We conducted a double-blind, randomized controlled trial to assess the efficacy of a combination of prophylactic systemic dexamethasone (SD) and nebulized budesonide (NB) in reducing the incidence and severity of chronic lung disease (CLD) in VLBW infants at risk. Fifty-nine ventilator-dependent infants < 30 wks and ≤ 1500 g were assigned to receive either steroids(S) or saline placebo as of 7 d of age. The S group (n=30, GA=25.8±1.6 wks, BW=731±144 g) received SD 0.25 mg/kg twice daily for 3 days, followed by NB 500 μg twice daily for 18 days. Control infants (n=29, GA=25.9±1.8 wks, BW=796±199 g) received systemic and inhaled saline.

Survival to discharge was similar in the 2 groups (73.3% vs. 82.8% in controls). Infants on S required less ventilatory support between 9 and 17 d of age (p ≤ 0.01) and less supplemental O2 between 8 and 10 d of age(p < 0.05), and had better pulmonary compliance at 10 d of age (p = 0.01). However, these differences were not maintained over the ensuing weeks. Elastase/albumin ratios in the tracheal effluents were similar in the 2 groups during the first month of life. Fewer S infants required late rescue therapy with SD (23.3% vs. 55.2% in controls, p = 0.017). There were no significant differences in timing of extubation (median 39.8 d vs. 38.5 d in controls), and of discontinuation of supplemental O2 in survivors (64.3 ± 33.3 d vs. 74.7 ± 43.3 d in controls). The incidence of CLD at 36 weeks in survivors was 45.5% vs. 54.2% in controls (p=0.77), and length of hospital stay was similar. No steroid-related adverse effects were noted in the S group, other than transient glycosuria. Serial serum cortisol and plasma ACTH values during the treatment period were similar in the 2 groups.

We conclude that early use of SD is associated with improvement in pulmonary function, which is not maintained once the infants are switched to NB. However, the combination of a short course of SD followed by NB reduces the need for subsequent SD exposure in VLBW infants with CLD. It remains to be clarified whether much earlier and exclusive administration of systemic steroids, or improved delivery of inhaled steroids is the best future strategy in the prevention of CLD.