SYSTEMATIC REVIEW
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Early versus delayed selective surfactant treatment for neonatal respiratory distress syndrome.

BACKGROUND: This section is under preparation and will be included in the next issue.

OBJECTIVES: To compare the effects of early vs. delayed selective surfactant therapy for newborns intubated for respiratory distress within the first two hours of life. Planned subgroup analyses include separate comparisons for studies utilizing natural surfactant extract and synthetic surfactant.

SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal Trials, Medline (MeSH terms: pulmonary surfactant; text word: early; limits: age, newborn: publication type, clinical trial), PubMed, abstracts, conference and symposia proceedings, expert informants, and journal hand searching in the English language.

SELECTION CRITERIA: Only randomized controlled clinical trials comparing early selective surfactant administration (surfactant administration via the endotracheal tube in infants intubated for respiratory distress, not specifically for surfactant dosage) within the first 2 hours of life versus delayed selective surfactant administration to infants with established respiratory distress syndrome were considered for review.

DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including the incidence of pneumothorax, patent ductus arteriosus, pulmonary interstitial emphysema, pulmonary hemorrhage, necrotizing enterocolitis, retinopathy of prematurity, intraventricular hemorrhage (any and severe IVH), bronchopulmonary dysplasia, chronic lung disease, neonatal mortality, mortality prior to hospital discharge, bronchopulmonary dysplasia or death, and chronic lung disease or death were excerpted from the reports of the clinical trials by the reviewers. Data regarding the average number of surfactant doses per infant were also analyzed. Further analysis of data with regard to surfactant type was performed. Data analysis was performed in accordance with the standards of the Cochrane Neonatal Review Group.

MAIN RESULTS: Four randomized controlled trials met selection criteria. Two of the trials utilized synthetic surfactant (Exosurf Neonatal) and two utilized a natural surfactant extract. The meta-analyses demonstrated significant reductions in risk of pneumothorax (Typical RR 0.70, 95%CI 0.59, 0.82; Typical RD -0.05, 95%CI -0.08, -0.03), and pulmonary interstitial emphysema (Typical RR 0.63, 95%CI 0.43, 0.93; Typical RD -0.06, 95%CI -0.10, -0.01) in infants randomized to early selective surfactant administration. Infants randomized to early selective surfactant administration also demonstrated a decreased risk of neonatal mortality (Typical RR 0.87, 95%CI 0.77, 0.99; Typical RD -0.03, 95%CI -0.06, -0.00), chronic lung disease (Typical RR 0.70, 95%CI 0. 55, 0.88; Typical RD -0.03, 95%CI -0.05, -0.01), and chronic lung disease or death at 36 weeks (Typical RR 0.84, 95%CI 0.75, 0.93; Typical RD -0.06, 95%CI -0.09, -0.03). A trend toward risk reduction for bronchopulmonary dysplasia or death at 28 days was also evident (Typical RR 0.94, 95%CI 0.88, 1.00; Typical RD -0.04, 95%CI -0.07, -0.00). No differences in other complications of RDS or prematurity were noted.

REVIEWER'S CONCLUSIONS: Early selective surfactant administration given to infants with RDS requiring assisted ventilation leads to a decreased risk of acute pulmonary injury (decreased risk of pneumothorax and pulmonary interstitial emphysema) and a decreased risk of neonatal mortality and chronic lung disease compared to delaying treatment of such infants until they develop established RDS.

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