Background: Respiratory distress syndrome (RDS) is caused by a deficiency or dysfunction of pulmonary surfactant. A wide variety of surfactant products have been formulated and studied in clinical trials. These include synthetic surfactants and animal derived surfactant extracts. Trials of surfactant replacement have either tried to prevent the development of respiratory distress in high-risk premature infants or treat established respiratory distress in premature infants.
Objectives: To assess the effect of administration of animal derived surfactant extract on mortality, chronic lung disease and other morbidities associated with prematurity in preterm infants with established respiratory distress syndrome. Subgroup analysis were planned according to the specific surfactant product, the degree of prematurity, and the severity of disease.
Search strategy: Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, and CINAHL from 1975 through December 2008. In addition, searches were made of previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants and journal hand searching in the English language.
Selection criteria: Randomized or quazi-randomized controlled trials that compared the effect of animal derived surfactant extract treatment administered to infants with established respiratory distress syndrome in order to prevent complications of prematurity and mortality.
Data collection and analysis: Data regarding clinical outcomes were excerpted from the reports of the clinical trials by the review authors. Data analysis was done in accordance with the standards of the Cochrane Neonatal Review Group.
Main results: Thirteen randomized controlled trials were included in the analysis. The studies demonstrated an initial improvement in respiratory status (improved oxygenation and decreased need for ventilator support). The meta-analysis supports a significant decrease in the risk of any air leak (typical relative risk 0.47, 95% CI 0.39, 0.58; typical risk difference -0.16, 95% CI -0.21, -0.12), pneumothorax (typical relative risk 0.42, 95% CI 0.34, 0.52; typical risk difference -0.17, 95% CI -0.21, -0.13), and a significant decrease in the risk of pulmonary interstitial emphysema (typical relative risk 0.45, 95% CI 0.37, 0.55; typical risk difference -0.20, 95% CI -0.25, -0.15). There is a significant decrease in the risk of neonatal mortality (typical relative risk 0.68, 95% CI 0.57, 0.82; typical risk difference -0.09, 95% CI -0.13, -0.05), a significant decrease in the risk of mortality prior to hospital discharge (typical relative risk 0.63, 95% CI 0.44, 0.90; typical risk difference -0.10, 95% CI -0.18, -0.03) and a significant decrease in the risk of bronchopulmonary dysplasia (BPD) or death at 28 days of age (typical relative risk 0.83, 95% CI 0.77, 0.90; typical risk difference -0.11, 95 CI -0.16, -0.06). No differences are reported in the risk of patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage, BPD or retinopathy of prematurity.
Authors' conclusions: Infants with established respiratory distress syndrome who receive animal derived surfactant extract treatment have a decreased risk of pneumothorax, a decreased risk of pulmonary interstitial emphysema, a decreased risk of mortality, and a decreased risk of bronchopulmonary dysplasia or death.