Inhaled versus systemic corticosteroids for the treatment of chronic lung disease in ventilated very low birth weight preterm infants

BACKGROUND: Chronic lung disease (CLD) remains a serious and common problem among very low birth weight (VLBW) infants despite the use of antenatal steroids and postnatal surfactant therapy to decrease the incidence and severity of respiratory distress syndrome. Due to their anti-inflammatory properties, corticosteroids have been widely used to treat or prevent CLD. However, the use of systemic steroids has been associated with serious short and long-term adverse effects. Administration of corticosteroids topically through the respiratory tract might result in beneficial effects on the pulmonary system with fewer undesirable systemic side effects. OBJECTIVES: To determine the effect of inhaled versus systemic corticosteroids administered to ventilator dependent preterm neonates with birth weight < 1500 g or gestational age < 32 weeks after two weeks of life for the treatment of evolving 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 June 2007), EMBASE (1980 to June 2007), CINAHL (1982 to June 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 June 2011 and included additional searches of Clinicaltrials.gov, Controlled-trials.com and Web of Science. SELECTION CRITERIA: Randomised or quasi-randomised trials comparing inhaled versus systemic corticosteroid therapy (irrespective of the dose and duration of therapy) starting after the first two weeks of life in ventilator dependent VLBW infants. DATA COLLECTION AND ANALYSIS: Data were extracted regarding clinical outcomes and were analysed using Review Manager. When appropriate, meta-analysis was performed using relative risk (RR), risk difference (RD), and weighted mean difference (WMD) along with their 95% confidence intervals (CI). If RD was statistically significant, the number needed to benefit (NNTB) or the number needed to harm (NNTH) was calculated. MAIN RESULTS: Five trials comparing inhaled versus systemic corticosteroids in the treatment of CLD were identified. Two trials were excluded as both included non-ventilator dependent patients and three trials qualified for inclusion in this review. No new trials were identified in the 2011 update.Halliday et al (Halliday 2001) randomised infants at < 72 hours (n = 292), while Rozycki et al (Rozycki 2003) and Suchomski et al (Suchomski 2002) randomised at 12 to 21 days. The data from the two trials of Rozycki et al and Suchmoski et al are combined using meta-analytic techniques. The data from the trial by Halliday et al are reported separately, as outcomes were measured over different time periods from the age at randomisation.In none of the trials was there a statistically significant difference between the groups in the incidence of CLD at 36 weeks PMA among all randomised infants. The estimates for the trial by Halliday et al (Halliday 2001) were RR 1.10 (95% CI 0.82 to 1.47), RD 0.03 (95% CI -0.08 to 0.15).For the trials by Rozycki et al (Rozycki 2003) and Suchomski et al (Suchomski 2002) the typical RR was 1.02 (95% CI 0.83 to 1.25) and the typical RD 0.01 (95% CI -0.11 to 0.14); (number of infants = 139 ). There were no statistically significant differences between the groups in either trial for oxygen dependency at 28 days of age, death by 28 days or 36 weeks PMA, the combined outcome of death by or CLD at 28 days or 36 weeks PMA, duration of intubation, duration of oxygen dependence, or adverse effects. Information on the long-term neurodevelopmental outcomes was not available. AUTHORS' CONCLUSIONS: This review found no evidence that inhaled corticosteroids confer net advantages over systemic corticosteroids in the management of ventilator dependent preterm infants. Neither inhaled steroids nor systemic steroids can be recommended as standard treatment for ventilated preterm infants. There was no evidence of difference in effectiveness or side-effect profiles for inhaled versus systemic steroids. A better delivery system guaranteeing selective delivery of inhaled steroids to the alveoli might result in beneficial clinical effects without increasing side-effects. To resolve this issue, studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for the administration of these medications. The long-term effects of inhaled steroids, with particular attention to neurodevelopmental outcome, should be addressed in future studies.

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