Key messages
We did not find any study that compared CPAP with supportive care for apnoea of prematurity.
We found four studies comparing one type of CPAP to another. The studies were small and the care given by healthcare workers may have been influenced by knowing which treatment the baby was receiving. Therefore, we don’t know from these studies whether there is any difference between different types of CPAP for reducing apnoea in babies born too early.
What is apnoea of prematurity?
Babies born early (preterm) may experience prolonged pauses in their breathing. In a baby born too early, we call such pauses apnoea of prematurity. Apnoea may be due to immaturity of the mechanisms controlling breathing or to weakness of the muscles that keep their airway open during breathing. In severe apnoea the baby’s heart rate will slow and there will be a drop in the level of oxygen. If this happens too often it may affect the baby’s brain development. When babies have apnoea, supportive care is usually given. This may be in the form of stimulation, by stroking the baby or moving their limbs, providing oxygen, or both.
What is CPAP?
Continuous positive airway pressure (CPAP) is a form of breathing support, often referred to as a type of non-invasive ventilation. The continuous pressure is applied usually through a nose piece, allowing the baby to continue to breathe by themselves but making breathing easier. This is probably because the positive pressure that is applied helps to keep the airway open.
What did we want to find out?
We wanted to find out whether using CPAP in preterm babies might reduce apnoea or the need for a more invasive form of treatment such as mechanical ventilation, i.e. using a machine to do the breathing for the baby. We also wanted to know whether any particular method of applying CPAP was more effective.
What did we do?
We searched for studies that included preterm babies where the researchers thought CPAP was necessary for apnoea of prematurity. We included studies that compared CPAP with supportive care (such as stimulation, oxygen, or both) or studies that compared different types of CPAP.
What did we find?
We did not find any studies that compared CPAP with supportive care. We found four small studies, involving 138 babies. They compared two different forms of CPAP. There were three comparisons with only one study in each comparison and one study did not provide any useful data. The duration of CPAP in the four studies was between 4 and 48 hours. From these four studies, we do not know whether there is any difference between different forms of CPAP. This is because each comparison had only one study, the results were very imprecise because the studies were small, and the care given by the healthcare workers might have been influenced by their awareness of which treatment the baby was receiving.
How up-to-date is the evidence?
The evidence is up-to-date to 6 September 2022.
Due to the limited available evidence, we are very uncertain whether any CPAP device is more effective than other forms of supportive care, other CPAP devices, or mechanical ventilation for the prevention and treatment of AoP. The devices used in these studies included two types of variable flow CPAP device: bubble CPAP and ventilator CPAP. For each comparison, data were only available from a single study. There are theoretical reasons why these devices might have different effects on AoP, therefore further trials are indicated.
Apnoea of prematurity (AoP) is defined as a pause in breathing for 20 seconds or longer, or for less than 20 seconds when accompanied by bradycardia and hypoxaemia, in a preterm infant. An association between the severity of apnoea and neurodevelopmental delay has been reported. Continuous positive airway pressure (CPAP) is a form of non-invasive ventilatory assistance that has been shown to be relatively safe and effective in preventing and treating respiratory distress among preterm infants. It is less clear whether CPAP treatment is safe and effective in the prevention and treatment of AoP.
1. To assess the effects of CPAP on AoP in preterm infants (this may be compared to supportive care or mechanical ventilation).
2. To assess the effects of different CPAP delivery systems on AoP in preterm infants.
Searches were conducted in September 2022 in the following databases: Cochrane Library, MEDLINE, Embase, and CINAHL. We also searched clinical trial registries and the reference lists of studies selected for inclusion.
We included all randomised and quasi-randomised controlled trials (RCTs) in which researchers determined that CPAP was necessary for AoP in preterm infants (born before 37 weeks). Cross-over studies were also included, provided sufficient data were available for analysis.
We used the standard methods of Cochrane and Cochrane Neonatal, including independent assessment of risk of bias and extraction of data by at least two review authors. Discrepancies were resolved by involvement of a third author. We used the GRADE approach to assess the certainty of evidence for the following outcomes: 1) failed CPAP; 2) apnoea; 3) adverse effects of CPAP.
We included four single-centre trials conducted in Malaysia, Spain, Germany, and North America, involving 138 infants with a mean/median gestation of 26 to 28 weeks. Two studies were parallel-group RCTs and two were cross-over trials. None of the studies compared CPAP with supportive care. All trials compared one form of CPAP with another. Two compared a variable flow device with ventilator CPAP, one compared two different variable flow devices, and one compared a variable flow device with bubble CPAP. Interventions were administered for periods ranging between six and 48 hours, with pressures between 4 and 6 cm H2O. We assessed all trials as having a high risk of bias for blinding of participants and personnel, and two studies for blinding of outcome assessors. We found a high risk of a carry-over effect in two studies where the washout period was not adequately described, and a high risk of bias in a study that appeared to use an analysis method not generally accepted for cross-over studies.
Comparison 1. CPAP and supportive care compared to supportive care alone
We did not identify any study for inclusion in this comparison.
Comparison 2. CPAP delivered by different types of devices
2a. Variable flow compared to ventilator CPAP
Two studies were included in this comparison. We are very uncertain whether there is any difference in the incidence of failed CPAP, defined as the need for mechanical ventilation (risk ratio (RR) 0.16, 95% confidence interval (CI) 0.01 to 2.90; 1 study, 26 participants; very low-certainty). We are very uncertain whether there is any difference in the frequency of apnoea events (mean difference (MD) per four-hour interval -0.10, 95% CI -1.30 to 1.10; 1 study, 26 participants; very low-certainty). We are uncertain whether there is any difference in adverse events. Neurodevelopmental outcomes were not reported.
2b. Variable flow compared to bubble CPAP
We included one study in this comparison, but it did not report our pre-specified outcomes.
2c. Infant Flow variable flow CPAP compared to Medijet variable flow CPAP
We are very uncertain whether there is any difference in the incidence of failed CPAP (RR 2.62, 95% CI 0.91 to 7.53; 1 study, 80 participants; very low-certainty). The frequency of apnoea was not reported, and we do not know whether there is any difference in adverse events. Neurodevelopmental outcomes were not reported.
Comparison 3. CPAP compared to mechanical ventilation
We did not identify any studies for inclusion in this comparison.