Early administration of inhaled corticosteroids for preventing chronic lung disease in ventilated very low birth weight preterm neonates

Cochrane Database Syst Rev. 2012 May 16:(5):CD001969. doi: 10.1002/14651858.CD001969.pub3.


Background: Chronic lung disease remains a common complication among preterm infants. There is increasing evidence that inflammation plays an important role in the pathogenesis of CLD. Due to their strong anti-inflammatory properties, corticosteroids are an attractive intervention strategy. However, there are growing concerns regarding short and long-term effects of systemic corticosteroids. Theoretically, administration of inhaled corticosteroids may allow for beneficial effects on the pulmonary system with a lower risk of undesirable systemic side effects.

Objectives: To determine the impact of inhaled corticosteroids administered to ventilated very low birth weight preterm neonates in the first two weeks of life for the prevention of chronic lung disease (CLD).

Search methods: Randomised and quasi-randomised trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2007), MEDLINE (1966 to July 2007), EMBASE (1980 to July 2007), CINAHL (1982 to July 2007), reference lists of published trials and abstracts published in Pediatric Research or electronically on the Pediatric Academic Societies web-site (1990 to April 2007).This search was updated in 2011.

Selection criteria: Randomised controlled trials of inhaled corticosteroid therapy initiated within the first two weeks of life in ventilated preterm infants with birth weight <1500 grams were included in this review.

Data collection and analysis: Data regarding clinical outcomes including chronic lung disease at 28 days or 36 weeks postmenstrual age (PMA), mortality, combined outcome of death or CLD at 28 days of age and at 36 weeks PMA, the need for systemic corticosteroids, failure to extubate within 14 days and adverse effects of corticosteroids were evaluated. All data were analysed using RevMan 4.2.10. When possible, meta-analysis was performed using relative risk (RR), risk difference (RD), along with their 95% confidence intervals (CI). If RD was significant, the number needed to treat (NNT) was calculated.

Main results: One ongoing trial was identified for inclusion in this update. Eleven trials assessing the impact of inhaled corticosteroid for the prevention of CLD were identified. Four trials were excluded. The present review includes data analyses based on seven qualifying trials. There was no statistically significant effect of inhaled steroids on CLD either at 28 days [typical RR 1.05 (95% CI 0.84 to 1.32); typical RD 0.02 (95% CO -0.07 to 0.11)] or at 36 weeks PMA [typical RR 0.97 (95% CI 0.62 to 1.52); typical RD 0.00 (95% CI -0.07, 0.06)], when analysed either for all randomised infants or among survivors. No statistically significant differences were noted for mortality or for the combined outcome of mortality and CLD either at 28 days of age or at 36 weeks PMA. There were no statistically significant differences in adverse events between groups.

Authors' conclusions: Based on this updated review, there is no evidence from the trials reviewed that early administration (in the first two weeks of life) of inhaled steroids to ventilated preterm neonates was effective in reducing the incidence of CLD. Currently, use of inhaled steroids in this population cannot be recommended. Studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for the administration of these medications. Studies need to address both the short-term and long-term benefits and adverse effects of inhaled steroids with particular attention to neurodevelopmental outcome.

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / therapeutic use*
  • Chronic Disease
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / therapeutic use*
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / mortality
  • Infant, Premature, Diseases / prevention & control*
  • Infant, Very Low Birth Weight
  • Lung Diseases / mortality
  • Lung Diseases / prevention & control*
  • Randomized Controlled Trials as Topic
  • Respiration, Artificial*
  • Steroids / administration & dosage
  • Time Factors


  • Anti-Inflammatory Agents
  • Glucocorticoids
  • Steroids