Comparison of animal-derived surfactants for the prevention and treatment of respiratory distress syndrome in preterm infants

Review question: Does the use of one animal-derived surfactant preparation compared with an alternative animal-derived surfactant preparation lead to improved outcome in infants at risk for or having respiratory distress syndrome?

Background: A wide variety of surfactant preparations are used to prevent or treat respiratory distress syndrome (RDS) in preterm infants. All commercially available animal-derived surfactant products are effective for prevention and treatment of respiratory distress syndrome in preterm infants. However, it is unclear whether significant differences in clinical outcome exist among the available animal-derived surfactant extracts. This review compared different animal-derived surfactant products based on their source (bovine vs. porcine) and method of extraction (minced lung vs. lung lavage).

Study characteristics: 16 randomized controlled trials met our inclusion criteria.

Results: We found improvement in risk of death before hospital discharge and the risk of combined outcome of death or oxygen requirement at four weeks before due date of birth with the use of higher dose of porcine surfactant (a surfactant product derived from pig's lung) compared with a minced bovine surfactant (surfactant obtained from minced cow's lung). Based on the available evidence, we cannot state with certainty whether the improvement in outcome with high dose porcine-derived surfactant is from dose effect (higher phospholipid levels with use of higher initial dose) or from the effect of source of surfactant extraction (pig vs. cow). Comparison trials of surfactants obtained from bovine sources that used different extraction methods or modifications showed no difference in clinical outcomes.

Authors' conclusions: 

Significant differences in clinical outcome were noted in the comparison trials of modified minced lung surfactant extract (beractant) compared with porcine minced lung surfactant extract (poractant alfa) including a significant increase in the risk of mortality prior to discharge, death or oxygen requirement at 36 weeks' postmenstrual age, PDA requiring treatment and "receiving > 1 dose of surfactant" in infants treated with modified bovine minced lung surfactant extract compared with porcine minced lung surfactant extract. The difference in these outcomes was limited to studies using a higher initial dose of porcine minced lung surfactant extract. It is uncertain whether the observed differences are from differences in dose or from source of extraction (porcine vs. bovine) because of the lack of dose-equivalent comparison groups with appropriate sample size. No differences in clinical outcomes were observed in comparative trials between bovine lung lavage surfactant and modified bovine minced lung surfactants.

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Background: 

Animal-derived surfactants have been shown to have several advantages over the first generation synthetic surfactants and are the most commonly used surfactant preparations. The animal-derived surfactants in clinical use are minced or lavaged and modified or purified from bovine or porcine lungs. It is unclear whether significant differences in clinical outcome exist among the available bovine (modified minced or lavage) and porcine (minced or lavage) surfactant extracts.

Objectives: 

To compare the effect of administration of different animal-derived surfactant extracts on the risk of mortality, chronic lung disease, and other morbidities associated with prematurity in preterm infants at risk for or having respiratory distress syndrome (RDS).

Search strategy: 

We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), MEDLINE via PubMed (1966 to July 31, 2015), EMBASE (1980 to July 31, 2015), and CINAHL (1982 to July 31, 2015). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials.

Selection criteria: 

Randomized or quasi-randomized controlled trials that compared the effect of animal-derived surfactant extract treatment administered to preterm infants at risk for or having RDS 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. Subgroup analyses were performed based on gestational age, surfactant dosing and schedule, treatment severity and treatment strategy. Data analysis was performed in accordance with the standards of the Cochrane Neonatal Review Group.

Main results: 

Sixteen randomized controlled trials were included in the analysis.

Bovine lung lavage surfactant extract to modified bovine minced lung surfactant extract: Seven treatment studies and two prevention studies compared bovine lung lavage surfactant extract to modified bovine minced lung surfactant extract. The meta-analysis did not demonstrate any significant differences in death or chronic lung disease in the prevention trials (typical RR 1.02, 95% CI 0.89 to 1.17; typical RD 0.01, 95% CI −0.05 to 0.06; 2 studies and 1123 infants; high quality evidence) or treatment trials (typical RR 0.95, 95% CI 0.86 to 1.06; typical RD −0.02 , 95% CI −0.06 to 0.02; 3 studies and 2009 infants; high quality evidence)

Modified bovine minced lung surfactant extract compared with porcine minced lung surfactant extract: Nine treatment studies compared modified bovine minced lung surfactant extract to porcine minced lung surfactant extract. Meta-analysis of these trials demonstrate a significant increase in the risk of mortality prior to hospital discharge (typical RR 1.44, 95% CI 1.04 to 2.00; typical RD 0.05, 95% CI 0.01 to 0.10; NNTH 20, 95% CI 10 to 100; 9 studies and 901 infants; moderate quality evidence), death or oxygen requirement at 36 weeks' postmenstrual age (typical RR 1.30, 95% CI 1.04 to 1.64; typical RD 0.11, 95% CI 0.02 to 0.20; NNTH 9, 95% CI 5 to 50; 3 studies and 448 infants; moderate quality evidence), receiving more than one dose of surfactant (typical RR 1.57, 95% CI 1.29 to 1.92; typical RD 0.14, 95% CI 0.08 to 0.20; NNTH 7, 95% CI 5 to 13; 6 studies and 786 infants), and patent ductus arteriosus (PDA) requiring treatment (typical RR 1.86, 95% CI 1.28 to 2.70; typical RD 0.28, 95% CI 0.13 to 0.43; NNTH 4, 95% CI 2 to 8; 3 studies and 137 infants) in infants treated with modified bovine minced lung surfactant extract compared with porcine minced lung surfactant extract. In the subgroup analysis based on initial dose of surfactant, improvement in mortality prior to discharge (typical RR 1.62, 95% CI 1.11 to 2.38; typical RD 0.06, 95% CI 0.01 to 0.11; NNTH 16, 95% CI 9 to 100) and risk of death or oxygen requirement at 36 weeks' postmenstrual age (typical RR 1.39, 95% CI 1.08 to 1.79; typical RD 0.13, 95% 0.03 to 0.23; NNTH 7, 95% CI 4 to 33) was limited to higher initial dose of porcine minced lung surfactant (> 100 mg/kg).

Other comparisons: No difference in outcome was noted between bovine lung lavage surfactant extract versus porcine minced lung surfactant extract. There were no studies comparing bovine lung lavage surfactant extract versus porcine lung lavage surfactant; or porcine minced lung surfactant extract versus porcine lung lavage surfactant.

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