The search revealed one new published eligible trial Sandri (2004). Author clarification regarding randomization and outcome definitions has been received for one trial (Han 1987) and added to the review. The completed trial by Thomson has not been published except in abstract form and is in the 'Trials awaiting assessment' section.
Not enough evidence to show the effect of continuous positive airways pressure (CPAP) applied through the nose to prevent respiratory problems in preterm babies
Preterm babies (born before 37 weeks) may need help to breathe properly. These babies can be helped to breathe mechanically by intermittent airflow via a tube placed in their windpipe (Intermittent Positive Pressure Ventilation, IPPV) but this is invasive and may be associated with complications. They can also be given continuous pressure in their airways by controlling the pressure of the gas entering the nose. The review did not find enough evidence from trials to show the effect of using prophylactic nasal CPAP to prevent respiratory problems requiring IPPV. More research is needed.
Cohort studies (Avery 1987; Jonsson 1997) have suggested that early post-natal nasal continuous positive airways pressure (CPAP) may be beneficial in reducing the need for intubation and intermittent positive pressure ventilation, and in preventing chronic lung disease in preterm or low birth weight infants.
To determine if prophylactic nasal CPAP commenced soon after birth regardless of respiratory status in the very preterm or very low birth weight infant reduces the use of IPPV and the incidence of chronic lung disease (CLD) without adverse effects.
The search was updated in April 2005. The standard search strategy of the Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal Trials, Cochrane Library Issue 1 2005, MEDLINE 1966-April 2005, previous reviews including cross references, abstracts, conferences, symposia, proceedings, expert informants, journal hand searching mainly in the English language.
All trials using random or quasi-random patient allocation of very preterm infants < 32 weeks gestation and / or < 1500 gms at birth were eligible. Comparison had to be between prophylactic nasal CPAP commencing soon after birth regardless of the respiratory status of the infant compared with "standard" methods of treatment where CPAP or IPPV is used for a defined respiratory condition.
Standard methods of the Cochrane Collaboration and its Neonatal Review Group, including independent assessment of trial quality and extraction of data by each author, were used. Data were analysed using relative risk (RR). Meta-analysis was performed using a fixed effects model.
There are no statistically significant differences in any of the outcomes studied in either of the eligible trials (Han 1987; Sandri 2004) reporting on 82 and 230 infants respectively. In Han 1987 there are trends towards increases in the incidence of BPD at 28 days [RR 2.27 (0.77, 6.65)], death [RR 3.63 (0.42, 31.08)] and any IVH [RR 2.18 (0.84, 5.62)] in the CPAP group. In Sandri 2004 there is a trend towards an increase in IVH grade 3 or 4 [RR 3.0 (0.96, 28.42)] in the CPAP group. No outcome was significantly different in any of the meta-analyses.
There is currently insufficient information to evaluate the effectiveness of prophylactic nasal CPAP in very preterm infants. Neither of the included studies reviewed showed evidence of benefit in reducing the use of IPPV. The tendency for some adverse outcomes to be increased is of concern and further multicentre randomized controlled trials are needed to clarify this.
Cohort studies of variations in practice between centres (Avery 1987; Jonsson 1997) have suggested that early nasal continuous positive airway pressure (CPAP) may be beneficial in reducing the need for intubation for intermittent positive pressure ventilation (IPPV) and the incidence of chronic lung disease (CLD).
Cohort studies using historical controls (Jacobsen 1993; Gittermann 1997) have suggested that prophylactic nasal CPAP in very low birth weight (VLBW) infants is effective in reducing the need for IPPV without worsening other measures of neonatal outcome. In these studies no significant decrease in the incidence of CLD was found with elective CPAP.
There are several problems interpreting these observational studies. Comparisons between centres and between infants in different eras are confounded by variations in the characteristics of infants entering treatment programs, such as the gestational age of cohorts based on birth weight (Avery 1987) and in cointerventions such as antenatal steroid administration (Gittermann 1997). Furthermore, the major end-point (intubation for IPPV) is often a clinical decision and the general approach towards intubation is often more 'restrictive' in centres which use the policy of elective CPAP as part of a package of minimal intervention and 'permissive hypercarbia'.
