Mechanical ventilation for newborn infants with respiratory failure due to pulmonary disease

Henderson-Smart DJ, Wilkinson A, Raynes-Greenow CH

Background - Methods - Results - Characteristics of Included Studies - References - Data Tables & Graphs

Cover sheet

Title

Reviewers

Henderson-Smart DJ, Wilkinson A, Raynes-Greenow CH

Dates

Date edited: 25/05/2005
Date of last substantive update: 12/08/2002
Date of last minor update: 25/04/2005
Date next stage expected / /
Protocol first published: Issue 4, 2000
Review first published: Issue 4, 2002

Contact reviewer

Prof David J Henderson-Smart
Director
NSW Centre for Perinatal Health Services Research
Queen Elizabeth II Research Institute
Building DO2
University of Sydney
Sydney
NSW AUSTRALIA
2006
Telephone 1: +61 2 93517318
Telephone 2: +61 2 93517728
Facsimile: +61 2 93517742
E-mail: dhs@perinatal.usyd.edu.au

Contribution of reviewers

All authors had input into the protocol for the review. Henderson-Smart and Raynes-Greenow carried out the search, assessed the studies, extracted and entered the data. Henderson-Smart wrote the text and all authors contributed to editing.

Internal sources of support

Centre for Perinatal Health Services Research, University of Sydney, AUSTRALIA
Royal Prince Alfred Hospital, Sydney, AUSTRALIA
Neonatal Unit, Department of Paediatrics, Oxford University, UK

External sources of support

None

What's new

This updates the existing review "Mechanical ventilation for newborn infants with respiratory failure due to pulmonary disease" originally published in The Cochrane Library, Issue 4 2002 (Henderson-Smart 2002).

No new trials were found. The reviewers' conclusions regarding the need for further trials has been reworded.

Dates

Date review re-formatted: / /
Date new studies sought but none found: 01/04/2005
Date new studies found but not yet included/excluded: / /
Date new studies found and included/excluded: / /
Date reviewers' conclusions section amended: 29/03/2005
Date comment/criticism added: / /
Date response to comment/criticisms added: / /

Text of review

Synopsis

Mechanical ventilation of newborn infants with severe lung disease results in reduced mortality.

Mechanical ventilation with intermittent positive or negative pressure was introduced in the 1960s. It was compared with standard treatment in five trials for infants with very severe lung disease and resulted in a reduction in mortality. This effect was observed principally in infants with birth weights over two kilograms. Mechanical ventilation has become standard therapy for severe respiratory failure. There have been no trials in modern neonatal intensive care units so the magnitude of the benefits and harms in current practice are not known.

Abstract

Background

Before the 1960s newborn infants with severe lung disease, usually due to respiratory distress syndrome (RDS), had a very high mortality rate. Standard treatment consisted of supportive measures including supplemental oxygen and correction of metabolic acidosis. Mechanical ventilation (MV) was introduced in the 1960s to correct hypoxaemia and respiratory acidosis in infants who were likely to die. MV is now standard treatment for infants with severe RDS but the degree to which this made a contribution to the outcome of such infants compared with standard neonatal care, is uncertain.

Objectives

To evaluate the effects of the use of MV compared with no MV on mortality and morbidity in newborn infants with severe respiratory failure due to pulmonary disease.

Search strategy

Searches were last updated in March 2005 on the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2005), MEDLINE from 1966 to March 2005 and EMBASE from 1980 to March 2005. In order to detect trials that may not have been published in full, searches were carried out of the Oxford Database of Perinatal Trials and for abstracts published by the Society for Pediatric Research (1967 to 2004 inclusive) and the European Society for Pediatric Research (1970 to 2004 inclusive). Experts were consulted with emphasis on those who were in active neonatal practice in the 1960s and 1970s when the majority of these trials were likely to have been done.

Selection criteria

Randomised or quasi-randomised controlled trials in newborn infants with respiratory failure due to pulmonary disease evaluating the use of MV versus standard neonatal care without MV.

