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.

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.

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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 strategy: 

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.