, Evans NJ. Early volume expansion for prevention of morbidity and mortality in very preterm infants. Cochrane Database of Systematic Reviews 2004, Issue 2. Art. No.: CD002055. DOI: 10.1002/14651858.CD002055.pub2.

Author Information

  1. 1

    Royal Prince Alfred Hospital, RPA Newborn Care, Camperdown, New South Wales, Australia

  2. 2

    Royal Prince Alfred Hospital, Neonatal Medicine, Camperdown, NSW, Australia

*David A Osborn, RPA Newborn Care, Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales, 2050, Australia.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 19 APR 2004




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


Reduced perfusion of organs such as the brain, heart, kidneys and the gastrointestinal tract may lead to acute dysfunction and be associated with permanent injury. Various strategies have been used to provide cardiovascular support to preterm infants including inotropes, corticosteroids and volume expansion.


To determine the effect of early volume expansion on morbidity and mortality in very preterm infants. If volume expansion is effective, to determine the type of volume expansion that is most effective.

Search methods

The standard search strategy of the Neonatal Review Group was used. Updated searches were performed of the Cochrane Central Register of Controlled Trials (Issue 3, 2008), MEDLINE (1996 - July 2008), EMBASE (1980 - July 2008), previous reviews including cross references, abstracts and conferences.

Selection criteria

Randomised trials of early volume expansion with normal saline, fresh frozen plasma, albumin, plasma substitutes or blood compared to no treatment or another form of volume expansion in preterm infants ≦ 32 weeks gestation or ≦ 1500 g were included. Volume expansion was defined as at least 10 ml/kg given in the first 72 hours after birth.

Data collection and analysis

Standard methods of the Neonatal Review Group with use of relative risk (RR), risk difference (RD) and weighted mean difference (WMD). The fixed effects model was used for meta-analysis. Data from individual studies were only eligible for inclusion if a least 80% of infants were reported for that outcome.

Main results

Eight studies were included. Five studies compared volume to no treatment. Most studies enrolled very preterm infants on the basis of gestation or birthweight. Two studies comparing different types of volume expansion enrolled very preterm infants with hypotension. No study enrolled infants on the basis of low blood flow. One study examined the effect of volume expansion on blood flow, but evaluated normotensive very preterm infants.

Four studies comparing volume expansion and no treatment with a total of 940 very preterm infants reported no significant difference in mortality (typical RR 1.11, 95% CI 0.88, 1.40). The large NNNI 1996 study reported no significant difference in severe disability (RR 0.80, 95% CI 0.52, 1.23), cerebral palsy (RR 0.76, 95% CI 0.48, 1.20) and combined death or severe disability (RR 1.00, 95% CI 0.80, 1.24). Although one small study (Beverley 1985) reported reduced P/IVH with volume expansion, this was not supported by any other study. No significant difference was reported in grade 3-4 P/IVH and combined death or grade 3-4 P/IVH. One study (NNNI 1996) reported no significant difference in the incidence of hypotension. The finding of decreased necrotising enterocolitis and increased sepsis in infants who received fresh frozen plasma compared to no treatment in one study should be treated with caution. No significant differences in mortality or disability were found in this study. Comparing albumin and saline in hypotensive infants, one study (Lynch 2008) reported a significant increase in mean BP and reduced incidence of treatment failure (persistent hypotension treated with dopamine). The other study (So 1997) and the meta-analysis of the two studies found no significant difference in treatment failure (typical RR 0.76, 95% CI 0.54, 1.07) or in any other clinical outcome.

Authors' conclusions

There is no evidence from randomised trials to support the routine use of early volume expansion in very preterm infants without cardiovascular compromise. There is insufficient evidence to determine whether infants with cardiovascular compromise benefit from volume expansion. There is insufficient evidence to determine what type of volume expansion should be used in preterm infants (if at all) or to determine the benefit of using early red cell transfusions. The significance of the finding of a significant increase in blood pressure in hypotensive preterm infants in one trial comparing albumin and saline is unclear, but the overall meta-analyses found no other significant clinical benefit in using albumin compared to saline.


Plain language summary

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

Early volume expansion for prevention of morbidity and mortality in very preterm infants

Early volume expansion for very preterm babies has not been shown to improve their outcomes but more research is needed. Low blood pressure and blood flow have been linked to brain injury in preterm babies. They can also cause permanent injury to other organs and developmental problems. One way of trying to increase the blood pressure and flow of blood is to increase the amount of fluid in the blood stream (volume expansion). This can be done with products such as albumin (a protein) and salt solutions. The review of evidence from trials found that volume expansion has not been shown to improve outcomes for preterm babies. More research is needed.



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





早期容積擴張降低極早早產兒的發病率和死亡率嗎? 如果容積擴張有效,哪類容積擴張法最有效?


使用新生兒評價組的標準檢索策略進行檢索, 更多的情況見評價組詳情。以上檢索中補充增加了對牛津圍生兒試驗數據庫、Cochrane對照試驗中心註冊資料庫(CENTRAL,Cochrane圖書館,2004年第1期)、MEDLINE (1996年 2004年1月)、EMBASE (1980年 2004年1月)、含參考文獻的以往評價/綜述(參考了全部文章)、摘要和會議(澳大利亞和新西蘭圍生兒學會,以及兒科學術學會和美國兒科學術學會1998年-2003年的會議)的檢索。


納入以生理鹽水、新鮮冷凍血漿、白蛋白、血漿替代品或血液對小於32孕週或小於1500克的新生兒進行早期容積擴張,與不治療或另一種容積擴張法進行比較的隨機試驗。容積擴張的定義為出生後頭72小時至少補充10 毫升/公斤。


新生兒評價組的標準方法,使用相對危險度(RR),風險差(RD)和加權均數差(WMD)。使用RevMan 4.1軟件,以固定效應模型進行Meta分析。只有報告了該結局的嬰兒至少佔80%,單項研究的數據才符合納入要求。


納入七項研究。五項研究(其中四項有死亡率數據)對容積擴張與不治療進行比較。大多數研究根據孕齡或出生體重徵集極早出生早產兒。兩項比較不同類型容積擴張的研究,徵集低血壓的極早出生早產兒。沒有研究根據低血流 量徵集嬰兒。有一項研究評估容積擴張對血流的影響,但這是正常血壓的極早出生早產兒。





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