Data collection & analysis

The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. Two authors independently assessed eligibility, methodological quality of each trial and extracted the data. Additional information was obtained from all trial authors on methodology or data. The data were analysed using relative risk and risk difference and their 95% confidence intervals. A fixed effect model was used for meta-analyses.

Main results

The five eligible trials reported on a total of 359 infants with RDS. In one study there is a higher neonatal mortality in the mechanical ventilation group [7/10 vs 1/10; RR 7.00 (1.04, 46.95)]. Overall the risk of any reported mortality is less frequent in the mechanical ventilation group with the upper 95% confidence limit on 1.00 [summary RR 0.86 (0.74, 1.00), RD -0.10 (-0.20, -0.01), NNT 10 (5, 100)]. In infants with a birth weight of 1 - 2 kg, no significant difference in mortality is found [summary RR for two trials 0.86 (0.70, 1.07)]. In infants with a birth weight of more than 2 kg, one study reports a significant reduction in mortality in the MV group compared with control [RR 0.67 (0.51, 0.86)]; overall for this birth weight group there is a significant reduction in mortality with MV in the two trials [summary RR 0.67 (0.52, 0.87), RD -0.27 (-0.45, -0.10), NNT 4 (2, 10)].

Any IVH at autopsy is not significantly different between the groups in any study or overall in four studies reporting on 202 infants who had an autopsy. Pneumothorax was reported in two studies of 275 infants and there is a non-significant trend towards an increase in the mechanical ventilation group [summary RR 2.75 (0.72, 10.45)].

Reviewers' conclusions

When MV was introduced in the 1960s to treat infants with severe respiratory failure due to pulmonary disease, trials showed an overall reduction in mortality which was most marked in infants born with a birthweight of more than 2 kg. This review does not provide information to evaluate the relative benefits or harms of MV in the setting of modern perinatal care. Introduction of mechanical ventilation into new settings, such as those without full intensive care support, should ideally be evaluated in clinical trials.

Background

Before the 1960s newborn infants with severe lung disease, usually due to respiratory distress syndrome (RDS), had a very high mortality rate (Sinclair 1966). Standard treatment consisted of supportive measures including supplemental oxygen and correction of metabolic acidosis. Mechanical ventilation (MV) was introduced in the 1960s to correct hypoxemia and respiratory acidosis in infants who were likely to die. MV can be administered as either intermittent positive pressure ventilation (IPPV) or as intermittent negative pressure ventilation (INPV). The former requires intubation of the trachea either by the mouth or the nose for a number of days. This can be associated with upper airway trauma, increased pulmonary secretions or infection. INPV requires the infant to be nursed in a negative pressure chamber with a seal around the neck and this could be associated with trauma to that region. Artificial lung inflation could be associated with physical trauma to the lung leading to acute complications such as pneumothorax or chronic complications such as bronchopulmonary dysplasia. Differences in cardio-respiratory stability with or without MV support could be associated with neurological injury indicated by short term markers such as intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL) or in adverse long term neurodevelopmental outcome. Both benefits and harms could be different in infants born at lower gestational ages and birth weights.

The introduction of neonatal intensive care, including MV, during the 1960s and its widespread application in the 1970s was associated with increased survival of very low birthweight infants and was shown to be more cost effective in infants of 1 - 1.5 kg birthweight compared with infants of less than 1 kg (Boyle 1983). Although MV, usually using IPPV, is now a standard treatment (Greenough 1996; Wiswell 2001) it is not clear what the balance of benefits and harms was at the time it was introduced and how these should be interpreted in terms of modern neonatal intensive care. In earlier debates Reynolds 1970 suggested that infants with severe RDS could be managed just as well with excellent standard care, without use of MV. Given the cost of IPPV, the question still arises as to whether it should be introduced as part of neonatal care in resource poor settings, such as in many developing countries (Ho 1996).

The effects of MV have been reviewed previously (Bancalari 1992) but such effects require formal re-examination by repeating the search for randomised controlled trials, including those that may have appeared only in abstract form, to clarify any remaining research questions and to better describe the population of infants who entered these trials.

