PEDIATRICS Vol. 107 No. 2 February 2001, pp. 232-240
A Multicenter, Randomized Open Study of Early Corticosteroid Treatment (OSECT) in Preterm Infants With Respiratory Illness: Comparison of Early and Late Treatment and of Dexamethasone and Inhaled Budesonide
Received May 1, 2000; accepted Jul 31, 2000.
,
From the Regional Neonatal Unit, Royal Maternity Hospital and
Departments of * Child Health and Epidemiology and Public Health, The
Queen's University of Belfast, Belfast, Northern Ireland.
Aim. To compare early (<3 days) with late (>15 days) steroid therapy and dexamethasone with inhaled budesonide in very preterm infants at risk of developing chronic lung disease.
Methods. Five hundred seventy infants from 47 neonatal intensive care units were enrolled. Criteria for enrollment included gestational age <30 weeks, postnatal age <72 hours, and need for mechanical ventilation and inspired oxygen concentration >30%. Infants were randomly allocated to 1 of 4 treatment groups in a factorial design: early (<72 hours) dexamethasone, early budesonide, delayed selective (>15 days) dexamethasone, and delayed selective budesonide. Dexamethasone was given in a tapering course beginning with 0.50 mg/kg/day in 2 divided doses for 3 days reducing by half until 12 days of therapy had elapsed. Budesonide was administered by metered dose inhaler and a spacing chamber in a dose of 400 µg/kg twice daily for 12 days. Delayed selective treatment was started if infants needed mechanical ventilation and >30% oxygen for >15 days. The factorial design allowed 2 major comparisons: early versus late treatment and systemic dexamethasone versus inhaled budesonide. The primary outcome was death or oxygen dependency at 36 weeks and analysis was on an intention-to-treat basis. Secondary outcome measures included death or major cerebral abnormality, duration of oxygen treatment, and complications of prematurity. Adverse effects were also monitored daily.
Results. There were no significant differences among the groups for the primary outcome. Early steroid treatment was associated with a lower primary outcome rate (odds ratio [OR]: 0.85; 95% confidence interval [CI]: 0.61,1.18) but even after adjustment for confounding variables the difference remained nonsignificant. Dexamethasone-treated infants also had a lower primary outcome rate (OR: 0.86; 95% CI: 0.62,1.20) but again this difference remained not significant after adjustment. For death before discharge, dexamethasone and early treatment had worse outcomes than budesonide and delayed selective treatment (OR: 1.42; 95% CI: 0.93,2.16; OR: 1.51; 95% CI: 0.99,2.30 after adjustment, respectively) with the results not quite reaching significance. Duration of supplementary oxygen was shorter in the early dexamethasone group (median: 31 days vs 40-44 days). Early dexamethasone was also associated with increased weight loss during the first 12 days of treatment (52 g vs 3 g) compared with early budesonide, but over 30 days there was no difference. In the early dexamethasone group, there was a reduced incidence of persistent ductus arteriosus (34% vs 52%-59%) and an increased risk of hyperglycemia (55% vs 29%-34%) compared with the other 3 groups. Dexamethasone was associated with an increased risk of hypertension and gastrointestinal problems compared with budesonide but only the former attained significance.
Conclusions. Infants given early treatment and dexamethasone therapy had improved survival without chronic lung disease at 36 weeks compared with those given delayed selective treatment and inhaled budesonide, respectively, but results for survival to discharge were in the opposite direction; however, none of these findings attained statistical significance. Early dexamethasone treatment reduced the risk of persistent ductus arteriosus. Inhaled budesonide may be safer than dexamethasone, but there is no clear evidence that it is more or less effective. Key words: preterm, neonate, chronic lung disease, glucocorticoids, systemic dexamethasone, inhaled budesonide, spacing chamber, randomized clinical trial, bronchopulmonary dysplasia.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Basu, A. Kumar, B. D. Bhatia, K. Satya, and T. B. Singh Role of Steroids on the Clinical Course and Outcome of Meconium Aspiration Syndrome A Randomized Controlled Trial J Trop Pediatr, October 1, 2007; 53(5): 331 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Hartnett, D. J. Martiniuk, Y. Saito, P. Geisen, L. J. Peterson, and J. R. McColm Triamcinolone Reduces Neovascularization, Capillary Density and IGF-1 Receptor Phosphorylation in a Model of Oxygen-Induced Retinopathy Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 4975 - 4982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. T. Wilson, L. Waters, C. C. Patterson, C. G. McCusker, N. M. Rooney, N. Marlow, and H. L. Halliday Neurodevelopmental and Respiratory Follow-up Results at 7 Years for Children From the United Kingdom and Ireland Enrolled in a Randomized Trial of Early and Late Postnatal Corticosteroid Treatment, Systemic and Inhaled (the Open Study of Early Corticosteroid Treatment). Pediatrics, June 1, 2006; 117(6): 2196 - 2205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. K. Jones and on behalf of the Collaborative Dexamethasone Trial Randomized, Controlled Trial of Dexamethasone in Neonatal Chronic Lung Disease: 13- to 17-Year Follow-up Study: I. Neurologic, Psychological, and Educational Outcomes Pediatrics, August 1, 2005; 116(2): 370 - 378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. K. Jones and on behalf of the Collaborative Dexamethasone Trial Randomized, Controlled Trial of Dexamethasone in Neonatal Chronic Lung Disease: 13- to 17-Year Follow-up Study: II. Respiratory Status, Growth, and Blood Pressure Pediatrics, August 1, 2005; 116(2): 379 - 384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A. Parikh, R. G. Locke, A. Chidekel, K. H. Leef, J. Emberger, D. A. Paul, and J. L. Stefano Effect of Inhaled Corticosteroids on Markers of Pulmonary Inflammation and Lung Maturation in Preterm Infants With Evolving Chronic Lung Disease J Am Osteopath Assoc, March 1, 2004; 104(3): 114 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. A. McAlister, S. E. Straus, D. L. Sackett, and D. G. Altman Analysis and Reporting of Factorial Trials: A Systematic Review JAMA, May 21, 2003; 289(19): 2545 - 2553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Other Articles Noted Evid. Based Nurs., October 1, 2001; 4(4): E1 - 11. [Full Text] [PDF]
|
|
