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

Pediatrics. 2021 Nov;148(5):e2021052504. doi: 10.1542/peds.2021-052504. Epub 2021 Oct 28.


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,, 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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Administration, Inhalation
  • Confidence Intervals
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Intubation, Intratracheal / statistics & numerical data*
  • Nebulizers and Vaporizers
  • Pulmonary Surfactants / administration & dosage*
  • Randomized Controlled Trials as Topic
  • Respiratory Distress Syndrome, Newborn / drug therapy*
  • Time Factors


  • Pulmonary Surfactants