Objectives

To evaluate the effects of the use of MV compared with no MV on mortality and morbidity in newborn infants with severe respiratory failure due to pulmonary disease.

Pre-specified sub-group analyses were to be carried out according to:
1. RDS as cause of respiratory failure vs all other causes
2. Early vs late (rescue) treatment with MV
3. Type of MV - either IPPV or INPV
4. Gestation (cut-offs at about 28 and 32 weeks)
5. Birth weight (cut-offs at about 1000 and 1500 grams)

Although no trials comparing MV with head box oxygen are likely to have been conducted since the availability of artificial surfactant or the use of positive end-expiratory pressure, if trials utilizing these latter interventions were found, sub-group analyses were to be done according to the use, or not, of these therapies.

Criteria for considering studies for this review

Types of studies

Randomised or quasi-randomised controlled trials

Types of participants

Newborn infants with respiratory failure due to pulmonary disease. Although the original protocol for this review confined the population to preterm infants, the review has been done without that limitation (all newborn infants were eligible) since no upper limit of gestational age was specified in any study.

Types of interventions

MV (IPPV or INPV) versus no MV. Use of rescue MV in controls was allowed.
Not eligible for this review were trials comparing different types of MV (IPPV vs INPV), ventilator techniques (inspiratory times, pressure vs volume cycled or high frequency) or trials in which MV was compared with continuous distending pressure.

Types of outcome measures

Mortality
- first week
- 28 days
- hospital discharge

Morbidity
- pneumothorax
- IVH (all grades and severe grades 3 or 4)
- chronic lung disease (ventilatory support or oxygen at 28 days or at 36 weeks)
- proven systemic infection (positive culture blood, urine, cerebrospinal fluid or other normally sterile body fluid)
- necrotising enterocolitis
- retinopathy of prematurity
- neurodevelopmental abnormalities in childhood (developmental delay, cerebral palsy)

Search strategy for identification of studies

Searches were last updated in March 2005 on the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2005), MEDLINE from 1966 to March 2005 and EMBASE from 1980 to March 2005, using MeSH terms mechanical ventilation, infant newborn, respiratory distress syndrome. In order to detect trials that may not have been published in full, searches were carried out of the Oxford Database of Perinatal Trials and for abstracts published by the Society for Pediatric Research (1967 to 2004 inclusive) and the European Society for Pediatric Research (1970 to 2004). Experts were consulted with emphasis on those who were in active neonatal practice in the 1960s and 1970s when the majority of these trials were likely to have been done.

Methods of the review

The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. The methodological quality of each trial was reviewed independently by two authors for blinding of randomisation, blinding of outcome measurements, and completeness of follow up. Additional information was obtained from all trial authors on methodology or data.

Two authors independently assessed eligibility of retrieved reports, and extracted data; the results were compared and any differences resolved by discussion and consensus.

The data were synthesised using the standard method of the Neonatal Review Group with use of relative risk and risk difference and their 95% confidence intervals. A fixed effect model was used for meta-analyses.

Description of studies

Five published trials (Reid 1967, Silverman 1967, Sinclair 1968, Llewellyn 1970, Murdock 1970) were found and included. All trials were carried out in the latter half of the 1960s. No unpublished trials or trials published only in abstract form were found.

Participants
All studies enrolled infants of more than one kilogram birth weight with respiratory distress. In all but one study, the infants all had clinical and radiological RDS. In the other study (Sinclair 1968) 50% had RDS. No gestational age limits were used and only one study (Sinclair 1968) specified an upper limit for birth weight, at 2.5 kg. The severity of respiratory failure based on oxygen requirements varied. From least to most severe, it was oxygen saturation less than 80% in air (Silverman 1967), use of 40-100% oxygen (Reid 1967), PaO2 75 mm Hg or less in 50% oxygen (Sinclair 1968), PaO2 less than 100 mm Hg in more than 95% oxygen (Llewellyn 1970) and PaO2 less than 50 in 95% or more oxygen (Murdock 1970).

