New information added includes identification of one new eligible study (Lynch 2002) comparing albumin and saline. Updated searches identified several studies that did not meet inclusion criteria. Data from one unpublished study (Wright 1995) have still not been obtainable from author.
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 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.
The standard search strategy of the Neonatal Review Group was used. See Review Group details for more information. This was supplemented by additional searches of the Oxford Database of Perinatal Trials, and updated search performed of the Cochrane Central Register of Controlled Trials (CENTRAL, Cochrane Library Issue 1, 2004), MEDLINE (1996-January 2004), EMBASE (1980-January 2004), previous reviews including cross references (all articles referenced), abstracts and conferences (Perinatal Society of Australia and New Zealand, and Pediatric Academic Societies and American Academy of Pediatrics meetings 1998-2003).
Comparing volume and no treatment, 4 studies with a total of 940 very preterm infants reported no significant difference in mortality (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 a gelatin-based plasma substitute or 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 2002) reported a significant increase in mean BP and reduced incidence of treatment failure (persistent hypotension). The other study (So 1997) and the meta-analysis of the two studies found no significant difference in treatment failure (RR 0.75, 95% CI 0.53, 1.06) or in any other clinical outcome.
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. Twenty percent of surviving babies born very premature do so with some degree of neurodevelopmental disability (Lorenz 1998). Low systemic blood pressure and blood flow have both been linked to cerebral injury in preterm infants. Systemic arterial hypotension is associated with peri/intraventricular haemorrhage (P/IVH), ischaemic cerebral lesions and poor long term neurodevelopmental outcome (Miall-Allen 1987; Goldstein 1995; Low 1993). Low upper body blood flow (Kluckow 2000; Osborn 2003) and low cerebral blood flow (Meek 1999) on the first day of life are associated with late P/IVH (Kluckow 2000; Osborn 2003). In addition, in the studies by Kluckow 2000 and Osborn 2003, low upper body blood flow on the first day of life (as measured by flow in the superior vena cava) was associated with a significant increase in mortality in infants born < 30 weeks' gestation.
Clinical features suggesting reduced perfusion include low blood pressure, reduced cutaneous perfusion and metabolic acidosis. However, systemic arterial pressure has been shown to be poorly correlated with systemic blood flow as measured by Doppler ultrasound in preterm infants (Kluckow 1996; Kluckow 2000; Osborn 2001b). In addition, clinical measures of hypovolaemia including systemic hypotension have been found to be poorly correlated to blood volume in premature infants (Barr 1977; Bauer 1993).
Various therapeutic strategies have been used to provide cardiovascular support to preterm infants including inotropes, corticosteroids and volume expansion. Most strategies have targeted low blood pressure using inotropes such as dopamine and dobutamine (Greenough 1993; Hentschel 1995; Klarr 1994; Roze 1993) and corticosteroids (Bourchier 1997). Despite an increase in systemic blood pressure, dopamine was shown to reduce aortic blood flow in one study (Roze 1993). In another study in very preterm infants with low systemic blood flow (SBF), dobutamine which produced little change in blood pressure resulted in a significantly greater increase in SBF than dopamine, which produced a significantly greater increase in blood pressure (Osborn 2002). Strategies to correct systemic hypotension and hypovolaemia have also included volume expansion. Observational studies have found increases in cardiac output after albumin infusion in sick preterm infants (Pladys 1997) and a small increase in systemic blood pressure (Barr 1977; Bignall 1989). Observational studies have also found an increased incidence of P/IVH (Goldberg 1980) and chronic lung disease (Van Marter 1990) in preterm infants receiving volume expansion. A systematic review of albumin infusions in critically ill patients including those with hypovolaemia, burns and hypoalbuminaemia found a significantly increased mortality for those patients receiving albumin compared to control (Alderson 2004).
The question addressed by this review is what is the evidence from randomised controlled trials for the use of early volume expansion to prevent mortality and morbidity in very preterm infants. In view of the difficulties of identifying infants with poor perfusion and hypovolaemia, subgroup analysis was planned according to method of diagnosis of poor perfusion (unselected preterm infants, preterm infants with clinical indicators of poor perfusion [low blood pressure, reduced cutaneous perfusion and metabolic acidosis] and infants with ultrasound Doppler detected low blood flow). As there is evidence to suggest that late intraventricular haemorrhage is associated with systemic hypotension and low systemic blood flow in the first day of life (Miall-Allen 1987; Goldstein 1995; Kluckow 2000; Osborn 2003), subgroup analysis was performed with the hypothesis that trials that used early volume expansion were more likely to prevent intraventricular haemorrhage. As different volume expanders have different effects, subgroup analysis was performed according to type of volume expansion used. This is an update of a previous Cochrane Review (Osborn 2001).
In very preterm infants, to determine if early volume expansion reduces morbidity and mortality. Subgroup analysis was planned according to method of diagnosis of poor perfusion (unselected preterm infants, preterm infants with clinical indicators of poor perfusion and infants with ultrasound Doppler detected low blood flow), postnatal age of treatment and type of volume expansion used. In trials among such infants which compare two or more different types of infusate for volume expansion, to determine which type is more effective.
Secondary outcome measures included any of the following;
1. Use of inotropes (in first 72 hours)
2. Failure to correct low systemic blood flow (eg Doppler ultrasound after volume expansion)
3. Failure to correct systemic hypotension (enrolment criteria used in trial)
4. Patent ductus arteriosus (PDA)
5. Renal impairment (creatinine >= 120 micromol/l, oliguria <= 0.5mls/kg/hour)
6. Airleak
7. Chronic lung disease (CLD) (at 28 postnatal days or near term postmenstrual age)
8. Proven necrotising enterocolitis
9. Retinopathy of prematurity (any grade and severe)
Planned subgroup analyses included the following identified subcategories:
1. Including only trials where volume expansion was given a) in the first day of life, and b) in the first 12 hours of life
2. According to type of volume expansion used (normal saline, fresh frozen plasma, albumin, plasma substitute or blood)
3. According to whether trials enrolled:
The standard search strategy of the Neonatal Review Group was used. See Review Group details for more information. This was supplemented by additional searches of the Oxford Database of Perinatal Trials, and updated search performed of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 1, 2004), MEDLINE (1996-January 2004), EMBASE (1980-January 2004), previous reviews including cross references (all articles referenced), abstracts and conferences (Perinatal Society of Australia and New Zealand, and Pediatric Academic Societies and American Academy of Pediatrics meetings 1998-2003).
The search of MEDLINE included both MeSH searches using the following terms ("[colloids or plasma substitutes or sodium chloride or serum albumin or hypotension] and infant-premature") and text searches using the following terms ("[colloid or crystalloid or saline or volume or hypotension] and infant-premature"). No language restriction was used.
Criteria and methods used to assess the methodological quality of the included trials: Standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. The methodological quality of each trial was reviewed independently by the second author. Particular emphasis was placed on allocation concealment, blinding, completeness of follow up and blinding of outcome assessment. Allocation concealment was ranked: Grade A: adequate; Grade B: uncertain; Grade C: clearly inadequate. Additional information was requested from authors of each trial to clarify methodology (see 'table of included studies' - 'notes').
Methods used to collect data from the included trials: Each author extracted data separately then compared and resolved differences. Additional data where required was requested from authors of trials (see 'table of included studies' - 'notes').
Methods used to synthesise the data: Standard methods of Neonatal Review Group with use of relative risk and weighted mean difference where appropriate. The fixed effects model using RevMan 4.2 was used for meta-analysis. Sensitivity analysis was performed on the basis of methodological quality.
Seven studies were eligible for inclusion (see 'table of included studies'). The author of one potentially eligible but unpublished study has been contacted to obtain details of the study (Wright 1995).
Infants: The largest study was the NNNI 1996 study with 776 enrolled. The other studies were all small with between 25 and 102 infants randomised. Infant numbers, weights and gestations are documented in the 'table of included studies'. Four studies enrolled very preterm infants on the basis of prematurity or low birth weight, not on the basis of haemodynamic compromise (Beverley 1985; Ekblad 1991; Gottuso 1976; NNNI 1996). Emery 1992 enrolled infants with a systolic BP < 40 mmHg. Infants with clinical volume overload were excluded. Infants in the study by Lundstrom 2000 were enrolled if the mean blood pressure was in the normal range (29-40 mmHg) and they had not received volume or inotrope in the preceding 3 hours. The authors state that this group were considered to be above the presumed normal upper limit for hypotension but from previous work may still be at risk of low left ventricular output and cerebral blood flow. Lynch 2002 enrolled hypotensive infants before 3 days of age and with mean BP <5th percentile. So 1997 enrolled mechanically ventilated preterm infants with hypotension (low mean BP according to birthweight strata).
Interventions: Beverley 1985 compared fresh frozen plasma 10 mls/kg on admission and repeated at 24 hours of age to no treatment. Ekblad 1991 compared fresh frozen plasma 10 mls/kg (given over 3 hours at < 5 hours of age, then daily for 3 days) to no treatment. Emery 1992 compared fresh frozen plasma to albumin 4.5% (15 mls/kg over 3 hours) given to infants on day 1 to 4 of life. A control group given albumin 20% 5 mls/kg is not included in this review. Gottuso 1976 compared fresh frozen plasma 15 mls/kg to no treatment (supportive care only) in infants < 24 hours of age. Lundstrom 2000 compared albumin 20% 15 mls/kg to no treatment in infants with a mean postnatal age of 32 hours (range 5-224). Lynch 2002 compared albumin 10mls/kg with normal saline 10mls/kg infused over 20 minutes in infants <3 days of age. Volume was repeated if hypotension persisted. The NNNI 1996 study compared infants < 2 hours of age randomised to either fresh frozen plasma 15 mls/kg, a gelatin-based plasma substitute (Gelofusine) 20 mls/kg (given over 15 minutes and repeated after 24 hours) or to no treatment. So 1997 compared infants randomised to albumin 5% or normal saline 10 mls/kg over 30 minutes, with a maximum of 3 doses given if hypotension persisted.
