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Meta-Analysis
. 2021 Oct 18;10(10):CD001243.
doi: 10.1002/14651858.CD001243.pub4.

Prophylactic or very early initiation of continuous positive airway pressure (CPAP) for preterm infants

Prema Subramaniam  1 , Jacqueline J Ho  2 , Peter G Davis  3   4   5
Affiliations
Meta-Analysis

Prophylactic or very early initiation of continuous positive airway pressure (CPAP) for preterm infants

Prema Subramaniam et al. Cochrane Database Syst Rev. .

Abstract

Background: Cohort studies have suggested that nasal continuous positive airway pressure (CPAP) starting in the immediate postnatal period before the onset of respiratory disease (prophylactic CPAP) may be beneficial in reducing the need for intubation and intermittent positive pressure ventilation (IPPV), and in preventing bronchopulmonary dysplasia (BPD), in preterm or low birth weight infants.

Objectives: To determine if prophylactic nasal CPAP (started within the first 15 minutes) or very early nasal CPAP regardless of respiratory status (started within the first hour of life), reduces the use of mechanical ventilation and the incidence of bronchopulmonary dysplasia without any adverse effects in preterm infants.

Search methods: A comprehensive search was run on 6 November 2020 in the Cochrane Central Register of Controlled Trials (CENTRAL via CRS Web) and MEDLINE via Ovid. We also searched the reference lists of retrieved studies.

Selection criteria: We included all randomised controlled trials (RCTs) and quasi-RCTs in preterm infants (under 37 weeks of gestation). We included trials if they compared prophylactic nasal CPAP (started within the first 15 minutes) or very early nasal CPAP (started within the first hour of life) in infants with minimal signs of respiratory distress with 'supportive care', such as supplemental oxygen therapy, standard nasal cannula, or mechanical ventilation. We excluded studies where prophylactic CPAP was compared with CPAP along with co-interventions.

Data collection and analysis: We used the standard methods of Cochrane Neonatal, including independent study selection, assessment of trial quality, and extraction of data by two review authors.

Main results: We included eight trials (seven from the previous version of the review and one new study), recruiting 3201 babies, in the meta-analysis. Four trials, involving 765 babies, compared CPAP with supportive care, and three trials (2364 babies) compared CPAP with mechanical ventilation. One trial (72 babies) compared prophylactic CPAP with very early CPAP. Apart from a lack of blinding of the intervention, we judged seven studies to have a low risk of bias. However, one study had a high risk of selection bias. Prophylactic or very early CPAP compared to supportive care There may be a reduction in failed treatment (risk ratio (RR) 0.6, 95% confidence interval (CI) 0.49 to 0.74; risk difference (RD) -0.16, 95% CI -0.34 to 0.02; 4 studies, 765 infants; very low certainty evidence). CPAP possibly reduces BPD at 36 weeks (RR 0.76, 95% CI 0.51 to 1.14; 3 studies, 683 infants, moderate certainty evidence); there may be little or no difference in death (RR 1.04, 95% CI 0.56 to 1.93; 4 studies, 765 infants; moderate certainty evidence). Prophylactic CPAP may reduce the composite outcome of death or BPD (RR 0.69, 95% CI 0.40 to 1.19; 1 study, 256 infants; low certainty evidence). There may be no difference in pulmonary air leak (pneumothorax) (RR 0.75, 95% CI 0.35 to 1.16; 3 studies, 568 infants; low certainty evidence), or intraventricular haemorrhage (IVH) Grade 3 or 4 (RR 0.96, 95% CI 0.39 to 2.37; 2 studies, 486 infants; moderate certainty evidence). Neurodevelopmental impairment was not reported in any of the studies. Prophylactic or very early CPAP compared to mechanical ventilation There was probably a reduction in the incidence of BPD at 36 weeks (RR 0.89, 95% CI 0.8 to 0.99; RD -0.04, 95% CI -0.08 to 0.00; 3 studies, 2150 infants; moderate certainty evidence); and death or BPD (RR 0.89, 95% CI 0.81 to 0.97; RD -0.05, 95% CI -0.09 to 0.01; 3 studies, 2358 infants; moderate certainty evidence). There was also probably a reduction in the need for mechanical ventilation (failed treatment) (RR 0.49, 95% CI 0.45 to 0.54; RD -0.50, 95% CI -0.54 to -0.45; 2 studies, 1042 infants; moderate certainty evidence). There was probably a reduction in the incidence of death (RR 0.82, 95% CI 0.66 to 1.03; 3 studies, 2358 infants; moderate certainty evidence); pulmonary air leak (pneumothorax) (RR 1.24, 95% CI 0.91 to 1.69; 3 studies, 2357 infants; low certainty evidence); and IVH Grade 3 or 4 (RR 1.09, 95% CI 0.86 to 1.39; 3 studies, 2301 infants; moderate certainty evidence). One study in this comparison reported that there was probably little or no difference between the groups in the incidence of neurodevelopmental impairment at 18 to 22 months (RR 0.91, 95% CI 0.62 to 1.32; 976 infants; moderate certainty evidence). Prophylactic CPAP compared with very early CPAP There was one study in this comparison. We are very uncertain whether there is any difference in the incidence of BPD (RR 0.5, 95% CI 0.05 to 5.27; very low certainty evidence). The combined outcome of death and BPD was not reported, and failed treatment was reported but without data. There may have been little to no effect on death (RR 0.75, 95% CI 0.29 to1.94; 1 study, 72 infants; very low certainty evidence). Intraventricular haemorrhage Grade 3 or 4 and neurodevelopmental outcomes were not reported in this study. Pulmonary air leak (pneumothorax) was reported in this study, but there were no events in either group.