Interventions
Mechanical ventilation was provided in a wide variety of ways. Silverman 1967 and Sinclair 1968 used negative pressure Airsheilds ventilators, Reid 1967 used IPPV via a naso-tracheal tube and Murdock 1970 gave IPPV via a face-mask. Llewellyn 1970 had one group on INPV, one on IPPV with a pressure cycled ventilator and another on IPPV with a volume cycled ventilator. The authors found no statistical difference in outcomes between these different methods and so combined them in the publication. The original data on outcomes for each type of MV is no longer available for analysis (Swyer personal communication).

Outcomes
Mortality was reported in all studies but the period of follow up (during the study period, neonatal or prior to discharge) was variable. Sinclair 1968 reported deaths during the seven day study and in the neonatal period. Silverman 1967 only reported deaths during the seven day study period. Published reports of three trials did not indicate when the deaths had occurred. Dr Paul Swyer, co-author of two of these trials (Murdock 1970, Llewellyn 1970) was contacted and he recalled that deaths were ascertained by hospital discharge. Dr David Reid (Reid 1967) provided time of death information from his trial indicating that all deaths occurred in the first seven days and that there were no late deaths before discharge. The outcome 'any reported mortality' in this review presents data over the longest period follow-up period in each study. All trials reported IVH, but this was only reported for those with autopsies as ultrasound examination was not available in the 1960s. Overall, autopsies were carried out in 79% of the mechanical ventilation group deaths and 91% of the control group deaths.

Methodological quality of included studies

All trials randomly allocated subjects to treatment or control groups and all five concealed the random allocation from clinicians caring for the infants. Neither the treatments nor the outcome assessments were blinded in any trials. Outcomes were ascertained in almost all subjects randomised in each trial.

Results

The five eligible trials reported on a total of 359 infants with RDS.

Mortality
All trials reported mortality. Sinclair 1968 found a higher neonatal mortality in the mechanical ventilation group [7/10 vs 1/10; RR 7.00 (1.04, 46.95)]. Overall in the five trials any reported mortality was less frequent in the mechanical ventilation group with the upper 95% confidence limit of RR on 1.00 [summary RR 0.86 (0.74, 1.00), RD -0.10 (-0.20, -0.01), NNT 10 (5, 100)]. For RR there is a non-significant trend suggesting heterogeneity; for RD there is highly significant heterogeneity.

Two studies reported mortality by birth weight (Reid 1967, Murdock 1970). In infants with a birthweight of 1 - 2 kg no significant difference in mortality was found [summary RR 0.86 (0.70, 1.07)]. In infants with a birth weight of more than 2 kg, one study (Murdock 1970) reported a significant reduction in mortality in the MV group compared with control [RR 0.67 (0.51, 0.86)] and, overall, in the two trials there was a significant reduction in mortality with MV [summary RR 0.67 (0.52, 0.87), RD -0.27 (-0.45, -0.10), NNT 4 (2, 10)].

Intraventricular haemorrhage (IVH)
Any IVH at autopsy was not significantly different between the groups in any study or overall in four studies reporting on 202 infants who had an autopsy [summary RR 1.05 (0.79, 1.39)].

Pneumothorax
Pneumothorax was reported in two studies (Silverman 1967, Llewellyn 1970) of 275 infants and there was a non-significant trend towards an increase in the mechanical ventilation group [summary RR 2.75 (0.72, 10.45)].

Proven systemic infection was only reported in one trial (Murdock 1970) which found five cases of septicaemia in the ventilated group (45 survivors and 96 with postmortem examination) and none in the control group (eight survivors and 45 with postmortem examination).

Other prespecified outcomes could not be assessed.

Subgroup analysis by IPPV and INPV was not done because in the largest study (Llewellyn 1970) outcomes by these modalities were not available. Subgroup analyses by gestation, cause of respiratory distress, and early or late use of intervention could not be carried out.