Outcomes: the stated primary outcomes for the studies included P/IVH (Beverley 1985), water balance and renal function (Ekblad 1991), systolic blood pressure 1 and 4 hours after infusion (Emery 1992), haemodynamic change (mean BP, left ventricular output and cerebral blood flow) (Lundstrom 2000), change in mean BP (%) (Lynch 2002), death before discharge or severe disability at 2 years (NNNI 1996) and successful treatment of hypotension (So 1997). The data for treatment failure in the studies by Lynch 2002 and So 1997 are the number of infants with persistent hypotension after volume therapy requiring inotropes. Gottuso 1976 did not state a primary outcome but measured mortality and blood gas data. Data from the NNNI 1996 study for grade 1 P/IVH, grade 2-4 P/IVH and periventricular leucomalacia were available from a subgroup of units with routine scan facilities. Data from this study for grade 3-4 P/IVH included late cystic parenchymal lesions. The data for severe neurodevelopmental disability included children who were blind, deaf, unable to walk, had a developmental quotient > 3 SD below mean or another severe disability. Hypotension in the NNNI 1996 study was defined as systolic blood pressure < 35 mmHg. Treatment failure in this study was defined as the occurrence of hypotension on the first day of life and was only available for a subgroup of infants born in 1990 and 1991.
Thirty seven reports did not meet inclusion criteria (see 'characteristics of excluded studies'). These included 11 studies which had no control group (Alkalay 1999; Barr 1977; Bauer 1993; Bignall 1989; Dimitriou 2001; Lambert 1998; Lay 1980; Nelle 1997; Pladys 1994; Pladys 1997; Sriram 1997). Two studies used insufficient volume to be eligible for inclusion, with less than 10 mls/kg volume given (Bland 1976; Greenough 1993). One of these also enrolled infants with a mean gestational age >32 weeks (Bland 1976). Four studies of red cell transfusion were in infants >3 days old (Beeram 2003; Blank 1984; Meyer 1993; Nose 1996). One study printed in abstract form only did not state volume of fresh frozen plasma given and data for analysis could not be extracted (Alexander 1976). Oca 2003 comparing volume expansion with albumin to normal saline enrolled hypotensive infants stratified by birth weight <2500g or >=2500g. There were excess losses (23%) in the <2500g strata to meet eligibility for inclusion in the review.
See the 'Table of included studies'.
One included study is only reported in abstract form to date (Lynch 2002). Six studies reported adequate randomisation procedures and had adequate allocation concealment (Beverley 1985; Emery 1992; Gottuso 1976; Lundstrom 2000; NNNI 1996; So 1997). Two studies did not report the method of randomisation (Ekblad 1991; Lynch 2002). Lynch 2002 reported 'blinding' but did not report method or what components of the study were blinded. No other study stated that the interventions were blinded in any way. Given the nature of the interventions it is unlikely that it was possible to blind caregivers in any of the studies. Blinding measurement of outcomes was reported by Beverley 1985 (P/IVH) and the NNNI 1996 study (neurodevelopmental assessment). Studies reporting no losses to follow up included Emery 1992; Gottuso 1976; Lundstrom 2000; NNNI 1996 study (neurodevelopmental assessment) and So 1997. Beverley 1985 reported 7 (12.5%) losses. Data for P/IVH for the excluded infants is available and used in the analysis of mortality and P/IVH in this review. Ekblad 1991 reported outcomes for the same cohort of infants in 2 papers, with data reported on 38 of 40 infants in one paper (PDA) and 35 of 40 (renal function) in the other. Data for P/IVH and mortality for the excluded infants is available and used in the analysis of these outcomes in this review. The grade of P/IVH was not available for the excluded infants. The authors have been contacted to obtain this information. Data for PDA were not available for 2 infants. Lynch 2002 did not report post randomisation losses so losses are unclear. Not all units in the NNNI 1996 study performed routine head ultrasound scans. Data for P/IVH were available for approximately 84% of 611 infants from centres with routine scan facilities. The NNNI 1996 study reported head ultrasound abnormalities in units with routine scanning facilities as intraventricular haemorrhage and periventricular abnormality in babies surviving at 6 weeks. This was then reclassified into subependymal haemorrhage, more severe haemorrhage, any cerebral abnormality, severe cerebral abnormality, and death or severe cerebral abnormality. Approximately 84% of surviving infants had data from both 1 and 6 weeks' ultrasounds. Only data from this subgroup of units with > 80% follow up and from surviving infants with both 1 and 6 weeks scans have been used in this review.
As the ascertainment of head ultrasound abnormality was different between the studies, data for P/IVH, grade 2-4 P/IVH, grade 3-4 P/IVH and periventricular leucomalacia are only combined in meta-analysis in studies that report similar methods of ascertainment. Data are included where there is > 80% ascertainment of infants for the outcome.
See 'MetaView tables'.
VOLUME VERSUS NO TREATMENT
Primary outcomes: Five studies randomised infants to volume versus no treatment (Beverley 1985; Ekblad 1991; Gottuso 1976; Lundstrom 2000; NNNI 1996). Four studies with a total of 940 infants reported mortality (Beverley 1985; Gottuso 1976; Lundstrom 2000; NNNI 1996).
None found a significant effect. Meta-analysis showed the mortality was similar
for infants who received volume compared to no treatment (pooled relative
risk 1.11, 95% confidence intervals 0.88, 1.40; risk difference 0.02, 95%
CI -0.03, 0.08). Two of these studies (Beverley 1985; Ekblad 1991) reported P/IVH data on all infants randomised. Beverley 1985 found a significant reduction in P/IVH (RR 0.46, 95% CI 0.21, 0.98) whereas Ekblad 1991
found no significant difference (RR 1.21, 95% CI 0.31, 4.71). Meta-analysis
of these 2 studies showed no significant difference in P/IVH (RR 0.58, 95%
CI 0.30, 1.11; RD -0.14, 95% CI -0.29, 0.01). Beverley 1985
found no significant difference in grade 2-4 P/IVH (RR 0.43, 95% CI 0.17,
1.08) or grade 3-4 P/IVH (RR 0.55, 95% CI 0.21, 1.47); the difference in
rate of death or P/IVH was of borderline significance (RR 0.55, 95% CI 0.30,
1.03; RD -0.21, 95% CI -0.42, -0.01). There was no significant difference
in death or grade 3-4 P/IVH (RR 0.68, 95% 0.32, 1.46). For the 413 survivors
who were examined at 6 weeks in centres with routine scan facilities in the
NNNI 1996 study, no significant difference was
found in P/IVH in survivors (RR 1.05, 95% CI 0.75, 1.47) or grade 2-4 P/IVH
in survivors (RR 1.03, 95% CI 0.55, 1.90). For the 611 infants randomised
in these units, there was no difference in death or P/IVH (RR 1.04, 95% CI
0.83, 1.29) and death or grade 3-4 P/IVH (RR 1.12, 95% CI 0.84, 1.49). Lundstrom 2000 reported no infants with periventricular leucomalacia in either group. In the 413 survivors examined, the NNNI 1996 study found no significant difference in periventricular leucomalacia (RR 0.69, 95% CI 0.40, 1.20). The NNNI 1996
study reported long term neurodevelopmental outcome in survivors. There was
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 death or severe disability
(RR 1.00, 95% CI 0.80, 1.24).
Secondary outcomes: The NNNI 1996 study found no significant difference in the rates of treatment failure for a subgroup of infants born 1990-91 (hypotension: RR 0.55, 95% CI 0.24, 1.28) or in transient renal impairment (data not given in paper). Ekblad 1991 (2 infants lost from analysis) found an increase in PDA of borderline significance (RR 1.62, 95% CI 1.00, 2.62; RD 0.33. 95% CI 0.05, 0.61). Beverley 1985 found no difference in PDA (RR 1.14, 95% CI 0.53, 2.48). Meta-analysis of the two studies found no significant difference in PDA (RR 1.39, 95% CI 0.91, 2.14). There was no significant difference in rates of pneumothorax, necrotising enterocolitis, or sepsis. One study (Lundstrom 2000) found a non-significant trend for volume to increase left ventricular output (mean difference 26.6 mls/kg/min, 95% CI -1.7, 69.9) and cerebral blood flow (MD 7.8 mls/kg/min, 95% CI -19.8, 35.4) compared to a control group, but to have little effect on mean blood pressure (MD 6.8 mmHg, 95% CI -16.8, 30.4). No data were available for incidence of low blood flow, use of additional inotropes or retinopathy. In a separate cost comparison also in abstract form, Lynch 2002 reported no significant difference in drug and nursing costs for infants given albumin compared to normal saline.
SUBGROUP ANALYSES ACCORDING TO TYPE OF VOLUME USED:
No studies were found that compared early red cell transfusion to a control group. No study reported any primary outcomes for the comparison of albumin and fresh frozen plasma.