Authors' conclusions: For preterm and very preterm infants, there is insufficient evidence to evaluate prophylactic CPAP compared to oxygen therapy and other supportive care. When compared to mechanical ventilation, prophylactic nasal CPAP in very preterm infants reduces the incidence of BPD, the combined outcome of death and BPD, and mechanical ventilation. There is probably no difference in neurodevelopmental impairment at 18 to 22 months of age. When prophylactic CPAP is compared to early CPAP, we are very uncertain about whether there is any difference between prophylactic and very early CPAP. There is no information about the effect of prophylactic or very early CPAP in late preterm infants. There is one study awaiting classification.

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Conflict of interest statement

Prema Subramaniam has declared no conflicts.

Jacqueline J Ho has worked as a Consultant Neonatologist for the Ministry of Health, Malaysia, as a Neonatal Unit Director.

Peter G Davis is a Neonatologist who receives project and salary support from the Australian National Health and Medical Research Council. He was involved in conducting an included study, the COIN trial (Morley 2008). This study was funded by the Australian National Health and Medical Research Council. JJH and PS independently extracted the data from the COIN study.

Figures

1
1
Study flow diagram: review update
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
1.1
1.1. Analysis
Comparison 1: Prophylactic CPAP vs supportive care, Outcome 1: Failed treatment
1.2
1.2. Analysis
Comparison 1: Prophylactic CPAP vs supportive care, Outcome 2: Bronchopulmonary dysplasia at 28 days
1.3
1.3. Analysis
Comparison 1: Prophylactic CPAP vs supportive care, Outcome 3: Bronchopulmonary dysplasia at 28 days
1.4
1.4. Analysis
Comparison 1: Prophylactic CPAP vs supportive care, Outcome 4: Bronchopulmonary dysplasia at 36 weeks
1.5
1.5. Analysis
Comparison 1: Prophylactic CPAP vs supportive care, Outcome 5: Death at anytime
1.6
1.6. Analysis
Comparison 1: Prophylactic CPAP vs supportive care, Outcome 6: Death or bronchopulmonary dysplasia
1.7
1.7. Analysis
Comparison 1: Prophylactic CPAP vs supportive care, Outcome 7: Use of surfactant
1.8
1.8. Analysis
Comparison 1: Prophylactic CPAP vs supportive care, Outcome 8: Pulmonary airleak (Pneumothorax)
1.9
1.9. Analysis
Comparison 1: Prophylactic CPAP vs supportive care, Outcome 9: Local trauma
1.10
1.10. Analysis
Comparison 1: Prophylactic CPAP vs supportive care, Outcome 10: IVH (any grade)
1.11
1.11. Analysis
Comparison 1: Prophylactic CPAP vs supportive care, Outcome 11: IVH grade 3 or 4
1.12
1.12. Analysis
Comparison 1: Prophylactic CPAP vs supportive care, Outcome 12: Periventricular leukomalacia
1.13
1.13. Analysis
Comparison 1: Prophylactic CPAP vs supportive care, Outcome 13: Necrotising enterocolitis
1.14
1.14. Analysis
Comparison 1: Prophylactic CPAP vs supportive care, Outcome 14: Late onset systemic infection
1.15
1.15. Analysis
Comparison 1: Prophylactic CPAP vs supportive care, Outcome 15: Retinopathy of prematurity grade 3 or 4
2.1
2.1. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 1: Bronchopulmonary dysplasia (BPD) at 28 days
2.2