Discussion

The trials included in this review were carried out in the 1960s when neonatal intensive care was just being introduced and overall care was less sophisticated than current neonatal care. The equipment and methods used to apply mechanical ventilation cannot be compared to those used now (reviewed by Wiswell 2001). Intermittent negative pressure is now rarely used and ventilators for IPPV have been especially developed for use with newborn infants (Wiswell 2001). Mortality rates for infants with moderate or severe RDS, such as those entered in the studies in this review, were much higher (overall 67%) than observed in the 1980s (5%) (Greenough 1985). This is despite the relatively high birth weight of the infants in the included studies compared to current NICU infants. Furthermore, treatments such as antenatal corticosteroids and artificial surfactants were not available. For these reasons there are considerable limitations in applying the results of this review to current NICU practice.

When these trials were done the main question was whether mechanical ventilation could save the lives of infants with severe RDS. Apart from one of the trials, the results suggest that mortality is reduced. Prespecified subgroup analyses could not be carried out to explore the heterogeneity in the overall mortality analysis. Post-hoc examination showed that the trial with a higher mortality in the MV group (Sinclair 1968) had a much lower control group mortality rate (10%) than the other four trials (range 63 - 85%). Caution is also warranted in interpreting the results for 'any mortality' presented here because the outcome was ascertained over different time periods in some studies. As ultrasound and computerised tomographic imaging were not available when these studies were carried out, IVH was ascertained at autopsy and the incidence in survivors is not known.

In some settings, such as some developing countries where resources limit the ability to provide neonatal intensive care, the question of whether MV is worthwhile is still valid (Ho 1996). In such settings it is uncertain what additional benefits MV might provide over oxygen administration alone or other lower cost support such as continuous positive airways pressure (reviewed by Ho 2005a; Ho 2005b).

The results here and those examining the cost effectiveness of neonatal intensive care (Boyle 1983) suggest the infants of greater birthweight might benefit more in settings where MV is being introduced. Furthermore, more MV resources are used in treating the lowest birth weight infants (Doyle 1996).

Reviewers' conclusions

Implications for practice

Implications for research

It is unlikely that further trials comparing MV with headbox oxygen only for neonates with severe pulmonary failure would be carried out in a modern perinatal care setting. Current research questions now focus on comparing different types of MV or comparing MV with other means of support such as CPAP. Introduction of mechanical ventilation into new settings, such as those without full intensive care support, should ideally be evaluated in clinical trials.

Acknowledgements

Drs William Silverman, John Sinclair, Paul Swyer and David Reid kindly provided additional information about their trials. Dr Jackie Ho from Malaysia commented on the review from a developing country perspective.