Randomized controlled trials are required to minimise bias and give a more precise measure of the effectiveness of prophylactic nasal CPAP (Lundstrom 1996). Bancalari 1992 carried out an earlier systematic review of this subject.
To determine if prophylactic nasal CPAP commenced soon after birth regardless
of respiratory status in the very preterm or very low birth weight infant
reduces the use of IPPV and the incidence of chronic lung disease without
adverse effects.
Subgroup analysis was planned to address the following hypotheses;
1) Infants born at the lowest gestational ages (e.g. < 28 weeks or
with a birth weight < 1000 gms) are less likely to respond in terms of
avoiding IPPV.
2) Use of CPAP at pressures of 5 cms H2O or more will be more effective than administration at lower pressures.
3) Use of CPAP via the nose rather than via intubation of the pharynx or trachea will be more effective.
All trials using random or quasi-random patient allocation were eligible.
Very preterm infants < 32 weeks gestation and / or < 1500 gms at birth.
Prophylactic nasal CPAP commencing soon after birth regardless of the respiratory status of the infant compared with "standard" methods of treatment where CPAP, and/or IPPV, are used for a defined respiratory condition. Trials in which nasal CPAP was used early in the treatment of the respiratory distress syndrome were not eligible for this review and this is considered in other reviews (Ho 2004a, Ho 2004b).
The main measures of the response to treatment sought in this review were a reduction in the use of IPPV and in the incidence of chronic lung disease.
Outcomes nominated a priori
1) Failure of treatment as indicated by recurrent apnea, hypoxia, hypercarbia (PaCO2 > 60) and increasing FiO2 requirements
2) Use of IPPV
3) Mortality at any time
4) Rate of chronic lung disease (or bronchopulmonary dysplasia); a) oxygen
therapy at 28 days with or without an abnormal chest xray; b) oxygen therapy
at 36 weeks postmenstrual age
5) Pulmonary air leaks (pneumothorax, pneumomediastinum)
6) Side effects (nasal injury, feed intolerance, subglottic stenosis, laryngeal injury)
7) Rate of intraventricular hemorrhage and periventricular leukomalacia
8) Necrotizing enterocolitis (proven by radiology or at surgery)
9) Rate of systemic infection (proven or suspected)
10) Retinopathy of prematurity
11) Use of health care resources/costs of care
12) Neurodevelopmental status at follow up
The standard search strategy of the Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal Trials, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2005), MEDLINE (text search for 'CPAP' or 'continuous positive airway pressure' or 'continuous distending pressure' and MeSH heading 'infant, premature') 1966 to April 2005, previous reviews including cross references, abstracts, conference or symposia proceedings, expert informants, journal hand searching mainly in the English language. Abstracts of the American Society for Pediatric Research were hand searched from 1996 to 2004 inclusive.
Standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. The methodological quality of each trial was independently reviewed by the second and third authors.
Each author extracted the data separately, then the data were compared and differences resolved. The standard methods of the Neonatal Review Group were used to synthesise data using relative risk (RR) and meta-analysis was performed using a fixed effects model.
Participants
Full details of the two included studies (Han 1987; Sandri 2004) are given in the Table of Included Studies. Han 1987
reported on 82 infants less than 33 weeks gestational age (GA) randomized
(stratified by sex) in the first two hours after birth to prophylactic nasal
CPAP (n = 43) or control (head box oxygen as required, n = 39). The mean
GAs were 29.4 and 30 weeks and mean birthweights 1290 and 1400 gms, respectively.
Sandri 2004 reported on 230 infants of 28 -
31 weeks GA randomized within 30 minutes of birth to nasal CPAP (n = 115)
or control (n = 115). The mean GAs were 30 and 29.9 weeks and mean birthweights
1370 and 1339 gms, respectively.
In the Han 1987 study no information was
given as to the numbers of infants who were eligible but not randomized.
No mother received antenatal corticosteroids and postnatal surfactant therapy
was not available. In the Sandri 2004 study
193 eligible infants were not randomized as there was either insufficient
time to obtain consent or the attending neonatologist was not compliant with
the study protocol. Prenatal corticosteroids steroids were given to the mothers
of 83.3% infants in the CPAP group and 82.4% of the infants in the control
group. Postnatal surfactant was given to 22.6% infants in the CPAP group
and 21.7% in the control group.
