Review question: we wanted to know whether using continuous positive airways pressure (CPAP) compared with oxygen alone would safely reduce death or the use of mechanical ventilation in preterm infants with breathing difficulties.
Background: breathing difficulties due to lung immaturity are the most common cause of death in preterm infants. These breathing difficulties are often mild soon after birth and worsen over the first hours or days of life. The usual care for mildly ill babies is to use oxygen. This may be given via a mask, a tube placed in the nose or via a headbox (a Perspex head chamber with a flow of oxygen and air). Sicker babies require a mechanical ventilator, which breaths for the baby via a tube inserted into the baby's lungs (endotracheal tube). However, ventilators, while they may save lives, can damage the lungs, particularly immature lungs. In preterm infants this damage is known as bronchopulmonary dysplasia (BPD). A complication of ventilation is collapsed lung (pneumothorax), where air leaks from the lung through a hole into the space between the lung and the pleura (its covering).
CPAP is a relatively simple way of providing breathing assistance to a baby that might reduce lung damage. This method relies on the baby continuing to breath. A continuous pressure is applied by means of a tube in the nostrils (binasal prong), a mask covering just the nose (nasal mask), a face mask or by a tube placed in the lungs (endotracheal tube). This opens the baby's airways and makes breathing easier.
Continuous negative pressure (CNP) is an alternative to CPAP. The baby's body is encased in a chamber that expands the lungs and makes breathing easier. CNP is cumbersome and CPAP has superseded it. We have not included CNP studies in this review update.
Search dates: the search was conducted on 30 June 2020.
Study characteristics: we included five trials that enrolled 322 babies.
Three studies were conducted in the 1970s, one in 2007 and one in 2020 in a low-resource setting. Few if any of the infants were below 1000 g birthweight. All studies reported whether CPAP reduced the death or failed treatment (which included either death or ventilation). Four studies reported whether CPAP reduced the use of ventilators.
Key results: we found about half the babies on supplemental oxygen alone failed treatment (either died or were ventilated), such that if 1000 babies were treated, 519 would fail treatment. CPAP reduced this to about a third, such that if 1000 babies were treated, 332 would fail treatment or between 259 and 425 per 1000. However, because of risk of bias, differences between the studies, and small sample size and setting (more than 40 years ago for three studies), we are very uncertain about this effect. We are also uncertain about whether ventilation alone was reduced. Death is likely to be reduced from 235 per 1000 to between 80 per 1000 and 195 per 1000.
Pneumothorax may be more common with CPAP. There was insufficient information to show whether there was a difference in the rate of BPD. We do not have any information about other important complications or whether there is any difference later in childhood.
In preterm infants with respiratory distress, the application of CPAP is associated with reduced respiratory failure, use of mechanical ventilation and mortality and an increased rate of pneumothorax compared to spontaneous breathing with supplemental oxygen as necessary. Three out of five of these trials were conducted in the 1970s. Therefore, the applicability of these results to current practice is unclear. Further studies in resource-poor settings should be considered and research to determine the most appropriate pressure level needs to be considered.
Respiratory distress, particularly respiratory distress syndrome (RDS), is the single most important cause of morbidity and mortality in preterm infants. In infants with progressive respiratory insufficiency, intermittent positive pressure ventilation (IPPV) with surfactant has been the usual treatment, but it is invasive, potentially resulting in airway and lung injury. Continuous positive airway pressure (CPAP) has been used for the prevention and treatment of respiratory distress, as well as for the prevention of apnoea, and in weaning from IPPV. Its use in the treatment of RDS might reduce the need for IPPV and its sequelae.
To determine the effect of continuous distending pressure in the form of CPAP on the need for IPPV and associated morbidity in spontaneously breathing preterm infants with respiratory distress.
We used the standard strategy of Cochrane Neonatal to search CENTRAL (2020, Issue 6); Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions; and CINAHL on 30 June 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
All randomised or quasi-randomised trials of preterm infants with respiratory distress were eligible. Interventions were CPAP by mask, nasal prong, nasopharyngeal tube or endotracheal tube, compared with spontaneous breathing with supplemental oxygen as necessary.
We used standard methods of Cochrane and its Neonatal Review Group, including independent assessment of risk of bias and extraction of data by two review authors. We used the GRADE approach to assess the certainty of evidence.
Subgroup analyses were planned on the basis of birth weight (greater than or less than 1000 g or 1500 g), gestational age (groups divided at about 28 weeks and 32 weeks), timing of application (early versus late in the course of respiratory distress), pressure applied (high versus low) and trial setting (tertiary compared with non-tertiary hospitals; high income compared with low income)
We included five studies involving 322 infants; two studies used face mask CPAP, two studies used nasal CPAP and one study used endotracheal CPAP and continuing negative pressure for a small number of less ill babies. For this update, we included one new trial.
CPAP was associated with lower risk of treatment failure (death or use of assisted ventilation) (typical risk ratio (RR) 0.64, 95% confidence interval (CI) 0.50 to 0.82; typical risk difference (RD) –0.19, 95% CI –0.28 to –0.09; number needed to treat for an additional beneficial outcome (NNTB) 6, 95% CI 4 to 11; I2 = 50%; 5 studies, 322 infants; very low-certainty evidence), lower use of ventilatory assistance (typical RR 0.72, 95% CI 0.54 to 0.96; typical RD –0.13, 95% CI –0.25 to –0.02; NNTB 8, 95% CI 4 to 50; I2 = 55%; very low-certainty evidence) and lower overall mortality (typical RR 0.53, 95% CI 0.34 to 0.83; typical RD –0.11, 95% CI –0.18 to –0.04; NNTB 9, 95% CI 2 to 13; I2 = 0%; 5 studies, 322 infants; moderate-certainty evidence). CPAP was associated with increased risk of pneumothorax (typical RR 2.48, 95% CI 1.16 to 5.30; typical RD 0.09, 95% CI 0.02 to 0.16; number needed to treat for an additional harmful outcome (NNTH) 11, 95% CI 7 to 50; I2 = 0%; 4 studies, 274 infants; low-certainty evidence). There was no evidence of a difference in bronchopulmonary dysplasia, defined as oxygen dependency at 28 days (RR 1.04, 95% CI 0.35 to 3.13; I2 = 0%; 2 studies, 209 infants; very low-certainty evidence). The trials did not report use of surfactant, intraventricular haemorrhage, retinopathy of prematurity, necrotising enterocolitis and neurodevelopment outcomes in childhood.