Prophylactic nasal continuous positive airway pressure for preventing morbidity and mortality in very preterm infants

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. 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. 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. 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. 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). 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.