Review question
We wanted to find out whether for preterm infants in respiratory distress, applying continuous positive airway pressure (CPAP) early would result in increased benefit and less harm than if it were applied later.
Background
Preterm babies often lack surfactant, a detergent-like substance produced by the lung. Lack of surfactant causes their lungs to fail to expand properly at birth and results in the need for greater effort in breathing. If left untreated, the breathing difficulty progressively worsens and may lead to lung damage. CPAP improves expansion of the lung, making it easier for the baby to breathe, and might reduce the need for intermittent positive-pressure ventilation (IPPV), a form of respiratory support that carries greater risks, including the risk of developing a type of lung damage called bronchopulmonary dysplasia (BDP). CPAP might also reduce the risk of the baby dying from respiratory distress. CPAP is applied through a face mask, a nasal mask, or prongs into the nostrils.
Study characteristics
The search is up-to-date as of June 2020. We found four small studies including a total of 119 babies. All four studies were performed in the 1970s or early 1980s, when the use of antenatal steroids (given to the mother to help a preterm baby's lung to become more mature) was uncommon.
Key results
From these four small studies, we are very uncertain whether early CPAP provides any benefit or whether it causes any harm.
Certainty of evidence
All four included studies had weaknesses in the way they were conducted, and all were very small. In addition, because they were old studies, study results might not apply to the current care of preterm infants. Therefore, we assessed the certainty of evidence as very low.
All four small trials included in this review were performed in the 1970s or the early 1980s, and we are very uncertain whether early application of CPAP confers clinical benefit in the treatment of respiratory distress, or whether it is associated with any adverse effects.
Further trials should be directed towards establishing the appropriate level of CPAP and the timing and method of administration of surfactant when used along with CPAP.
The application of continuous positive airway pressure (CPAP) has been shown to have some benefits in the treatment of preterm infants with respiratory distress. CPAP has the potential to reduce lung damage, particularly if applied early before atelectasis has occurred. Early application may better conserve an infant's own surfactant stores and consequently may be more effective than later application.
• To determine if early compared with delayed initiation of CPAP results in lower mortality and reduced need for intermittent positive-pressure ventilation in preterm infants in respiratory distress
○ Subgroup analyses were planned a priori on the basis of weight (with subdivisions at 1000 grams and 1500 grams), gestation (with subdivisions at 28 and 32 weeks), and according to whether surfactant was used
▫ Sensitivity analyses based on trial quality were also planned
○ For this update, we have excluded trials using continuous negative pressure
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 6), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations Daily and Versions(R); and the Cumulative Index to Nursing and Allied Health Literatue (CINAHL), on 30 June 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs.
We included trials that used random or quasi-random allocation to either early or delayed CPAP for spontaneously breathing preterm infants in respiratory distress.
We used the standard methods of Cochrane and Cochrane Neonatal, including independent assessment of trial quality and extraction of data by two review authors. We used the GRADE approach to assess the certainty of evidence.
We found four studies that recruited a total of 119 infants. Two were quasi-randomised, and the other two did not provide details on the method of randomisation or allocation used. None of these studies used blinding of the intervention or the outcome assessor. Evidence showed uncertainty about whether early CPAP has an effect on subsequent use of intermittent positive-pressure ventilation (IPPV) (typical risk ratio (RR) 0.77, 95% confidence interval (CI) 0.43 to 1.38; typical risk difference (RD) -0.08, 95% CI -0.23 to 0.08; I² = 0%, 4 studies, 119 infants; very low-certainty evidence) or mortality (typical RR 0.93, 95% CI 0.43 to 2.03; typical RD -0.02, 95% CI -0.15 to 0.12; I² = 33%, 4 studies, 119 infants; very low-certainty evidence). The outcome 'failed treatment' was not reported in any of these studies. There was an uncertain effect on air leak (pneumothorax) (typical RR 1.09, 95% CI 0.39 to 3.04, I² = 0%, 3 studies, 98 infants; very low-certainty evidence). No trials reported intraventricular haemorrhage or necrotising enterocolitis. No cases of retinopathy of prematurity were reported in one study (21 infants). One case of bronchopulmonary dysplasia was reported in each group in one study involving 29 infants. Long-term outcomes were not reported.