Natural surfactant extract versus synthetic surfactant for neonatal respiratory distress syndrome

Cochrane Database Syst Rev. 2001;(2):CD000144. doi: 10.1002/14651858.CD000144.


Background: Surfactant preparations are now widely used and have been credited with recent improvements in overall infant mortality (Horbar 1993b, Schwartz 1994). A wide variety of surfactant preparations have been developed and tested. These include synthetic surfactants and surfactants derived from animal sources. Although clinical trials have demonstrated that both synthetic surfactants and natural surfactant preparations are effective, comparison in animal models has suggested that there may be greater efficacy of natural surfactant products, perhaps due to the protein content of natural surfactant (Tooley 1987).

Objectives: To compare the effect of synthetic surfactant to natural surfactant in premature infants at risk for or having respiratory distress syndrome.

Search strategy: Searches were made of the Oxford Database of Perinatal Trials, Medline 1975 through December 2000 (MeSH terms: pulmonary surfactant; limits: age groups, newborn infant; publication type, clinical trial), previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants, and journal hand searching in the English language.

Selection criteria: Randomized controlled trials comparing administration of synthetic surfactants to administration of natural surfactant extracts in premature infants at risk for or having respiratory distress syndrome were considered for this review.

Data collection and analysis: Data regarding clinical outcomes including pneumothorax, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage (all intraventricular hemorrhage and severe intraventricular hemorrhage), bronchopulmonary dysplasia, chronic lung disease, retinopathy of prematurity, and mortality were excerpted by both reviewers. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group.

Main results: Eleven trials met inclusion criteria. The meta-analysis shows that the use of natural surfactant rather than synthetic surfactant results in a significant reduction in the risk of pneumothorax (typical relative risk 0.63, 95% CI 0.53, 0.75; typical risk difference -0.04, 95% CI -0.06, -0.03) and the risk of mortality (typical relative risk 0.87, 95% CI 0.76, 0.98; typical risk difference -0.02, 95% CI -0.05, 0.00). Natural surfactant extract is associated with a marginal increase in the risk of intraventricular hemorrhage (typical relative risk 1.09, 95% CI 1.00, 1.19; typical risk difference 0.03, 95% CI 0.00, 0.06), but no increase in grade 3 to 4 intraventricular hemorrhage (typical relative risk 1.08, 95% CI 0.92, 1.28; typical risk difference 0.01, 95% CI -0.01, 0.03). The meta-analyses support a marginal decrease in the risk of bronchopulmonary dysplasia or mortality associated with the use of natural surfactant preparations (typical relative risk 0.95, 95% CI 0.90, 1.01; typical risk difference -0.03, 95% CI -0.06, 0.00). No other relevant differences in outcome are noted.

Reviewer's conclusions: Both natural surfactant extracts and synthetic surfactant extracts are effective in the treatment and prevention of respiratory distress syndrome. Comparative trials demonstrate greater early improvement in the requirement for ventilator support, fewer pneumothoraces, and fewer deaths associated with natural surfactant extract treatment. Natural surfactant may be associated with an increase in intraventricular hemorrhage, though the more serious hemorrhages (Grade 3 and 4) are not increased. Despite these concerns, natural surfactant extracts would seem to be the more desirable choice when compared to currently available synthetic surfactants.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Drug Combinations
  • Fatty Alcohols / therapeutic use
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Polyethylene Glycols / therapeutic use
  • Pulmonary Surfactants / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Respiratory Distress Syndrome, Newborn / drug therapy*


  • Drug Combinations
  • Fatty Alcohols
  • Pulmonary Surfactants
  • Polyethylene Glycols