Intervention
In Han 1987 the optimal level of CPAP was determined
by measuring pressure in the lower esophagus and using the CPAP that resulted
in a small increase in the former (Tanswell 1980).
Thirty three percent of the control infants also received CPAP and 11 of
these 13 infants received it by six hours of age. In Sandri 2004
six centimetres of nasal CPAP was used. In the control group 66 infants
(57.4%) received CPAP after 30 minutes (at a median age of 108.5 minutes).
Outcomes
A number of outcomes were not defined by the authors in the first published paper (Han 1987) but have been clarified by contact with Dr Han (see table of included studies). The outcomes defined in Sandri 2004 included neonatal
death, IVH of greater than grade 2, PVL, ROP greater than grade 2, NEC, sepsis,
CLD (oxygen at 36 weeks postmenstrual age), air leaks and PDA.
Other completed or ongoing studies
One United Kingdom multicentre trial (Thomson 2002) has been completed but not yet published and awaits assessment. Another Australian multicentre trial (Morley 2001) is ongoing.
Details are given in the Table of Included Studies. In the Han 1987 trial randomization was concealed but treatment was not blinded. Five infants (10%) were excluded after randomization (two treatment, three control). There was blinding of the assessment of radiological outcomes for RDS and BPD. The trial stopped early because of concern from the planned interim analysis after entry of every 30 infants that the outcomes in the treatment group were possibly worse. In the Sandri 2004 trial randomization was concealed by use of a central telephone service and stratified by weeks of gestational age in blocks of six. The treatment was not blinded and it was not stated whether there was blinding of any of the outcomes. Follow-up was complete.
Use of IPPV (Outcome table 01)
Both eligible trials reported on this outcome. There is no significant
difference in the use of IPPV between CPAP and control groups in either trial
or on meta-analysis [312 infants, typical RR 1.13 (0.72, 1.79)]
Chronic lung disease (02, 03)
Han 1987 reported no statistically significant
difference between CPAP and control groups in the incidence of BPD at 28
days [82 infants, RR 2.27 (0.77, 6.65)]. Sandri 2004
reported no significant difference in the outcome of chronic lung disease
at 36 weeks between CPAP and control groups [230 infants, RR 2.00 (0.18,
21.75)].
Pneumothorax (04)
Both studies reported the rates of pnemothorax. There are no significant
differences in the rates between CPAP and control groups in either study
or in the meta-analysis [312 infants, typical RR 0.95 (0.34, 2.60)].
Mortality (05)
Neonatal mortality was reported for a total of 312 infants in the two studies. In Han 1987
there is a non-significant trend towards an increase in mortality in the
CPAP group [RR 3.63 (0.42, 31.08)]. Overall in the two studies there is no
significant difference in mortality between the CPAP and control groups [312
infants, typical RR 1.29 (0.45, 3.67)]
Intraventricular hemorrhage (IVH) (06, 07)
Han 1987 reported a trend towards an increase in IVH of any grade [RR 2.18 (0.84, 5.62)] in the CPAP group. Sandri 2004 reported more severe grades 3 or 4 IVH and found a trend towards an increase in the CPAP group [RR 3.0 (0.96, 28.42)].
Periventricular leukomalacia (PVL) ((08)
PVL was only reported by Sandri 2004 who found no significant difference between the CPAP and control groups [RR 0.33 (0.04, 3.16)]
Necrotizing enterocolitis (NEC) (09)
Han 1987 reported a trend towards a reduction
in the incidence of NEC in the CPAP group. There was no significant difference
in the two studies overall [312 infants, typical RR 0.56 (0.22, 1.44)].
Retinopathy of prematurity (ROP) (10)
Rates of ROP grades 3 or 4 were reported in both studies. There are no
significant differences in the rates between the CPAP and control groups
in either study or in the meta-analysis [312 infants, typical RR 0.67. (0.13,
3.32)].
Sepsis (11)
Rates of sepsis were reported in both studies. There are no significant
differences in the rates between the CPAP and control groups in either study
or in the meta-analysis [312 infants, typical RR 1.01, 0.61, 1.67)].
Subglottic stenosis (12)
Subglottic stenosis was only reported by Han 1987 in 82 infants. No significant difference in rates were found between CPAP and control groups [RR 0.30 (0.01, 7.23)].