Potential conflict of interest

None

Characteristics of included studies

Study	Methods	Participants	Interventions	Outcomes	Notes	Allocation concealment
Llewellyn 1970	Concealment of randomisation - yes; blinding of intervention - no; completeness of follow up - yes; blinding of outcome assessment - no	44 infants of 127 admitted with RDS; PaO2 < 100 in > 95%	IPPV via face mask using pressure (Bird Mk VIII) or volume (Bourns Pediatric Respirator, model LS 104) cycled ventilator, maximum pressure of 20 cms H2O vs Standard treatment (servocontrolled ventilator, 4 - 6 hrly blood gases, PaO2 kept at 50 - 80, metabolic acidosis corrected with NaHCO3, 10% dextrose)	Mortality before discharge, intubation for IPPV, duration of oxygen therapy	All infants outborn May 1968 - March 1969. Dr Swyer provided additional information that randomisation was concealed, standard errors reported, deaths were before discharge.	A
Murdock 1970	Concealment of randomisation - yes; blinding of intervention - no; completeness of follow up - yes; blinding of outcome assessment - no	221 with RDS with PaO2 < 50 mmHg in FiO2 > 0.95 or cyanosis despite such FiO2 and blood gas not available or apnea unresponsive to bag and mask ventilation	Mechanical ventilation (IPPV with pressure or volume cycled ventilators and endotracheal tubes, INPV preferably without intubation) vs standard care (FiO2 to keep PaO2 60 - 100 mmHg, 10% dextrose, servocontrolled incubator, NaHCO3 to keep pH > 7.25)	Mortality before discharge by birthweight, Pneumothorax, IVH at autopsy	All infants outborn November 1965 - February 1968. Dr Swyer provided additional information that randomisation was concealed, standard errors were reported and deaths were before discharge.	A
Reid 1967	Concealment of randomisation - yes (off-site by independant statistician); blinding of intervention - no; completeness of follow up - unclear; blinding of outcome assessment - no	20 infants with clinical RDS, Silverman Score > 4, in 40 - 100% O2 and an initial capillary pH of < 7.20 Infants of < 1000gms birthweight excluded	IPPV vs standard treatment (10% dextrose plus NaHCO3, oxygen to prevent cyanosis, heated humidified incubators)	Mortality by birthweight, IVH at autopsy (autopsy rate 100%)	All infants given Ampicillin and Cloxacillin 1964 - 66. Dr Reid supplied additional information about the method of randomisation and details of the deaths.	A
Silverman 1967	Concealment of randomisation - yes, paired by outborn (18) and inborn (36) and in 500gm weight groups; blinding of intervention - no; completeness of follow up - yes; blinding of outcome assessment - no	474 admissions, 420 did not meet criteria, 54 infants included at mean age of 8 hrs with clinical and radiological (independent assessment) diagnosis of RDS and cyanosis or capillary SaO2 < 80% in air or PCO2 > 50 mmHg and birthweight > 1kg	INPV in Airshields incubator, pressures -15 to -45 cms H2O vs standard care (dextrose and NaCO3 IV)	Mortality during the 7 day study period, IVH at autopsy, pneumothorax	February 1963 - December 1964 Author confirmed that developmental follow up not done	A
Sinclair 1968	Concealment of randomisation - yes; blinding of intervention - no; completeness of follow up - yes; blinding of outcome assessment - no	20 infants (50% with RDS) with birthweight 1000 - 2500gms, < 24 hrs old, pH < 7.25 or PaO2 < 76 in FiO2 0.5	Randomised to 4 groups according to use of unlimited O2, rapid bicarbonate administration and assisted ventilation with INPV (Airshields) In this review, the 2 groups which received INPV were compared with the 2 groups not receiving INPV.	Mortality (first week and neonatal), IVH at autopsy (any or massive)	April 1966 - January 1967 Author confirmed that developmental follow up not done	A

References to studies

References to included studies

Llewellyn 1970 {published and unpublished data}

Llewellyn MA, Tilak KS, Swyer PR. A controlled trial of assisted ventilation using an oro-nasal mask. Archives of Disease in Childhood 1970;45:453-9.

Murdock 1970 {published and unpublished data}

Murdock AI, Linsao L, Reid MMcM, Sutton MD, Tilak KS, Ulan OA, Swyer PR. Mechanical ventilation in the respiratory distress syndrome: a controlled trial. Archives of Disease in Childhood 1970;45:624-33.

Reid 1967 {published data only}

* Reid DHS, Tunstall ME, Mitchell RG. A controlled trial of artificial respiration in the respiratory-distress syndrome of the newborn. Lancet 1967;1:532-3.

Reid DHS. Perinatal repiratory problems with special emphasis on the treatment of respiratory failure in the newborn with intermittent positive-pressure respiration. MD Thesis, University of St Andrews (now held in University of Dundee), Scotland 1968.

Silverman 1967 {published and unpublished data}

Silverman WA, Sinclair JC, Gandy GM, Finster M, Bauman WA, Agate FJ. A controlled trial of management of respiratory distress syndrome in a body-enclosing respirator. 1. Evaluation of safety. Pediatrics 1967;39:740-8.

Sinclair 1968 {published and unpublished data}

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.

* indicates the primary reference for the study

Other references

Additional references

Bancalari 1992

Bancalari E, Sinclair JC. Mechanical ventilation. In: Sinclair JC, Bracken MB, editor(s). Effective Care of the Newborn Infant. Oxford: Oxford University Press, 1992:200-20.

Boyle 1983

Boyle MH, Torrance GW, Sinclair JC, Horwood MD. Economic evaluation of neonatal intensive care of very-low-birth-weight infants. New England Journal of Medicine 1983;308:1330-7.