1) COLLOID VERSUS CRYSTALLOID
Primary outcomes: Two studies (So 1997; Lynch 2002)
compared volume expansion using albumin 5% to normal saline 10mls/kg in hypotensive
preterm infants. One study of 63 hypotensive preterm infants (So 1997)
reported no significant difference in mortality (RR 1.36, 95% CI 0.48, 3.82),
any P/IVH (RR 1.52, 95% CI 0.68, 3.42) and grade 3-4 P/IVH (RR 1.61, 95%
CI 0.42, 6.19). No data were available for periventricular leucomalacia or
long term disability.
Secondary outcomes: One study reporting outcomes of 102 infants in abstract form (Lynch 2002), reported a significant reduction in treatment failure (persistent hypotension requiring inotropes: RR 0.54, 95% CI 0.30, 0.96) in infants receiving albumin compared to normal saline. So 1997 reported no significant difference in treatment failure (RR 1.02, 95% CI 0.68, 1.55). Meta-analysis of these two studies found no significant difference in treatment failure (typical RR 0.75, 95% CI 0.53. 1.06). The test of heterogeneity was of borderline significance (p = 0.07). So 1997 reported no significant difference in rates of chronic lung disease (oxygen requirements at 28 days or 36 weeks 'postconception'), patent ductus arteriosus, necrotising enterocolitis and sepsis did not differ significantly. No data were available for retinopathy.
Other outcomes: Lynch 2002 reported a significantly greater increase in mean BP in infants receiving albumin compared to normal saline (MD 9.9%, 95% CI 1.22-18.58). Lynch 2002 reported no significant difference in urine output ([mean +\- standard error] 1.7 +\- 0.3 versus 1.8 +\- 0.3 mls/kg/hr), need for a second bolus of volume (59.2 +\- 7.0% versus 64.2 +\- 6.4%) or cost of therapy including pharmacy and nursing costs ($US52.71 +\- 7.4 versus $US59.72 +\- 7.7). So 1997 reported no significant difference in mean arterial blood pressure (data presented in article in figure) but infants who received albumin received a significantly increased amount of extra volume for hypotension (mean 27.5 versus 10.0 mls, p = 0.02) and had a significantly greater increase in weight in the first 48 hours (5.9 +\- 1.9% versus 0.9 +\- 1.7%, p = 0.05).
2) ALBUMIN VERSUS NO TREATMENT
Primary outcomes: One study randomised 25 normotensive preterm infants to albumin 20% 15 mls/kg or no treatment (Lundstrom 2000)
and found no significant difference in mortality (RR 0.92, 95% CI 0.23, 3.72)
and no periventricular leucomalacia in either group.
Secondary outcomes: Infants receiving albumin had a trend to increased
left ventricular output and cerebral blood flow, with little change in mean
blood pressure (see above). No other outcome data are available.
3) ALBUMIN VERSUS SALINE
See 'Colloid versus crystalloid'.
4) FRESH FROZEN PLASMA VERSUS NO TREATMENT
Primary outcomes: Four studies randomised infants to fresh frozen plasma or no treatment (Beverley 1985; Ekblad 1991; Gottuso 1976; NNNI 1996). Meta-analysis of 3 studies reporting mortality data (Beverley 1985; Gottuso 1976; NNNI 1996) involving a total of 654 infants found no significant difference in mortality (RR 1.05, 95% CI 0.81, 1.36). Two studies (Beverley 1985; Ekblad 1991) reported data on all infants randomised. Beverley 1985 found a significant reduction in P/IVH (RR 0.46, 95% CI 0.21, 0.98) whereas Ekblad 1991
found no significant difference (RR 1.21, 95% CI 0.31, 4.71). Meta-analysis
of these 2 studies found a non-significant trend to reduced P/IVH in infants
receiving volume (RR 0.58, 95% CI 0.30, 1.11; RD -0.14, 95% CI -0.29, 0.01).
One study, Beverley 1985 found a non-significant
trend to less P/IVH grade 3-4 (RR 0.55, 95% CI 0.21, 1.47), reduced death
or P/IVH of borderline significance (RR 0.55, 95% CI 0.30, 1.03; RD -0.21,
95% CI -0.42, -0.01) and no significant difference in death or grade 3-4
P/IVH (RR 0.68, 95% CI 0.32, 1.46). From units with routine scan facilities,
the NNNI 1996 study reported no difference in
P/IVH in survivors examined (RR 1.20, 95% CI 0.83, 1.74), grade 2-4 P/IVH
in survivors examined (RR 0.93, 95% CI 0.45, 1.95), death or P/IVH (RR 1.06,
95% CI 0.83, 1.37), death or grade 3-4 P/IVH (RR 1.01, 95% CI 0.72, 1.41)
and periventricular leucomalacia in survivors (RR 0.76, 95% CI 0.40, 1.45).
Rates of severe disability (RR 0.80, 95% CI 0.48, 1.34), death or severe
disability (RR 0.94, 95% CI 0.73, 1.22) and cerebral palsy (RR 0.79, 95%
CI 0.46, 1.34) were not significantly different.
Secondary outcomes: The NNNI 1996 study found no significant difference in the rate of treatment failure in infants born 1990-91 (hypotension: RR 0.71, 95% CI 0.27, 1.82). No data on the effect on blood flow were available. In the NNNI 1996 study, necrotising enterocolitis was significantly reduced (RR 0.22, 95% CI 0.06, 0.74) in infants receiving fresh frozen plasma, but sepsis significantly increased (RR 1.65, 95% CI 1.13, 2.40). Ekblad 1991 found an increase in PDA of borderline significance (RR 1.62, 95% CI 1.00, 2.62: RD 0.33, 95% CI 0.05, 0.61). Beverley 1985 found no difference in PDA (RR 1.14, 95% CI 0.53, 2.48). Meta-analysis of these two studies found no significant difference in PDA (RR 1.39, 95% CI 0.91, 2.14). No significant difference was found in the rates pneumothorax. The NNNI 1996 study found no significant difference in the rate of renal impairment (data not given in paper) and Ekblad 1991 found no significant difference in creatinine clearance and urinary fractional sodium excretion in the first 5 days of life.
5) ALBUMIN VERSUS FRESH FROZEN PLASMA
One trial involving 20 infants in each group with a systolic BP <
40 mmHg compared fresh frozen plasma to albumin 4.5% 15 mls/kg (Emery 1992).
No significant difference in change in mean blood pressure was found. Both
these groups had a significantly greater increase in mean blood pressure
than a control group who received albumin 20% 5 mls/kg. No difference in
duration of ventilation was found. No other clinical data were available.
6) GELATIN-BASED PLASMA SUBSTITUTE VERSUS NO TREATMENT
Primary outcomes: One study involving 519 infants compared a gelatin-based plasma substitute 20 mls/kg with no treatment (NNNI 1996).
No significant differences were found in mortality (RR 1.22, 95% CI 0.86,
1.72). In a subgroup of infants from centres with routine scanning facilities
there was no significant difference found in P/IVH in survivors (RR 0.89,
95% CI 0.58, 1.34), grade 2-4 P/IVH in survivors (RR 1.12, 95% CI 0.56, 2.27),
death or P/IVH (RR 1.01, 95% CI 0.78, 1.30), death or grade 3-4 P/IVH (RR
1.23, 95% CI 0.90, 1.68) or periventricular leucomalacia in survivors (RR
0.62, 95% CI 0.31, 1.24). Rates of severe disability in all survivors (RR
0.79, 95% CI 0.47, 1.33), death or severe disability (RR 1.05, 95% CI 0.82,
1.34) and cerebral palsy in all survivors (RR 0.74, 95% CI 0.42, 1.28) were
not significantly different.
Secondary outcomes: The NNNI 1996 study found no significant differences in the rate of treatment failure in a subgroup of infants born 1990-91 (hypotension: RR 0.40, 95% CI 0.13, 1.25), transient renal impairment, necrotising enterocolitis (RR 1.06, 95% CI 0.52, 2.15) and sepsis (RR 0.93, 95% CI 0.60, 1.44) . No data on the effect on blood flow, patent ductus arteriosus or retinopathy were available.
7) GELATIN-BASED PLASMA SUBSTITUTE VERSUS FRESH FROZEN PLASMA
Primary outcomes: One study involving 519 infants compared a gelatin-based
plasma substitute with fresh frozen plasma 20 mls/kg (NNNI 1996).
No significant difference was found in mortality (RR 1.17, 95% CI 0.83, 1.64).
In a subgroup of infants born in centres with routine scanning facilities,
the rates of P/IVH in survivors (RR 0.74, 95% CI 0.49, 1.10), grade 2-4
P/IVH in survivors (RR 1.20, 95% CI 0.58, 2.50), death or P/IVH (RR 0.95,
95% CI 0.74, 1.21), death or grade 3-4 P/IVH (RR 1.22, 95% CI 0.89, 1.67)
and periventricular leucomalacia in survivors (RR 0.81, 95% CI 0.38, 1.72)
were similar. Rates of severe disability in all survivors (RR 0.99, 95% CI
0.57, 1.72), death or severe disability (RR 1.11, 95% CI 0.86, 1.43) and
cerebral palsy in all survivors (RR 0.94 95% CI 0.52, 1.69) were not significantly
different.
Secondary outcomes: The NNNI 1996 study found no significant difference in the rate of treatment failure in a subgroup of infants born 1990-91 (hypotension: RR 0.56, 95% CI 0.17, 1.90), or for transient renal impairment. The rate of necrotising enterocolitis was significantly higher (RR 4.92, 95% CI 1.44, 16.80) and sepsis significantly lower (RR 0.57, 95% CI 0.39, 0.83) in infants who received the gelatin based plasma substitute. No data on the effect on blood flow or rates of patent ductus arteriosus and retinopathy were available.