Use of surfactant (13)
This outcome was added post hoc. Sandri 2004
reported the use of surfactant in the control and treatment groups and found
no statistical significance [RR 1.04 (0.64, 1.69)].
Failure of treatment as indicated by recurrent apnea, hypoxia, hypercarbia (PaCO2 > 60) and increasing FiO2 requirements, the use of health care resources, and the neurodevelopmental status of the infants at follow up were not reported in either study. The subgroup analyses nominated a priori could not be carried out.
The results of this review should be interpreted with caution because of the small number of subjects studied.
Based on the results of the two included studies, there is no evidence to suggest that elective nasal CPAP reduces the need for IPPV compared with standard methods of treatment. This finding contrasts with those obtained from observational studies (Avery 1987; Jacobsen 1993; Jonsson 1997; Gittermann 1997) that did not use randomization and were therefore subject to bias in the selection of controls. Furthermore, avoidance of intubation and IPPV was part of the 'treatment package' of minimal intervention used in these studies. Failure to find a reduction in CLD and neonatal death is consistent with observational studies (Jacobsen 1993; Jonsson 1997; Gittermann 1997).
The use of CPAP in 33% of the control infants (80% of these by six hours of age) in Han's study and 57.4% of the control infants in Sandri's study could have reduced the chance of finding a difference between the experimental and control groups.
The Han 1987 trial was stopped early and therefore did not have adequate power to examine the significance of some trends towards increased adverse outcomes. There is some doubt about the generalizability of the results of Han 1987 to current perinatal practice. Antenatal corticosteroids were not used and surfactant therapy was not available, which would have a large impact on neonatal respiratory function and mortality.
A completed randomized trial, conducted in the United Kingdom, entered preterm infants born at 27 - 29 weeks gestation and tested the role of early CPAP, with and without prophylactic surfactant (see studies awaiting assessment, Thomson 2002). The results have been presented only in abstract form.
One ongoing study is examining the effects of nasal CPAP from birth versus intubation in spontaneously breathing infants born at 25-28 weeks gestational age (Morley 2001).
In a previous systematic review (Bancalari 1992) the trial by Drew 1982 was included. Exclusion of the Drew 1982 trial here was because the intervention included intubation at birth followed by CPAP via the endotracheal tube, rather than prophylactic nasal CPAP.
There is insufficient evidence to evaluate the benefits or harms of prophylactic nasal CPAP in very preterm infants.
Both these studies reviewed did not suggest a benefit in reducing the incidence of IPPV. Further multicentre randomized controlled trials comparing elective nasal CPAP with "standard" methods of treatment are needed to clarify its clinical role. The sample size should be large enough to examine important clinical outcomes such as survival, short term and long term morbidity and costs of care. Infants should be stratified by gestational age at trial entry. Other issues that need to be taken into consideration would include whether the infants were inborn or outborn and outcomes of infants of lower gestational ages.
Dr Victor Han kindly provided additional information about his trial.
