Premature babies given breathing support within the first hour of life with continuous positive airway pressure (CPAP) – where air is pushed into the baby’s nose at a constant pressure and the baby breathes by itself – compared to oxygen alone, may be less likely to be put on a ventilator - where a tube is inserted into the baby’s lungs and a machine breathes for the baby.
CPAP in the first hour after birth compared to a ventilator probably leads to less lung damage, fewer deaths, and less need for babies to be put on a ventilator.
One small study looked at the effect of the timing of CPAP after birth (up to 15 minutes compared to up to 1 hour), so there was not enough evidence to make a judgement regarding timing.
What is continuous positive airway pressure?
Continuous positive airway pressure (CPAP) helps people with breathing difficulties by pushing air into their lungs through the nose at a constant pressure. Air is delivered through a mask that fits over the nose, or prongs that sit in the nostrils. CPAP is less invasive than mechanical ventilation, when a tube is put down the throat into the lungs and a machine (a ventilator) ‘breathes’ for the patient. CPAP provides more breathing support than just giving oxygen.
How does CPAP help premature babies?
Premature babies are those babies born before 37 weeks of development (gestation). They may have trouble breathing because their lungs are not fully developed. This is called ‘respiratory distress syndrome’ (RDS). Premature babies with non-severe RDS may be treated with warmth, fluids, calories, and oxygen. Babies with severe RDS are given breathing support with CPAP or a ventilator. Babies breathe by themselves with CPAP, but the pressure of the stream of air that CPAP delivers keeps the baby’s airways open between breaths. Babies on CPAP avoid being put on ventilators, which can cause lung damage, such as bronchopulmonary dysplasia (BPD).
CPAP can be given within the first 15 minutes after birth (preventive CPAP), or up to an hour after birth as therapy if babies show early signs of RDS (very early CPAP).
What did we want to find out?
We wanted to know if preventive CPAP and very early CPAP are effective in preventing RDS in premature babies. We were interested in:
- how many babies had BPD;
- whether CPAP successfully supported babies’ breathing, or if they needed to be put on a ventilator;
- how many babies died; and
- the combined number of babies who died or developed BPD.
What did we do?
We searched for studies that investigated CPAP given to premature babies 15 minutes after birth, whether or not they showed signs of RDS, and to premature babies who showed early signs of RDS up to 1 hour after birth. Studies could look at:
- CPAP compared to supportive care, which includes supplemental oxygen;
- CPAP compared to putting babies on a ventilator; and
- preventive CPAP compared to very early CPAP.
What did we find?
We found 8 studies with 3201 babies in total ranging from 24 to 32 weeks gestation:
- 4 studies with 765 babies compared CPAP with supportive care;
- 3 studies with 2364 babies compared CPAP with ventilation; and
- 1 study with 72 babies compared preventive CPAP with very early CPAP.
Studies took place in high- and middle-income countries: Argentina, Australia, Brazil, Canada, Chile, Italy, New Zealand, Paraguay, Peru, Uruguay, and the USA. Babies were very or extremely preterm, or very low birth weight (less than 1500 grams); no studies included late preterm babies or low birthweight babies.
Compared to supportive care, CPAP:
- makes little to no difference to BPD up to 28 days after birth;
- may result in fewer babies needing to be put on a ventilator; and
- probably makes little to no difference to combined numbers of deaths and BPD.
Compared to a ventilator, CPAP:
- probably reduces BPD up to 36 weeks after birth;
- probably reduces the need for babies to be put on a ventilator by almost half; and
reduces the combined numbers of deaths and BPD.
Due to insufficient evidence, we don't know whether preventive CPAP compared to very early CPAP makes any difference to BPD up to 28 days after birth, reduces or increases the number of deaths up to 28 days after birth, or reduces the need for babies to be put on a ventilator.
What are the limitations of the evidence?
We have limited evidence about CPAP compared to supportive care. CPAP compared to ventilators probably reduces BPD and combined numbers of death and BPD. We are very uncertain about the effect of preventive CPAP compared with very early CPAP because there was one small study that lacked the details we needed.
How up to date is this evidence?
This updates our previous review. The evidence is up to date to 6 November 2020.
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.
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.
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.
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.
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.
We used the standard methods of Cochrane Neonatal, including independent study selection, assessment of trial quality, and extraction of data by two review authors.
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.