8) BLOOD TRANSFUSION
No randomised study was found that compared early red cell transfusion to control.
OTHER SUBGROUP ANALYSES
1) According to timing of treatment (data not in MetaView tables):
Volume versus no treatment: Early treatment (< 24 hours age): Four
studies with gave volume expansion to infants within the first 24 hours of
life (Beverley 1985; Ekblad 1991; Gottuso 1976; NNNI 1996). Meta-analysis of three studies with data on mortality for 915 infants (Beverley 1985; Gottuso 1976; NNNI 1996)
found no significant difference (RR 1.11, 95% CI 0.88, 1.41). All other outcomes
are as for the comparison 'volume versus no treatment'.
Colloid (5% albumin) versus crystalloid (normal saline): Early treatment (<24hours): One study (So 1997) enrolled infants with hypotension at <2 hours of age and reported no significant difference in mortality (RR 1.36, 95% CI 0.48, 3.82), any P/IVH (RR 1.52, 95% CI 0.68, 3.42) and grade 3-4 P/IVH (RR 1.61, 95% CI 0.42, 6.19). So 1997 reported no significant difference in treatment failure (RR 1.02, 95% CI 0.68, 1.55), rates of chronic lung disease (oxygen requirements at 28 days or 36 weeks 'postconception'), patent ductus arteriosus, necrotising enterocolitis and sepsis. The other study (Lynch 2002) comparing albumin with normal saline enrolled hypotensive infants <3 days of age.
2) According to types of infants enrolled:
a) Unselected preterm infants (not selected on the basis of cardiovascular
compromise): All studies that compared volume to no treatment enrolled infants
on the basis of gestation or birthweight. See comparison of volume versus
no treatment.
b) Infants with clinical evidence of cardiovascular compromise: Three studies enrolled infants with clinical evidence of cardiovascular compromise. Emery 1992 enrolled hypotensive infants (systolic blood pressure < 40 mmHg) to fresh frozen plasma 15 mls/kg or albumin 4.5% 15 mls/kg. A control group received albumin 20% 5 mls/kg. Lynch 2002 enrolled hypotensive preterm infants (mean BP <5th percentile according to Vermsold criteria) to 5% albumin versus normal saline 10mls/kg. So 1997 enrolled hypotensive infants with a low mean blood pressure (defined by weight strata) to albumin 10 mls/kg or isotonic saline 10 mls/kg. Only one study (Lynch 2002) reported a significant difference with a significant reduction in treatment failure in infants receiving albumin (RR 0.54, 95% CI 0.30, 0.96) and a significant increase in mean BP (WMD 9.90 mmHg, 9% CI 1.22, 18.58) compared to normal saline. No differences were found for any outcomes (see comparisons of 'fresh frozen plasma versus albumin' and 'colloid versus crystalloid'). No studies were found that compared volume to no treatment in infants with cardiovascular compromise.
c) Infants with low blood flow: No studies were found that compared volume to no treatment in infants with low blood flow.
HETEROGENEITY
No statistically significant heterogeneity was found for any analysis
included in this review. Comparing volume to no treatment: One small study
(Beverley 1985) found a reduced rate of P/IVH. The other studies (Ekblad 1991; NNNI 1996)
and the overall meta-analysis did not support a difference in P/IVH, high
grade P/IVH or subsequent disability. Comparing albumin to normal saline:
One study (Lynch 2002) reported a significant
reduction in treatment failure and significantly greater increase in mean
BP in hypotensive infants receiving albumin in the first 3 days. The other
study (So 1997) reported no significant difference
in treatment failure and no significant difference in % change in mean BP
in infants enrolled <2 hours age.
SENSITIVITY ANALYSIS ACCORDING TO METHODOLOGICAL QUALITY (data not in MetaView tables)
The results of this review are not sensitive to excluding the study that
did not state whether there was adequate allocation concealment (Ekblad 1991). Only one study stated that the interventions were blinded in any way (Lynch 2002)
and this study compared 5% albumin with normal saline 10mls/kg in hypotensive
infants in the first 3 days after birth. This study reported a significantly
greater increase in mean BP in infants receiving albumin compared to normal
saline (MD 9.9 mmHg, 95% CI 1.22, 18.58) but no significant difference in
urine output (MD -0.10 mls/kg/hr, -0.93, 0.73). Comparing volume with no
treatment, one study with results for P/IVH had incomplete head ultrasound
data at 6 weeks (NNNI 1996). Two studies had complete follow up of infants for P/IVH (Beverley 1985; Ekblad 1991)
and found a non-significant trend to reduced P/IVH (RR 0.6, 95% CI 0.3, 1.1;
RD -0.14, 95% CI -0.29, 0.01) and grade 3-4 P/IVH (RR 0.6, 95% CI 0.2, 1.5;
RD -0.11, 95% CI -0.27, 0.06) in infants receiving volume. No significant
difference for combined death or P/IVH (RR 0.95, 95% CI 0.74, 1.21) was found.
The NNNI 1996 study had complete follow up for
neurodevelopmental outcomes reporting 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 death or severe disability (RR 1.00, 95% CI 0.80, 1.24).
Two studies were excluded from the analyses as insufficient volume (less than 10mls/kg) was given (Bland 1976; Greenough 1993) and the mean age of infants was > 32 weeks (Bland 1976). One study (Emery 1992) had data excluded from a subgroup of infants who received insufficient volume and did not meet the criteria for controls (given albumin 20% 5 mls/kg). These data do not meet inclusion criteria for this review. The excluded data from the study by Emery 1992 are given in 'results' in the comparison of 'fresh frozen plasma versus albumin'. The inclusion of data from any of these comparisons has minimal impact on any of the estimates made in this review.
This review examines evidence from randomised controlled trials for the use of early volume expansion in very preterm infants. In subgroup analysis it looks for evidence for the use of different types of volume expansion and for the use of volume expansion in different types of infants. The analysis had a power of 80% to detect a 9% absolute difference in rates of combined death and severe disability between volume and control groups at the 5% significance level. Six of the 7 trials reported adequate randomisation procedures and allocation concealment. Only one reported efforts to blind caregivers with this study comparing use of albumin with normal saline in hypotensive infants (Lynch 2002). Only one trial provided data on long term neurodevelopment (NNNI 1996). This was the largest trial with no losses to follow up and blinded assessment of neurodevelopment at 2 years, including the Griffiths' Scales of Mental Development and clinical examination. This trial had incomplete ascertainment of head ultrasound findings in a subgroup of infants born in centres with routine scan facilities. The studies with complete ascertainment of head ultrasound abnormalities are much smaller (Beverley 1985; Ekblad 1991).
The studies comparing volume to no treatment did not enrol infants with evidence of cardiovascular compromise. Infants were predominantly enrolled on the basis of gestation or birthweight. However, by virtue of their gestation or birthweight these infants were at risk of mortality, P/IVH and disability. Whether these infants had hypovolaemia was not measured. The studies that did enrol infants on the basis of cardiovascular compromise enrolled infants on the basis of low blood pressure and compared different forms of volume expansion. They did not have a control group that received no treatment. Blood flow (left ventricular output and cerebral blood flow) was measured by only one study (Lundstrom 2000). This study enrolled infants with stable cardiovascular status and normal mean blood pressure who had not received volume or inotropes in the preceding 3 hours. There is no data on blood flow in infants with cardiovascular compromise.
There is no evidence to support the routine use of volume expansion given to very preterm infants on the basis of gestational age or birthweight in the first days of life. There is no evidence that routine early volume expansion decreases the incidence of cardiovascular compromise (hypotension) or mortality. Evidence from one study of a reduced rate of P/IVH is not supported by the overall meta-analysis or any other study. No difference was seen in the rates of higher grade cerebral ischaemic lesions or subsequent disability. The observations from one study that infants who received fresh frozen plasma had a lower incidence of necrotising enterocolitis and higher incidence of sepsis should be treated with caution. The overall rate of mortality and disability were not different between infants who received fresh frozen plasma compared to no treatment in this study.
One study (Lynch 2002) reported a significant reduction in treatment failure (persistent hypotension) and a greater increase in mean BP in infants with hypotension treated with albumin compared to normal saline. Other clinical outcomes including mortality and P/IVH were not reported. The other study (So 1997) and the overall meta-analysis do not support a reduction in rate of treatment failure or change in mean BP, and there was no significant difference in mortality, P/IVH or other clinical outcomes. Differences between the studies identified in subgroup analyses included the different timing of intervention (Lynch 2002 enrolled infants < 3 days age and So 1997 enrolled infants <2 hours age) and the lack of blinding of treatment in one study (So 1997). The full publication of the study by Lynch 2002 is awaited. One study (NNNI 1996) reported no significant difference in mortality, P/IVH or disability in infants who received a gelatin-based plasma substitute compared to fresh frozen plasma. No data were available for the use of early blood transfusion. Data for the use of albumin compared to no treatment are only available from one small study with inadequate power to demonstrate any benefit and enrolling infants with a stable cardiovascular status.