None
| Study | Methods | Participants | Interventions | Outcomes | Notes | Allocation concealment |
| Han 1987 | Blinding of randomization - yes. Opaque sealed envelopes were used. Blinding of intervention - no Complete followup - in 90% of cases (2 treatment and 3 control infants excluded due to congenital abnormalities or protocol violations) Blinding of outcome assessment - yes for chest xray, no for use of IPPV. | Characteristics : Preterm infants (n=87) of 32 weeks gestation or less and stratified by sex. Excluded were infants for whom there was insufficient time to obtain parental consent before birth, major congenital abnormalities and primary apnoea at birth necessitating immediate intubation and IPPV. | Experimental
: Nasopharyngeal CPAP of 6 cm water pressure applied at birth. Infants who
failed to improve [PaO2< 50mmHg in optimal CPAP (see notes) and FiO2
>0.8, apnea] were managed with endotracheal (ET) CPAP and then IPPV as
indicated by PaO2 < 50mmHg in FiO2 > 0.9, or pH < 7.2 mainly due
to PaCO2 >60mmHg, apnea (severity not defined) not controlled by ETCPAP Control : oxygen in a head box. Nasal CPAP given when PaO2< 50mmHg in FiO2 > 0.5, or apnea (given to 33%). Subsequent management similar to treatment group. Both groups of infants received an initial FiO2 ranging from 0.3 to 0.6. | Reported on 82 infants. Failed treatment included use of IPPV and other treatment, BPD at 28 days (oxygen therapy + abnormal chest xray - blindly assessed), neonatal death, pulmonary air leaks (no breakdown by pneumothorax vs other available), PDA, any IVH (breakdown by grade not available), subglottic stenosis, neonatal sepsis (blood culture +ve), NEC (Bell stage 2 or more), RLF (ROP grade 3 or 4). | Additional information provided by the author in
July 2002 on randomization, timing of deaths, definitions of outcomes - sepsis,
BPD, RLF, airleaks and diagnosis of IVH Optimal CPAP was measured according to the method described by Tanswell 1980 in which a lowering esophageal pressure is used to demonstrate opening of small airways. No mother received antenatal corticosteroids and postnatal surfactant therapy was not available. 280 subjects planned, sequential descriptive analysis (stopped early because of possible worse outcomes in treatment group) | A |
| Sandri 2004 | Blinding
of randomization- yes. Computer generated numbers stratified for each week
of gestational age. Randomised in blocks of 6. Blinding of treatment - no. Complete followup - yes. Blinding of outcome assessments - not stated. | Characteristics: Preterm infants (n=230) between 28 to 31.6 weeks gestation. | Experimental: Prophylactic nasal CPAP of 4-6 cm water pressure applied within 30 minutes of birth. Control: received nasal CPAP when the fraction of inspired oxygen (FiO2) in the hood was >0.4 for more than 30 minutes, to maintain transcutaneous oxygen saturation (Sp02)at the right hand between 93% and 96%. nCPAP was given through nasal prongs using the Infant Flow Driver system. Newborns receiving nCPAP at a pressure of 6 cm water pressure, requiring a Fi02 > 0.4 for more than 30 minutes to maintain Sp02 in the range 93-96% and showed radiological signs of RDS were endotracheally intubated , treated with surfactant and manually ventilated for 2-5 minutes. the infants were then extubated and placed on nCPAP if they had a good respiratory drive and maintained a satisfactory Sp02 value. Criteria for mechanical ventilation (IPPV) were: Persistence of a FiO2 requirement of >0.4 on nCPAP after surfactant administration, severe apnoea, PaCO2 >70 mmHg and pH < 7.2, FiO2 rapidly increasing above 0.8 even before 30 minutes. | Failed treatment included the use of surfactant, the need for IPPV within 7 days, air leaks, death at or before 7 days, death between 8 to 28 days, neonatal death, IVH > grade 2, PVL, NEC, Sepsis, Chronic lung disease at 36 weeks, PDA | A |
| Study | Reason for exclusion |
| Drew 1982 | This study examined elective intubation at birth followed by CPAP via the endotracheal tube vs selective intubation on clinical grounds. |
| Tooley 2003 | This study examined preterm babies with RDS who were electively intubated and given one dose of surfactant within 20 minutes or less after birth. These infants were then randomised to either continue with mechanical ventilation or to be extubated to nCPAP within one hour after birth. |
| Study | Trial name or title | Participants | Interventions | Outcomes | Starting date | Contact information | Notes |
| Morley 2001 | The COIN Trial. Nasal CPAP (continuing positive airways pressure) or lntubation for very preterm infants at birth. | Preterm infants 25 - 28 weeks who are spontaneously breathing but require respiratory support | CPAP at 8 cm H2O vs intubation and IPPV at birth | Primary: mortality before discharge or chronic lung disease at 36 weeks postmenstrual age Secondary: various measures of neonatal morbidity | 1st Feb.2001 | Professor Colin Morley Ph +61 3 9344 2524 Email: Colin@morleys.net | |
| Thomson 2002 | Early nasal CPAP with prophylactic surfactant as an alternative management for neonates at risk of respiratory distress syndrome. | Multicentre UK study of preterm infants 27 - 29 weeks gestation at risk of RDS | Four groups 1. Early nasal CPAP after prophylactic surfactant 2. Early nasal CPAP with or without rescue surfactant 3. Early IPPV with prophylactic surfactant 4. Conventional management on merit with or without rescue CPAP (any type), IPPV or surfactant. Infant Flow used for CPAP in 1 & 2 | Use of IPPV, chronic lung disease at 28 days and 36 weeks. Other: duration of IPPV, length of stay, IVH, pneumothorax | Recruitment completed. Published in abstract form only. | Dr Merran Thomson,Email merran.thomson@ic.ac.uk |
Han VKM, Beverley DW, Clarson C, Sumabat WO, Shaheed WA, Brabyn DG, Chance GW. Randomized controlled trial of very early continuous distending pressure in the management of preterm infants. Early Human Development 1987;15:21-32.
