Nasal continuous positive airways pressure started immediately after birth for preventing illness and death in very preterm infants

Review Question: If CPAP were started immediately after birth before the onset of respiratory distress would it reduce the need for mechanical ventilation and would it reduce bronchopulmonary dysplasia (BPD)?

Background: Preterm babies may have breathing difficulty due to immature lungs, a condition known as Respiratory Distress Syndrome (RDS).The usual treatment is to assist their breathing with the help of a mechanical ventilator. Recent studies have shown that these babies are further helped by instilling surfactant into the 'breathing tube' while giving support with mechanical ventilation. However using a mechanical ventilator has its own dangers, the most important being BPD, a form of lung damage that occurs when preterm lungs are exposed to mechanical ventilation. Nasal continuous positive airway pressure (nasal CPAP) is a form of respiratory support delivered either via tubes inserted into the nostrils or a mask placed over the nose, leaving the mouth free. It is designed to ease the breathing effort of babies who can breathe on their own and has been found to help preterm babies if it is used to treat established RDS.

Search Date: The evidence is current to January 2016.

Study Characteristics: Randomised controlled trials of preterm babies below 32 weeks' gestation or below 1500 grams at birth who were treated with CPAP applied within the first 15 minutes of life compared with babies who were given either (1) routine supportive care such as oxygen therapy or (2) mechanical ventilation.

Results: There were a total of seven studies involving 3123 infants. They were generally of moderate quality. Parents and care-givers would have known which treatment group the babies were in, but we judged this not to be important for most outcomes measured. In the four studies (765 babies) comparing CPAP with supportive care, CPAP resulted in fewer infants requiring further breathing assistance but there was considerable inconsistency between the studies. In the three studies (2354 babies) that compared CPAP with assisted ventilation with or without surfactant, CPAP resulted in a small but clinically important reduction in BPD and the combined outcome of BPD and mortality. There was a reduction in the need for mechanical ventilation and the use of surfactant in the CPAP group.

Authors' conclusions: 

There is insufficient evidence to evaluate prophylactic CPAP compared to oxygen therapy and other supportive care. However when compared to mechanical ventilation prophylactic nasal CPAP in very preterm infants reduces the need for mechanical ventilation and surfactant and also reduces the incidence of BPD and death or BPD.

Read the full abstract...

Cohort studies have suggested that nasal continuous positive airways 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 soon after birth regardless of respiratory status in the very preterm or very low birth weight infant reduces the use of IPPV and the incidence of bronchopulmonary dysplasia (BPD) without adverse effects.

Search strategy: 

We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 1), MEDLINE via PubMed (1966 to 31 January 2016), EMBASE (1980 to 31 January 2016), and CINAHL (1982 to 31 January 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.

Selection criteria: 

All trials using random or quasi-random patient allocation of very preterm infants (under 32 weeks' gestation) or less than 1500 grams at birth were eligible. We included trials if they compared prophylactic nasal CPAP started soon after birth regardless of the respiratory status of the infant with 'standard' methods of treatment such as IPPV, oxygen therapy or supportive treatment. We excluded studies where prophylactic CPAP was compared with CPAP along with other interventions.

Data collection and analysis: 

We used the standard methods of Cochrane and its Neonatal Review Group, including independent study selection, assessment of trial quality and extraction of data by two authors. Data were analysed using risk ratio (RR) and the meta-analysis was performed using a fixed-effect model.

Main results: 

Seven trials recruiting 3123 babies were included in the meta-analysis. Four trials recruiting 765 babies compared CPAP with supportive care and three trials (2364 infants) compared CPAP with mechanical ventilation. Apart from a lack of blinding of the intervention all studies were of low risk of bias.

In the comparison of CPAP with supportive care there was a reduction in failed treatment (typical risk ratio (RR) 0.66, 95% confidence interval (CI) 0.45 to 0.98; typical risk difference (RD) −0.16, 95% CI −0.34 to 0.02; 4 studies, 765 infants, very low quality evidence). There was no reduction in bronchopulmonary dysplasia (BPD) or mortality.

In trials comparing CPAP with assisted ventilation with or without surfactant, CPAP resulted in a small but clinically significant reduction in the incidence of BPD at 36 weeks, (typical RR 0.89, 95% CI 0.79 to 0.99; typical RD −0.04, 95% CI −0.08 to 0.00; 3 studies, 772 infants, moderate-quality evidence); and death or BPD (typical RR 0.89, 95% CI 0.81 to 0.97; typical RD −0.05, 95% CI −0.09 to 0.01; 3 studies, 1042 infants, moderate-quality evidence). There was also a clinically important reduction in the need for mechanical ventilation (typical RR 0.50, 95% CI 0.42 to 0.59; typical RD −0.49, 95% CI −0.59 to −0.39; 2 studies, 760 infants, moderate-quality evidence); and the use of surfactant in the CPAP group (typical RR 0.54, 95% CI 0.40 to 0.73; typical RD −0.41, 95% CI −0.54 to −0.28; 3 studies, 1744 infants, moderate-quality evidence).