None.
| Study | Methods | Participants | Interventions | Outcomes | Notes | Allocation concealment |
| Beverley 1985 | Adequate randomisation: yes, sealed envelopes. Allocation concealment: yes. Blinding of intervention: no. Blinding of measurement: yes. Losses to follow up: yes, 7 (9%) infants excluded from study due to death (1), intraventricular hemorrhage on admission (1) and treatment of hypotension or coagulopathy with fresh frozen plasma (5 controls). Data available for mortality and intraventricular haemorrhage in excluded infants. | Infants < 1550g or < 32 weeks. Mean gestation: Treatment group: 29.4 weeks (sd 2.4); Control: 28.8 (sd 2.1). Mean birthweight: Treatment group: 1246g (sd 400); Control: 1216g (sd 320). | Intervention (n = 38): fresh frozen plasma 10 mls/kg on admission and 24 hours of age. Control (n = 42): no treatment. | Stated primary outcome: P/IVH. Other outcomes: mortality, respiratory distress syndrome, ventilation, pCO2 > 7kPa, pH < 7.15, mean maximal peak inspiratory pressure, mean maximal inspired oxygen, pneumothorax, patent ductus arteriosus, coagulation studies and platelet counts. | A | |
| Ekblad 1991 | Adequate randomisation: method not stated. Allocation concealment: unclear. Blinding of intervention: no. Blinding of measurement: no. Losses to follow up: yes. Outcomes reported for 38 of 40 infants in one paper (PDA) and 35 of 40 (renal function) in the other. Data for P/IVH and mortality for the excluded infants is available and used in the analysis of these outcomes. | Appropriate for gestational age preterm infants stratified by gestation: < 30 weeks (n = 19), 30-34, weeks (n = 19). < 5 hours of age. Mean gestation: 27.8 (sd 1.7); Control: 27.6 (sd 1.6). Mean birthweight: Treatment: 1375g. Control: 1448g. | Intervention (n = 21): Fresh frozen plasma 10 mls/kg over 2 hours, daily for 3 days, no additional sodium. Control (n = 19): no treatment, sodium added to fluids. | Stated primary outcome: water balance and extracellular volume (bromide space), renal function. Other outcomes: ventilatory assistance, respiratory distress syndrome, patent ductus arteriosus, P/IVH. | Data for grade of P/IVH in excluded infants requested from author. | B |
| Emery 1992 | Adequate randomisation: yes, sealed envelope. Allocation concealment: yes. Blinding of intervention: no. Blinding of measurement: no. Losses to follow up: none. | Preterm infants day 1-4 (23-35 weeks, (552-1954g), hypotension with systolic BP < 40 mmHg. Exclusions: clinical fluid overload. Median gestation: Group 1: 26 weeks (range 23-34); Group 2: 27 weeks (range 24-25). Median birthweight: Group 1: 958g (566-1880). Group 2: 844g (690-1954). | Intervention: Group 1 (n = 20) fresh frozen plasma 15 mls/kg over 3 hours. Group 3 (n = 20) 4.5% albumin 15 mls/kg over 3 hours. | Stated primary outcome: systolic blood pressure one and 4 hours after infusions. Other outcomes: none. | No data available for inclusion in meta-analysis. Median change blood pressure available. | A |
| Gottuso 1976 | Two centres. Adequate randomisation: yes, used sealed envelopes. Allocation concealment: yes. Blinding of intervention: no. Blinding of measurement: no. Losses to follow up: none. | Stratified into 3 groups: Group A; birth weight 700-1000g, < 24 hours age. Group B: 1001-2000g, severe respiratory distress syndrome, < 24 hours age. Group C: > 1000g, any age, partial thromboplastin time > 60 secs, and acidosis or hypoxia in 60% inspired oxygen. | Intervention: Supportive care and fresh frozen plasma 15 mls/kg (n = 26). Control: supportive care only (n = 33). | Stated primary outcome: none stated. Other outcomes: mortality, pH, pCO2, FiO2/PaO2, intracranial and pulmonary haemorrhage. | Infants randomised to exchange transfusion excluded from review. Group A and B infants received treatment at mean age 7.4 to 12 hours. Group C median age 20 hours. | A |
| Lundstrom 2000 | Adequate randomisation: yes, sealed envelopes. Allocation concealment: yes. Blinding of intervention: no. Blinding of measurement: not stated. Losses to follow up: none. | Preterm
infants < 33 weeks (median 28, range 25-32), arterial line, mean arterial
BP 29 to 40 mmHg, normal blood glucose, no volume or inotrope support within
preceding 3 hours. Mean postnatal age = 31.8 hrs (range 5-224). Mean gestation: Intervention: 27.9 weeks; Control: 28.7 weeks Mean birthweight: Intervention: 1134g; Control: 1238g. | Intervention (n = 13): albumin 20% 15 mls/kg. Control (n = 12): no treament. | Stated primary outcome: mean arterial BP, left ventricular output, global cerebral blood flow. Other outcomes: mortality, P/IVH, periventricular leucomalacia not available according to treatment groups. | Data from publication used. Clinical data for mortality obtained from author. | A |
| Lynch 2002 | Single centre. Adequate randomisation: yes, method not reported. Allocation concealment: yes. Blinding of intervention: yes. Blinding of measurement: yes. Losses to follow up: unclear. | Infants
<= 3 days age, mean arterial pressure <5th percentile by Versmold criteria
for >10 minutes and parental permission. Infants mean weight 1560g +/- 78g, gestation 30 +/- 0.4 weeks. | 5% albumin 10mls/kg infused over 20 minutes (n = 49). Normal saline 10mls/kg infused over 20 minutes (n = 53). Volume repeated if failure of response. Treatment success defined as resolution of hypotension. | Primary outcomes: % change in blood pressure. Other outcomes: urine output, use of second bolus of volume, use of pressure support, average cost of treatment, average amount of nursing time required for preparation of drug. Treatment failure defined as need for pressor support for persisting hypotension (mean BP<5th percentile). | Published in abstract form only. | A |
| NNNI 1996 | Multicentre. Adequate randomisation: yes, central telephone randomization using minimization. Allocation concealment: yes. Blinding of intervention: no. Blinding of measurement: yes. Losses to follow up: none for death and disability, incomplete head ultrasound data (in units with routine scanning - 84% for 6 weeks survivors). | Infants
< 32 weeks, < 2 hours old and clinician uncertain as to whether to
use volume, no indications or contraindications to any of the interventions. Median gestation: 29 weeks (range 27-31) Median birthweight (interquartile range): Group 1: 1265g (981-1543); Group 2: 1254g (965-1535); Control: 1240g (980-1510). | Intervention: Group 1 ( n = 257). Fresh frozen plasma 20 mls/kg over 15 mins, 10 mls/kg 24hrs later. Group 2 (n = 261). Gelatin-based plasma substitute (Gelofusine) 20 mls/kg over 15 mins, 10 mls/kg 24hrs later. Control (n = 258): Maintenance fluids 60-120 mls/kg/day. Other management according to local physician. | Stated primary outcome: death before discharge or severe disability at 2 years. Other outcomes: P/IVH on 1 and 6 week ultrasound. | 77% of eligible infants enrolled. P/IVH data taken from units with routine scanning only. Data for reclassified P/IVH and periventricular leucomalacia requested from author. | A |
| So 1997 | Adequate randomisation: yes, computer used. Allocation concealment: yes. Blinding of intervention: no. Blinding of measurement: no. Losses to follow up: none. | Infants
< 34 weeks, birthweight < 2000g, mechanically ventilated for RDS, hypotension
(MAP < 25, 30, 35 mmHg at < 1kg, 1-1.49 kg, 1.5-1.99 kg respectively)
at < 2 hours age, no previous fluids or inotropes. Exclusions: infants of mothers given antihypertensives within 24 hours of birth, severe congenital anomalies, cyanotic heart disease or left ventricular outflow anomalies Mean gestation: Intervention group: 28.1 weeks (sd 4.0); Control: 28.5 weeks (sd 2.8). Mean birthweight: Intervention: 1123g (sd 458); Control: 1163g (sd 367). | Intervention (n = 32): 5% albumin 10 mls/kg over 30 mins up to 3 doses. Control (n = 31): isotonic saline 10 mls/kg over 30 mins up to 3 doses. | Stated primary outcome: treatment failure (persistent hypotension requiring dopamine). Other outcomes: need for extra volume, weight gain, urine output, serum sodium, patent ductus (echo confirmed), P/IVH (ultrasound at 2 and 6 days and 3 weeks), necrotising enterocolitis, chronic lung disease (oxygen at 28 days and 36 weeks post conception), and mortality. | A |
| Study | Reason for exclusion |
| Alexander 1976 | Fresh frozen plasma versus no treatment. Printed in abstract form only. Volume of fresh frozen plasma not stated. No clinical data could be extracted for inclusion in review. |
| Alkalay 1999 | No control group. |
| Andrew 1993 | Randomised trial of platelet transfusion in thrombocytopenic newborns. |
| Barr 1977 | No control group. |
| Bauer 1993 | No control group. |
| Beeram 2003 | Randomised trial of two different volumes of packed red cell transfusions in haemodynamically stable very low birth weight infants. |
| Bell 1980 | Randomised trial of higher and lower fluid intakes. |
| Bignall 1989 | No control group. |
| Bland 1976 | Insufficient volume to meet inclusion criteria. Mean age of infants > 32 weeks. Randomised preterm infants < 37 weeks with serum protein < 4.6 g% to receive glucose versus albumin 25% 8 mls/kg within 2 hours of birth. |
| Blank 1984 | Randomized to red cell transfusion to maintain Hb > 10 g/L or control group. Intervention predominantly late. |
| Chan 1976 | Randomised to albumin 1g/kg versus no treatment prior to exchange transfusioin. |
| Costarino 1992 | Randomised trial of higher and low sodium intake. |
| Delivoria 1976 | Used alternation to assign infants to exchange transfusion or control. |
| Dimitriou 2001 | No control group. Observed effect of albumin infusion on BP, pH and core-peripheral temperature difference. |
| Dixon 1999 | Randomised trial of 10mls/kg 4.5% albumin versus 4.2% sodium bicarbonate in acidotic newborn infants. Gestations not reported. Infants with hypotension or evidence of acute blood loss excluded. |
| Ekblad 1987 | Randomised to high and low sodium intake. |
| Greenough 1993 | Given inadequate volume: 20% albumin 5 mls/kg given at maintenance fluid rate instead of maintenance fluids. Placebo was maintenance fluids. |
| Gurkan 2000 | Randomised trial of 20% albumin in term newborns with perinatal asphyxia. |
| Hosono 2001 | Randomised trial of albumin infusion in term infants with non-haemolytic hyperbiliruninaemia. |
| Kanarek 1991 | Randomised after 48-72 hours of age to addition of albumin to total parenteral nutrition. |
| Kavvadia 2000 | Trial of fluid restriction. |
| Lambert 1998 | No control group. |
| Lay 1980 | No control group. |
| Leake 1976 | Infants 3 to 16 days age. Infants randomly assigned to different infusion rates of maintenance fluids. |
| Meyer 1993 | Randomised to packed red cell transfusion to maintain hematocrit > 0.35 or control. Mean time of transfusion 28 days |
| Nelle 1997 | Enrolled preterm infants with anaemia. Studied effect of blood transfusion. No control group. |
| Nose 1996 | Infants < 4 days old excluded. Randomised study of 2 different infusion rates of red cell transfusion. |
| Oca 2003 | Enrolled 50 newborn infants with hypotension in first 24 hours. Stratified randomisation of infants <2500g and >=2500. Excluded because of excessive post randomisation losses (9/39 =23%) for infants <2500g. |
| Papile 1978 | Observational study of effects of sodium bicarbonate in acidotic infants. |
| Pladys 1994 | No control group. |
| Pladys 1997 | No control group. |
| Sinclair 1968 | Infants randomised to varying oxygen, alkali (rapid infusion of sodium bicarbonate) and ventilation strategies. |
| Sriram 1997 | No control group. |
| Stoddart 1996 | Enrolled neonates undergoing major surgery. They were excluded if the body weight was less than 2kg. |
| Warburton 1983 | Randomised to different volumes of maintenance fluids. |
| Weisman 1992 | Randomised infants with early onset sepsis to 10mls/kg intravenous immunoglobulin or albumin. |
| Wirth 1979 | Control group received bicarbonate. Crossover study of bicarbonate and albumin. Gestational ages of infants not stated. Printed in abstract form only. |
Beverley DW, Pitts-Tucker TJ, Congdon PJ, Arthur RJ, Tate G. Prevention of intraventricular haemorrhage by fresh frozen plasma. Arch Dis Child 1985;60:710-3.