2.2. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 2: Bronchopulmonary dysplasia at 36 weeks
2.3
2.3. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 3: Bronchopulmonary dysplasia at 36 weeks (subgroup analysis by CPAP pressure)
2.4
2.4. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 4: Death at anytime (subgroups by CPAP pressure)
2.5
2.5. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 5: Death at anytime (subgroups by gestation)
2.6
2.6. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 6: Death or bronchopulmonary dysplasia
2.7
2.7. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 7: Death or bronchopulmonary dysplasia
2.8
2.8. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 8: Failed Treatment (Mechanical Ventilation)
2.9
2.9. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 9: Use of surfactant
2.10
2.10. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 10: Pulmonary airleak (pneumothorax)
2.11
2.11. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 11: IVH (any grade)
2.12
2.12. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 12: IVH grade 3 or 4
2.13
2.13. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 13: Periventricular leukomalacia
2.14
2.14. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 14: Necrotising enterocolitis
2.15
2.15. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 15: Late onset systemic infection
2.16
2.16. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 16: Retinopathy of prematurity grade 3 or 4
2.17
2.17. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 17: Neurodevelopmental Impairment at 18 to 22 months corrected age
2.18
2.18. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 18: Death or neurodevelopment impairment at 18 to 22 months corrected age
2.19
2.19. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 19: Moderate or severe cerebral palsy
2.20
2.20. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 20: Bilateral blindness
2.21
2.21. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 21: Hearing Impairment
2.22
2.22. Analysis
Comparison 2: Prophylactic CPAP vs mechanical ventilation, Outcome 22: Cognitive score < 70
3.1
3.1. Analysis
Comparison 3: Prophylactic vs very early CPAP, Outcome 1: Bronchopulmonary dysplasia at 28 days
3.2
3.2. Analysis
Comparison 3: Prophylactic vs very early CPAP, Outcome 2: Death at anytime
3.3
3.3. Analysis
Comparison 3: Prophylactic vs very early CPAP, Outcome 3: Use of surfactant
3.4
3.4. Analysis
Comparison 3: Prophylactic vs very early CPAP, Outcome 4: IVH (any grade)
3.5
3.5. Analysis
Comparison 3: Prophylactic vs very early CPAP, Outcome 5: Late onset systemic infection
See this image and copyright information in PMC

Update of

References

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Drew 1982 {published and unpublished data}
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References to other published versions of this review

Subramaniam 1998
    1. Subramaniam P, Henderson-Smart DJ, Davis PG. Prophylactic nasal continuous positive airways pressure for preventing morbidity and mortality in very preterm infants. Cochrane Database of Systematic Reviews 1998, Issue 4. Art. No: CD001243. [DOI: 10.1002/14651858.CD001243] - DOI - PubMed
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