University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site

Question

• MQ is a 1150 gram former 27 week premature infant with Respiratory Distress Syndrome requiring mechanical ventilation and supplemental oxygen at 10 days of age. Would inhaled steroids help prevent her disease from progressing to bronchopulmonary dysplasia (BPD)?

Clinical Bottom Lines

In premature infants at risk for bronchopulmonary dysplasia, inhaled beclomethasone:

1. Did NOT decrease the incidence of BPD at 28 days or 36 weeks corrected gestational age.
2. Decreased the need for systemic glucocorticoids at 28 days.
3. Decreased the need for mechanical ventilation at 28 days.
4. Showed a trend towards fewer days of supplemental oxygen and hospitalization.
5. Decreased the need for bronchodilator therapy through 36 weeks (1).
6. Is a treatment I would recommend for neonates at risk.

Summary of Key Evidence

1. Study: A multicenter, randomized, double-blind, placebo-controlled trial.
2. Subjects: Neonates 3 to 14 days old, with gestational age < 33 weeks and birthweight less than 1250 grams and need for mechanical ventilation.
3. Exclusion Criteria: Evidence of sepsis, glucose intolerance, hypertension, necrotizing enterocolitis, renal insufficiency, abnormal liver function, major congenital anomalies, or prior systemic glucocorticoid therapy.
4. Methods: Beclovent (beclomethasone dipropionate) and placebo metered dose inhalers were used with Aerochamber device delivered via endotracheal tube. The dose was decreased gradually over four weeks from 40 mcg/kg/day to 5 mcg/kg/day. Systemic glucocorticoids could be initiated at the discretion of the attending physician if the neonate had increasing oxygen requirements for at least 5 days and received the study drug at least 7 days.
5. Main Results: By 28 days or 36 weeks corrected gestational age in neonates who took inhaled beclomethasone, there was no difference in mortality or frequency of BPD, but fewer infants were receiving systemic glucocorticoids, and there was a 50% reduction in systemic steroid use after confounding factors were considered (gestational age, antenatal steroid use, or oxygenation index) (1).
6. Validity: This was a well designed study with many patients, and statistical analyses accounted for many potentially confounding variables. Yet a major confounder-the frequency of use of systemic glucocorticoids-was not accounted for in the ultimate results of the study. Because more of the placebo group received the systemic steroids, those patients were then less likely to be diagnosed with BPD.

Additional Comments

• The Cochrane data base combined data from 5 eligible studies, including Cole 1999. The meta-analysis showed similar results-no change in the incidence of BPD or mortality, but DID show a statistically significant reduction in the need for systemic glucocorticoids. To avoid the use of systemic glucocorticoids, the NNT was 10. However, the consensus was that inhaled steroids were not recommended as the standard of treatment because of the heterogeneity of data regarding the use of systemic steroids (2).
• The Cochrane database also showed that none of the individual trials or meta-analyses showed a difference in adverse outcome, including infection, hypertension, hyperglycemia, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, gastrointestinal bleeding, patent ductus arteriosus, or retinopathy of prematurity (2).
• Inhaled steroids are relatively inexpensive with few side effects, as compared to the cost savings of decreased time on the ventilator, and the theoretical decreased incidence of neuromotor side effects by avoiding systemic glucocorticoids.

Citation

1. Cole, Cynthia H et al. Early inhaled glucocorticoid therapy to prevent brochopulmonary dysplasia. The New England Journal of Medicine 1999; 340 (13):1005-1010.
2. Shah, V et al. Early administration of inhaled corticosteroids for preventing chronic lung disease in ventilated very low birth weight preterm neonates. The Cochrane Database of Systematic Reviews May 2000; Issue 3.

CAT Author: Cheryl Green, MD

CAT Appraisers: John G. Frohna, MD, MPH

Date appraised: December 4, 2000