Ekblad 1991 {published data only}
* Ekblad H, Kero P, Korvenranta H. Renal function in preterm infants during the first five days of life: influence of maturation and early colloid treatment. Biol Neonate 1992;61:308-17.
Ekblad H, Kero P, Shaffer SG, Korvenranta H. Extracellular volume in preterm infants: influence of gestational age and colloids. Early Hum Dev 1991;27:1-7.
Emery 1992 {published data only}
Emery EF, Greenough A, Gamsu HR. Randomised controlled trial of colloid infusions in hypotensive preterm infants. Arch Dis Child 1992;67:1185-8.
Gottuso 1976 {published data only}
Gottuso MA, Williams ML, Oski FA. The role of exchange transfusion in the management of low-birth-weight infants with and without severe respiratory distress syndrome. J Pediatr 1976;89:279-85.
Lundstrom 2000 {published data only}
* Lundstrom K, Pryds O, Greisen G. The haemodynamic effects of dopamine and volume expansion in sick preterm infants. Early Hum Dev 2000;57:157-3.
Lundstrom KE. A randomized, controlled study of the influence of dopamine and volume expansion on CBF, LVO and MABP in hypotensive, preterm, infants. In: Proceedings of 14th European Congress of Perinatal Medicine, Helsinki, Finland. 1994:500.
Lynch 2002 {unpublished data only}
* Lynch SK, Stone CS, Graeber J, Polak MJ. Colloid vs. cystalloid therapy for hypotension in neonates. In: Pediatr Res. Vol. 51. 2002:384A.
Mullett MD, Lynch SK, Graeber JE, Stone C, Polak MJ. Cost comparison of albumin (ALB) versus cormal saline (NS) therapy for hypotension in neonates. In: Pediatr Res. Vol. 51. 2002:370A.
NNNI 1996 {published data only}
Fooks J, Fritz S, Tin W, Yudkin P, Johnson A, Elbourne D, Hey E. A comparison of two methods of follow-up in a trial of prophylactic volume expansion in preterm babies. Paediatr Perinat Epidemiol 1998;12:199-216.
Fooks J, Mutch L, Yudkin P, Johnson A, Elbourne D. Comparing two methods of follow up in a multicentre randomised trial. Arch Dis Child 1997;76:369-76.
* The Northern Neonatal Nursing Initiative [NNNI] Trial Group. Randomized trial of prophylactic early fresh-frozen plasma or gelatin or glucose in preterm babies: outcome at 2 years. Lancet 1996;348:229-32.
The Northern Neonatal Nursing Initiative [NNNI] Trial Group. A randomized trial comparing the effect of prophylactic intravenous fresh frozen plasma, gelatin or glucose on early mortality and morbidity in preterm babies. Eur J Pediatr 1996;155:580-8.
So KW, Fok TF, Ng PC, Wong WW, Cheung KL. Isotonic saline vs 5% albumin as volume expander. In: Pediatr Res. Vol. 39. 1996:246A.
* So KW, Fok TF, Ng PC, Wong WW, Cheung KL. Randomised controlled trial of colloid or crystalloid in hypotensive preterm infants. Arch Dis Child 1997;76:F43-6.
Alexander G, Visveshwara N, and Bauer CR. Prophylactic exchange transfusion in the very low birth weight infant. Pediatr Res 1976;10:420.
Alkalay 1999 {published data only}
Alkalay AL, Galvis S, Ferry DA, Sola A. Packed red blood cell transfusions do not modify cardiac function of premature infants with "very low hematocrits". Pediatr Res 1999;45:261A.
Andrew 1993 {published data only}
Andrew M, Vegh P, Caco C, Kirpalani H, Jefferies A, Ohlsson A, Watts J, Saigal S, Milner R, Wang E. A randomized, controlled trial of platelet transfusions in thrombocytopenic premature infants. J Pediatr 1993;123:285-91.
Barr 1977 {published data only}
Barr PA, Bailey PE, Sumners J, Cassady G. Relation between arterial blood pressure and blood volume and effect of infused albumin in sick preterm infants. Pediatrics 1977;60:282-9.
Bauer 1993 {published data only}
Bauer K, Linderkamp O, Versmold HT. Short-term effects of blood transfusion on blood volume and resting peripheral blood flow in preterm infants. Acta Paediatr 1993;82:1029-33.
Beeram 2003 {unpublished data only}
Beeram MR, Ginther S, Olvera R, Loughran C. Safety and efficacy of high volume (20cc/kg) vs low volume (15cc/kg) packed red blood cell transfusions (PRBCTs) in very low birthweight infants (VLBW): double blinded randomized study. Pediatr Res 2003;53:A2063.
Bell 1980 {published data only}
Bell EF, Warburton D, Stonestreet BS, Oh W. High-volume fluid intake predisposes premature infants to necrotising enterocolitis. Lancet 1979;2 (8133):90.
* Bell EF. Warburton D, Stonestreet BS, Oh W. Effect of fluid administration on the development of symptomatic patent ductus arteriosus and congestive heart failure in premature infants. NEJM 1980;302:598-604.
Bignall 1989 {published data only}
Bignall S, Bailey PC, Bass CA, Cramb R, Rivers RP, Wadsworth J. The cardiovascular and oncotic effects of albumin infusion in premature infants. Early Hum Dev 1989;20:191-201.
Bland 1976 {published data only}
Bland RD, Clarke TL, Harden LB. Rapid infusion of sodium bicarbonate and albumin into high-risk premature infants soon after birth: a controlled, prospective trial. Am J Obst Gyn 1976;124:363-7.
Blank 1984 {published data only}
Blank JP, Sheagren TG, Vajaria J, Mangurten HH, Benawra RS, Puppala BL. The role of RBC transfusion in the premature infant. Am J Dis Child 1984;138:831-3.
Chan 1976 {published data only}
Chan G, Schiff D. Variance in albumin loading in exchange transfusions. J Pediatr 1976;88:609-13.
Costarino 1992 {published data only}
Costarino AT Jr, Gruskay JA, Corcoran L, Polin RA, Baumgart S.. Sodium restriction versus daily maintenance replacement in very low birth weight premature neonates: a randomized, blind therapeutic trial. J Pediatr 1992;120:88-106.
Delivoria 1976 {published data only}
Delivoria-Papadopoulos M, Miller LD, Forster RE, Oski FA. The role of exchange transfusion in the management of low-birth-weight infants with and without severe respiratory distress syndrome. J Pediatr 1976;89:273-8.
Dimitriou 2001 {published data only}
Dimitriou G, Greenough A, Mantagos J, Skinner S. Metabolic acidosis, core-peripheral temperature difference and blood pressure response to albumin infusion in hypotensive, very premature infants. J Perinat Med 2001;29:442-5.
Dixon 1999 {published data only}
Dixon H, Hawkins K, Stephenson T. Comparison of albumin versus bicarbonate treatment for neonatal metabolic acidosis. Eur J Pediatr 1998;158:414-5.
