Infants treated with budesonide within the first 24 hours of life may experience a lower rate of bronchopulmonary dysplasia, with no differences in long-term adverse outcomes or rate of neurodevelopmental disability compared with placebo, according to a study published in the New England Journal of Medicine.
Researchers identified 863 infants born at 36 weeks postmenstrual during a 3-year period at 40 trial centers in 9 different countries and randomly assigned them to receive either inhaled budesonide (n=437) or placebo (n=419) within 24 hours of birth. The primary outcome of this randomized placebo-controlled trial was to observe the short and long-term efficacy and safety of inhaled budesonide in preterm infants within 24 hours of birth for the prevention of bronchopulmonary dysplasia (ClinicalTrials.gov identifier: NCT01035190). In addition, the rate of neurodevelopmental disability (cerebral palsy, cognitive delay, deafness, or blindness) was altered at the corrected age of 18 to22 months after receiving budesonide to prevent bronchopulmonary dysplasia.
Study results demonstrated a nonsignificant difference between infants who received budesonide compared with infants who received placebo (P =.05). However, mortality was slightly higher in infants treated with budesonide (59%) than in infants treated with placebo (58.8%; relative risk [RR], 1.00; 95% CI, 0.89-1.13; P =.97). Therefore, an external safety monitoring committee recommended that the trial drugs be discontinued. Of note, the rate of bronchopulmonary dysplasia at 36 weeks was found to be lower in infants treated in the budesonide group compared with placebo.
In the 308 infants assigned to receive budesonide and 321 assigned to receive the placebo, neurodevelopmental disabilities were found in 148 and 165 infants, respectively (RR, adjusted for gestational age, 0.93; 95% CI, 0.80-1.09; P =.40)
Investigators concluded that there were no significant differences in the frequency of the components of neurodevelopmental impairment at 2 years (cognitive delay, cerebral palsy, hearing impairment, and blindness) or composite outcome of death in preterm infants in whom inhaled budesonide or placebo was initiated within 24 hours of birth to prevent the development of bronchopulmonary dysplasia.
Although long-term outcomes did not differ significantly in the two groups, clinicians should be cautious when using budesonide in this patient population because of the slightly higher mortality rate compared with placebo.
Bassler D, Shinwell ES, Hallman M, et al. Long-term effects of inhaled budesonide for bronchopulmonary dysplasia. N Engl J Med. 2018;378:148-157.