Surfactant Nebulization to Prevent Intubation in Preterm Infants: A Systematic Review and Meta-analysis

CONTEXT: Surfactant nebulization (SN) may offer a safe alternative for surfactant administration in respiratory distress syndrome of preterm infants. OBJECTIVE: To evaluate the efficacy of SN for the prevention of early intubation. DATA SOURCES: Medline, Embase, The Cochrane Library, clinicaltrials.gov, published abstracts, and references of relevant articles were searched through March 23, 2021. STUDY SELECTION: Randomized clinical trials of preterm infants <37 weeks' gestation comparing SN with noninvasive respiratory support or intratracheal surfactant application. DATA EXTRACTION: Two reviewers extracted data and assessed risk of bias from included studies separately and blinded. Data were pooled by using a fixed-effects model. Subgroups (gestational age, type of nebulizer, surfactant type, and dosage) were evaluated. Primary outcome was intubation rate at 72 hours after birth. RESULTS: Nine studies recruiting 1095 infants met inclusion criteria. SN compared with standard care significantly reduced intubation rate at 72 hours after birth (226 of 565 infants [40.0%] vs 231 of 434 infants [53.2%]; risk ratio [RR]: 0.73, 95% confidence interval [CI]: 0.63-0.84; number needed to treat: 8; 95% CI: 5-14]). Prespecified subgroup analysis identified important heterogeneity: SN was most effective in infants $28 weeks' gestation (RR: 0.70, 95% CI: 0.60-0.82), with a pneumatically driven nebulizer (RR: 0.52, 95% CI: 0.40-0.68) and in infants receiving >= 200 mg/kg and animal-derived surfactant (RR: 0.63, 95% CI: 0.52-0.75). No differences in neonatal morbidities or mortality were identified. LIMITATIONS: Quality of evidence was low owing to risk of bias and imprecision. CONCLUSIONS: SN reduced the intubation rate in preterm infants with a higher efficacy for specific subgroups. There was no difference in relevant neonatal morbidities or mortality.