Ekblad 1987 {published data only}
Ekblad H, Kero P, Takala J, Korvenranta H, Valimaki I. Water, sodium and acid-base balance in premature infants: therapeutical aspects. Acta Paediatr Scand 1987;76:47-53.
Greenough 1993 {published data only}
Greenough A, Emery E, Hird MF, Gamsu HR. Randomised controlled trial of albumin infusion in ill preterm infants. Eur J Pediatr 1993;152:157-9.
Gurkan 2000 {published data only}
Gurkan F, Haspolat K, Yaramis A, Ece A. Beneficial effect of human albumin on neonatal cerebral edema. Am J Ther 2000;8:253-4.
Hosono 2001 {published data only}
Hosono S, Ohno T, Kimoto H, Nagoshi R, Shimizu M, Nozawa M. Effects of albumin infusion therapy on total and unbound bilirubin values in term infants with intensive phototherapy. Pediatr Int 2001;43:8-11.
Kanarek 1991 {published data only}
Kanarek KS, Adamson M, Williams PR, and Blair C. Concurrent administration of albumin with total parenteral nutrition (TPN) in ill newborn infants. In: Pediatr Res. Vol. 29. 1991:1771.
* Kanarek KS, Williams PR, Blair C. Concurrent administration of albumin with total parenteral nutrition in sick newborn infants. J Parenter Enteral Nutr 1992;16:49-53.
Kavvadia 2000 {published data only}
Greenough A, Cheeseman P, Kavvadia V, Dimitriou G, Morton M. Colloid infusion in the perinatal period and abnormal neurodevelopmental outcome in very low birth weight infants. Eur J Pediatr 2000;161:319-23.
* Kavvadia V, Greenough A, Dimitriou G, Hooper R. Randomised trial of fluid restriction in ventilated very low birthweight infants. Arch Dis Child Fetal Neonatal Ed 2000;83:F91-6.
Lambert 1998 {published data only}
Lambert HJ, Baylis PH, Coulthard MG. Central-peripheral temperature difference, blood pressure, and arginine vasopressin in preterm neonates undergoing volume expansion. Arch Dis Child 1998;78:F43-5.
Lay 1980 {published data only}
Lay KS, Bancalari E, Malkus H, Baker R, Strauss J. Acute effects of albumin infusion on blood volume and renal function in premature infants with respiratory distress syndrome. J Pediatr 1980;97:619-23.
Leake 1976 {published data only}
Leake RD, Zakauddin S, Trygstad CW, Fu P, Oh W. The effects of large volume intravenous fluid infusion on neonatal renal function. J Pediatr 1976;89:968-72.
Meyer 1993 {published data only}
Meyer J, Sive A, Jacobs P. Empiric red cell transfusion in asymptomatic preterm infants. Acta Paediatr 1993;82:30-4.
Nelle 1997 {published data only}
Nelle M, Hoecker C, Linderkamp O. Effects of red cell transfusion on pulmonary blood flow and right ventricular systolic time intervals in neonates. Eur J Pediatr 1997;156:553-6.
Nose 1996 {published data only}
Nose Y, Tamai H, Shimada S, Funato M. Haemodynamic effects of differing blood transfusion rates in infants less than 1500 g. J Paediatr Child Health 1996;32:177-82.
Oca 2003 {published data only}
* Oca MJ, Nelson M, Donn SM. Randomized trial of normal saline versus 5% albumin for the treatment of neonatal hypotension. J Perinatol 2003;23:473-6.
Oca MJ, Nelson M, Donn SM. Randomized trial of normal saline (NS) versus 5% albumin (ALB) for the treatment of neonatal hypotension. Pediatr Res 1999;45:215A.
Papile 1978 {published data only}
Papile LA, Burstein J, Burstein R, Koffler H, Koops B. Relationship of intravenous sodium bicarbonate infusions and cerebral intraventricular hemorrhage. J Pediatr 1978;93:834-6.
Pladys 1994 {published data only}
Pladys P, Betremieux P, Lefrancois C, Schleich JM, Gourmelon N, Le Marec B. Doppler echocardiography in the evaluation of volume expansion effects in newborn infants. Arch Pediatr 1994;1:470-6.
Pladys 1997 {published data only}
Pladys P, Wodey E, Betremieux P, Beuchee A, Ecoffey C. Effects of volume expansion on cardiac output in the preterm infant. Acta Paediatr 1997;86:1241-5.
Sinclair 1968 {published data only}
Sinclair JC, Engel K, Silverman WA. Early correction of hypoxemia and acidemia in infants of low birth weight: a controlled trial of oxygen breathing, rapid alkali infusion, and assisted ventilation. Pediatrics 1968;42:565-89.
Sriram 1997 {published data only}
Sriram S, Gizowski K, Ramirez J, Agarwala B, Ruschhaupt D, Meadow W. Hemodynamic consequences of volume infusions in the NICU: What's cardiac output got to do with it? Pediatr Res 1997;41:179A.
Stoddart 1996 {published data only}
Stoddart PA, Rich P, Sury MR. A comparison of 4.5% human albumin solution and Haemaccel in neonates undergoing major surgery. Paediatr Anaesth 1996;6:103-6.
Warburton 1983 {published data only}
Warburton D, Bell EF, Stonestreet BS, Oh W. Echocardiographic effects of high and low volumes of maintenance fluid administration in low-birth-weight infants. Dev Parmacol Ther 1983;6:45-54.
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Weisman LE, Stoll BJ, Kueser TJ, Rubio TT. Frank CG, Heiman HS, Subramanian KN, Hankins CT. Anthony BF, Cruess DF, et al. Intravenous immune globulin therapy for early-onset sepsis in premature neonates. J Pediatr 1992;121:434-43.
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* Wirth FH, Squires P. The treatment of metabolic acidosis (MA) in newborn infants with respiratory distress (RD). A random prospective trial alternating albumin and NaHCO3 infusions in the same infant. Pediatr Res 1979;13:484.
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01.01 Death
01.02 Any P/IVH
01.03 P/IVH grade 2-4
01.04 P/IVH grade 3-4
01.05 Death or P/IVH
01.06 Death or severe P/IVH
01.07 Periventricular leucomalacia in survivors
01.08 Severe neurodevelopmental disability in survivors
01.09 Death or severe neuodevelopmental disability
01.10 Cerebral palsy in survivors
01.11 Failed treatment (hypotension) in infants born 1990-1991
01.12 Patent ductus arteriosus
01.13 Pneumothorax
01.14 Necrotising enterocolitis
01.15 Sepsis
01.16 Change mean BP (%)
01.17 Change left ventricular output (%)
01.18 Change cerebral blood flow (%)
02 Colloid (albumin) versus crystalloid (saline) in hypotensive infants
02.01 Death
02.02 Any P/IVH
02.03 P/IVH grade 3-4
02.04 Failed treatment
02.05 Chronic lung disease
02.06 Patent ductus arteriosus
02.07 Necrotising enterocolitis
02.08 Sepsis
02.09 Change mean BP (%)
03 Albumin versus no treatment in normotensive infants
03.01 Death
03.02 Periventricular leucomalacia in survivors
03.03 Change mean BP (%)
03.04 Change left ventricular output (%)
03.05 Change cerebral blood flow (%)
04 Fresh frozen plasma versus no treatment
04.01 Death
04.02 Any P/IVH
04.03 P/IVH grade 2-4
04.04 P/IVH grade 3-4
04.05 Death or P/IVH
04.06 Death or P/IVH grade 3-4
04.07 Periventricular leucomalacia in survivors examined
04.08 Severe neurodevelopmental disability in survivors
04.09 Death or severe neuodevelopmental disability
04.10 Cerebral palsy in survivors
04.11 Failed treatment (hypotension) in infants born 1990-1991
04.12 Patent ductus arteriosus
04.13 Pneumothorax
04.14 Necrotising enterocolitis
04.15 Sepsis
05 Gelatin versus no treatment
05.01 Death
05.02 Any P/IVH in survivors examined
05.03 P/IVH grade 2-4 in survivors examined
05.04 Death or P/IVH in infants examined
05.05 Death or P/IVH grade 3-4 in infants examined
05.06 Periventricular leucomalacia in survivors examined
05.07 Severe neurodevelopmental disability in survivors
05.08 Death or severe neuodevelopmental disability
05.09 Cerebral palsy in survivors
05.10 Failed treatment (hypotension) in infants born 1990-1991