Sandri 2004 {published data only}
Sandri F, Ancora G, Lanzoni A, Tagliabue P,Colnaghi M, Ventura M L , Rinaldi M, Mondello I, Gancia P, Salvioli GP, Orzalesi M, Mosca F. Prophylactic nasal continueous positive airway pressure in newborns of 28-31 weeks gestation: multicentre randomised controlled clinical trial. Archives of Disease in Childhood Fetal and Neonatal Edition 2004;89:F394-8.
Drew JH. Immediate intubation at birth of the very low birth weight infant. American Journal of Diseaes of Children 1982;136:207-10.
Tooley 2003 {published data only}
Tooley J, Dyke M. Randomized study of nasal continuous positive airway pressure in the preterm infant with respiratory distress syndrome. Acta Paediatrica 2003;92:1170-4.
Morley C, Davis PGD, Doyle P. The COIN trial. Nasal CPAP (continuous positive airways pressure) or lntubation for very preterm infants at birth. A randomised controlled trial.
Thomson 2002 {unpublished data sought but not used}
Thomson MA, on behalf of the IFDAS Study Group. Early nasal CPAP + prophylactic surfactant for neonates at risk of RDS. The IFDAS trial. Pediatric Research 2001;50:304.
* Thomson MA. Early nasal continuous positive airways pressure (nCPAP) with prophylactic surfactant for neonates at risk of RDS. The IFDAS Multi-Centre trial. Pediatric Research 2002;51:379A.
* indicates the primary reference for the study
Avery ME, Tooley WH, Keller JB, Hurd SS, Bryan MH, Cotton RB et al. Is chronic lung disease in low birth weight infants preventable? A survey of eight centers. Pediatrics 1987;79:26-30.
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.
Gittermann MK, Fusch C, Gitterman AR, Regazzoni BM, Moessinger AC. Early nasal continuous positive airway pressure treatment reduces the need for intubation in very low weight infants. Europen Journal of Pediatrics 1997;156:384-8.
Ho JJ, Subramaniam P, Henderson-Smart DJ, Davis PG. Continuous distending pressure for respiratory distress syndrome in preterm infants. In: The Cochrane Database of Systematic Reviews, Issue 2, 2004.
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 2, 2004.
Jacobsen T, Gronvall J, Petersen S, Andersen GE. "Minitouch" treatment of very low-birth-weight infants. Acta Paediatrics 1993;82:934-8.
Jonsson B, Katz-Salamon M, Faxelius G, Broberger U, Lagercrantz H. Neonatal care of very-low-birthweight infants in special-care units and neonatal intensive-care units in Stockholm. Early nasal continuous positive airway pressure versus mechanical ventilation: gains and losses. Acta Paediatrica 1997;86(419 Suppl):4-10.
Lundstrom KE. Initial treatment of preterm infants - continuous positive airway pressure or ventilation? European Journal of Pediatrics 1996;155(2 Suppl):S25-9.
Tanswell AK, Clubb RA, Smith BT, Boston RW. Individualised continuous distending pressure applied within 6 hours of delivery in infants with respiratory distress syndrome. Archives of Disease in Childhood 1980;55:33-9.
Subramaniam P, Henderson-Smart DJ, Davis PG. Prophylactic nasal continuous positive airways pressure for preventing morbidity and mortality in very preterm infants. In: The Cochrane Database of Systematic Reviews, Issue 4, 1998.
Subramaniam P, Henderson-Smart DJ, Davis PG. Prophylactic nasal continuous positive airways pressure for preventing morbidity and mortality in very preterm infants. In: The Cochrane Database of Systematic Reviews, Issue 2, 2002.
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
| 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. |