Doyle 1996

Doyle LW, Davis P, Dharmalingham A, Bowman E. Assisted ventilation and survival of extremely low birthweight infants. Journal of Paediatrics and Child Health 1996;32:138-42.

Greenough 1985

Greenough A, Roberton NRC. Morbidity and survival in neonates ventilated for the respiratory distress syndrome. British Medical Journal 1985;290:597-600.

Greenough 1996

Greenough A, Roberton NRC. Respiratory distress syndrome. In: Greenough A, Milner AD, Roberton NRC, editor(s). Neonatal Respiratory Disorders. London: Arnold, 1996:238-79.

Ho 1996

Ho NK. Priorities in neonatal care in developing countries. Singapore Medical Journal 1996;37:424-7.

Ho 2005a

Ho JJ, Subramaniam P, Henderson-Smart DJ, Davis PG. Continuous distending pressure for the respiratory distress syndrome in preterm infants. In: The Cochrane Database of Systematic Reviews, Issue 1, 2005.

Ho 2005b

Ho JJ, Henderson-Smart DJ, Davis PG. Early versus delayed initiation of continuous distending pressure for respiratory distress syndrome in preterm infants. In: The Cochrane Database of Systematic Reviews, Issue 1, 2005.

Reynolds 1970

Reynolds REO. Indications for mechanical ventilation in infants with hyaline membrane disease. Pediatrics 1970;46:193-202.

Sinclair 1966

Sinclair JC. Prevention and treatment of the respiratory distress syndrome. Pediatric Clinics of North America 1966;13:711-30.

Wiswell 2001

Wiswell TE, Donn SM (eds). Mechanical ventilation and exogenous surfactant update. Clinics in Perinatology 2001;28.

Other published versions of this review

Henderson-Smart 2002

Henderson-Smart DJ, Wilkinson A, Raynes-Greenow CH. Mechanical ventilation for newborn infants with respiratory failure due to pulmonary disease. In: The Cochrane Database of Systematic Reviews, Issue 4, 2002.

Comparisons and data

01 Mechanical ventilation vs control
01.01 Any reported mortality
01.02 Mortality 1 - 2 kg
01.03 Mortality more than 2 kg
01.04 Any IVH in infants with an autopsy
01.05 Pneumothorax

Comparison or outcome	Studies	Participants	Statistical method	Effect size
01 Mechanical ventilation vs control
01 Any reported mortality	5	359	RR (fixed), 95% CI	0.86 [0.74, 1.00]
02 Mortality 1 - 2 kg	2	140	RR (fixed), 95% CI	0.86 [0.70, 1.07]
03 Mortality more than 2 kg	2	101	RR (fixed), 95% CI	0.67 [0.52, 0.87]
04 Any IVH in infants with an autopsy	5	202	RR (fixed), 95% CI	1.05 [0.79, 1.39]
05 Pneumothorax	2	275	RR (fixed), 95% CI	2.75 [0.72, 10.45]

Notes

Published notes

Amended sections

Cover sheet
Synopsis
Abstract
Background
Search strategy for identification of studies
Discussion
Reviewers' conclusions
References to studies
Other references
Characteristics of included studies

Contact details for co-reviewers

Ms Camille Raynes-Greenow
Research Officer
Centre for Perinatal Health Services Research
University of Sydney
Queen Elizabeth Institute
University of Sydney
Sydney
NSW AUSTRALIA
2006
Telephone 1: +61 2 9351 7740
Facsimile: +61 2 9351 7742
E-mail: camillerg@perinatal.usyd.edu.au
Secondary address:
Telephone: +61 2 9351 7740
Facsimile: +61 2 9351 7742

Dr Andrew Wilkinson
Head
Neonatal Medicine
John Radcliffe Hospital
Headington
Oxford
UK
OX3 9DU
E-mail: andrew.wilkinson@paediatrics.oxford.ac.uk

The review is published as a Cochrane review in The Cochrane Library, Issue 3, 2005 (see http://www.thecochranelibrary.com 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.