05.11 Necrotising enterocolitis
05.12 Sepsis
06 Gelatin versus fresh frozen plasma
06.01 Death
06.02 Any P/IVH in survivors examined
06.03 P/IVH grade 2-4 in survivors examined
06.04 Death or P/IVH in infants examined
06.05 Death or P/IVH grade 3-4 in infants examined
06.06 Periventricular leucomalacia in survivors examined
06.07 Severe neurodevelopmental disability in survivors
06.08 Death or severe neuodevelopmental disability
06.09 Cerebral palsy in survivors
06.10 Failed treatment (hypotension) in infants born 1990-1991
06.11 Necrotising enterocolitis
06.12 Sepsis
| Comparison or outcome | Studies | Participants | Statistical method | Effect size |
|---|---|---|---|---|
| 01 Volume versus no treatment | ||||
| 01 Death | 4 | 940 | RR (fixed), 95% CI | 1.11 [0.88, 1.40] |
| 02 Any P/IVH | RR (fixed), 95% CI | Subtotals only | ||
| 03 P/IVH grade 2-4 | RR (fixed), 95% CI | Subtotals only | ||
| 04 P/IVH grade 3-4 | 1 | 80 | RR (fixed), 95% CI | 0.55 [0.21, 1.47] |
| 05 Death or P/IVH | RR (fixed), 95% CI | Subtotals only | ||
| 06 Death or severe P/IVH | RR (fixed), 95% CI | Subtotals only | ||
| 07 Periventricular leucomalacia in survivors | RR (fixed), 95% CI | Subtotals only | ||
| 08 Severe neurodevelopmental disability in survivors | 1 | 604 | RR (fixed), 95% CI | 0.80 [0.52, 1.23] |
| 09 Death or severe neuodevelopmental disability | 1 | 776 | RR (fixed), 95% CI | 1.00 [0.80, 1.24] |
| 10 Cerebral palsy in survivors | 1 | 604 | RR (fixed), 95% CI | 0.76 [0.48, 1.20] |
| 11 Failed treatment (hypotension) in infants born 1990-1991 | 1 | 644 | RR (fixed), 95% CI | 0.55 [0.24, 1.28] |
| 12 Patent ductus arteriosus | 2 | 111 | RR (fixed), 95% CI | 1.39 [0.91, 2.14] |
| 13 Pneumothorax | 1 | 73 | RR (fixed), 95% CI | 0.80 [0.33, 1.92] |
| 14 Necrotising enterocolitis | 1 | 776 | RR (fixed), 95% CI | 0.64 [0.32, 1.27] |
| 15 Sepsis | 1 | 776 | RR (fixed), 95% CI | 1.29 [0.90, 1.83] |
| 16 Change mean BP (%) | 1 | 25 | WMD (fixed), 95% CI | 6.80 [-16.83, 30.43] |
| 17 Change left ventricular output (%) | 1 | 25 | WMD (fixed), 95% CI | 26.60 [-16.68, 69.88] |
| 18 Change cerebral blood flow (%) | 1 | 25 | WMD (fixed), 95% CI | 7.80 [-19.80, 35.40] |
| 02 Colloid (albumin) versus crystalloid (saline) in hypotensive infants | ||||
| 01 Death | 1 | 63 | RR (fixed), 95% CI | 1.36 [0.48, 3.82] |
| 02 Any P/IVH | 1 | 63 | RR (fixed), 95% CI | 1.52 [0.68, 3.42] |
| 03 P/IVH grade 3-4 | 1 | 63 | RR (fixed), 95% CI | 1.61 [0.42, 6.19] |
| 04 Failed treatment | 2 | 165 | RR (fixed), 95% CI | 0.75 [0.53, 1.06] |
| 05 Chronic lung disease | RR (fixed), 95% CI | Subtotals only | ||
| 06 Patent ductus arteriosus | 1 | 63 | RR (fixed), 95% CI | 1.08 [0.72, 1.61] |
| 07 Necrotising enterocolitis | 1 | 63 | RR (fixed), 95% CI | 1.94 [0.38, 9.83] |
| 08 Sepsis | 0 | 0 | RR (fixed), 95% CI | No numeric data |
| 09 Change mean BP (%) | 1 | 102 | WMD (fixed), 95% CI | 9.90 [1.22, 18.58] |
| 03 Albumin versus no treatment in normotensive infants | ||||
| 01 Death | 1 | 25 | RR (fixed), 95% CI | 0.92 [0.23, 3.72] |
| 02 Periventricular leucomalacia in survivors | 0 | 0 | RR (fixed), 95% CI | No numeric data |
| 03 Change mean BP (%) | 1 | 25 | WMD (fixed), 95% CI | 6.80 [-16.83, 30.43] |
| 04 Change left ventricular output (%) | 1 | 25 | WMD (fixed), 95% CI | 26.60 [-16.68, 69.88] |
| 05 Change cerebral blood flow (%) | 1 | 25 | WMD (fixed), 95% CI | 7.80 [-19.80, 35.40] |
| 04 Fresh frozen plasma versus no treatment | ||||
| 01 Death | 3 | 654 | RR (fixed), 95% CI | 1.05 [0.81, 1.36] |
| 02 Any P/IVH | RR (fixed), 95% CI | Subtotals only | ||
| 03 P/IVH grade 2-4 | RR (fixed), 95% CI | Subtotals only | ||
| 04 P/IVH grade 3-4 | 1 | 80 | RR (fixed), 95% CI | 0.55 [0.21, 1.47] |
| 05 Death or P/IVH | RR (fixed), 95% CI | Subtotals only | ||
| 06 Death or P/IVH grade 3-4 | RR (fixed), 95% CI | Subtotals only | ||
| 07 Periventricular leucomalacia in survivors examined | 1 | 282 | RR (fixed), 95% CI | 0.76 [0.40, 1.45] |
| 08 Severe neurodevelopmental disability in survivors | 1 | 408 | RR (fixed), 95% CI | 0.80 [0.48, 1.34] |
| 09 Death or severe neuodevelopmental disability | 1 | 515 | RR (fixed), 95% CI | 0.94 [0.73, 1.22] |
| 10 Cerebral palsy in survivors | 1 | 408 | RR (fixed), 95% CI | 0.79 [0.46, 1.34] |
| 11 Failed treatment (hypotension) in infants born 1990-1991 | 1 | 428 | RR (fixed), 95% CI | 0.71 [0.27, 1.82] |
| 12 Patent ductus arteriosus | 2 | 111 | RR (fixed), 95% CI | 1.39 [0.91, 2.14] |
| 13 Pneumothorax | 1 | 73 | RR (fixed), 95% CI | 0.80 [0.33, 1.92] |
| 14 Necrotising enterocolitis | 1 | 515 | RR (fixed), 95% CI | 0.22 [0.06, 0.74] |
| 15 Sepsis | 1 | 515 | RR (fixed), 95% CI | 1.65 [1.13, 2.40] |
| 05 Gelatin versus no treatment | ||||
| 01 Death | 1 | 519 | RR (fixed), 95% CI | 1.22 [0.86, 1.72] |
| 02 Any P/IVH in survivors examined | 1 | 278 | RR (fixed), 95% CI | 0.89 [0.58, 1.34] |
| 03 P/IVH grade 2-4 in survivors examined | 1 | 278 | RR (fixed), 95% CI | 1.12 [0.56, 2.27] |
| 04 Death or P/IVH in infants examined | 1 | 410 | RR (fixed), 95% CI | 1.01 [0.78, 1.30] |
| 05 Death or P/IVH grade 3-4 in infants examined | 1 | 410 | RR (fixed), 95% CI | 1.23 [0.90, 1.68] |
| 06 Periventricular leucomalacia in survivors examined | 1 | 278 | RR (fixed), 95% CI | 0.62 [0.31, 1.24] |
| 07 Severe neurodevelopmental disability in survivors | 1 | 401 | RR (fixed), 95% CI | 0.79 [0.47, 1.33] |
| 08 Death or severe neuodevelopmental disability | 1 | 519 | RR (fixed), 95% CI | 1.05 [0.82, 1.34] |
| 09 Cerebral palsy in survivors | 1 | 401 | RR (fixed), 95% CI | 0.74 [0.42, 1.28] |
| 10 Failed treatment (hypotension) in infants born 1990-1991 | 1 | 431 | RR (fixed), 95% CI | 0.40 [0.13, 1.25] |
| 11 Necrotising enterocolitis | 1 | 519 | RR (fixed), 95% CI | 1.06 [0.52, 2.15] |
| 12 Sepsis | 1 | 519 | RR (fixed), 95% CI | 0.93 [0.60, 1.44] |
| 06 Gelatin versus fresh frozen plasma | ||||
| 01 Death | 1 | 518 | RR (fixed), 95% CI | 1.17 [0.83, 1.64] |
| 02 Any P/IVH in survivors examined | 1 | 266 | RR (fixed), 95% CI | 0.74 [0.49, 1.10] |
| 03 P/IVH grade 2-4 in survivors examined | 1 | 266 | RR (fixed), 95% CI | 1.20 [0.58, 2.50] |
| 04 Death or P/IVH in infants examined | 1 | 408 | RR (fixed), 95% CI | 0.95 [0.74, 1.21] |
| 05 Death or P/IVH grade 3-4 in infants examined | 1 | 408 | RR (fixed), 95% CI | 1.22 [0.89, 1.67] |
| 06 Periventricular leucomalacia in survivors examined | 1 | 266 | RR (fixed), 95% CI | 0.81 [0.38, 1.72] |
| 07 Severe neurodevelopmental disability in survivors | 1 | 399 | RR (fixed), 95% CI | 0.99 [0.57, 1.72] |
| 08 Death or severe neuodevelopmental disability | 1 | 518 | RR (fixed), 95% CI | 1.11 [0.86, 1.43] |
| 09 Cerebral palsy in survivors | 1 | 399 | RR (fixed), 95% CI | 0.94 [0.52, 1.69] |
| 10 Failed treatment (hypotension) in infants born 1990-1991 | 1 | 429 | RR (fixed), 95% CI | 0.56 [0.17, 1.90] |
| 11 Necrotising enterocolitis | 1 | 518 | RR (fixed), 95% CI | 4.92 [1.44, 16.80] |
| 12 Sepsis | 1 | 518 | RR (fixed), 95% CI | 0.57 [0.39, 0.83] |
| This review is published as a Cochrane review in The
Cochrane Library 2004, Issue 2, 2004 (see www.CochraneLibrary.net for information).
Cochrane reviews are regularly updated as new evidence emerges and in response
to comments and criticisms, and The Cochrane Library should be consulted
for the most recent version of the Review. |
