Administration of budesonide to extreme preterm newborns to prevent severe chronic pulmonary disease does not induce long-term neurodevelopmental impairments, such as cerebral palsy, cognitive delay, hearing impairment, or blindness, according to the results of a Phase 3 trial.
The trial (NCT01035190) data were reported in an article titled “Long-Term Effects of Inhaled Budesonide for Bronchopulmonary Dysplasia,” published in The New England Journal of Medicine.
Bronchopulmonary dysplasia is a severe lung disease characterized by the destruction of lung air sacs. It is a common complication among extremely preterm babies, and is associated with a poorer prognosis. Infants who survive to this disease are more susceptible to develop respiratory and cardiovascular impairment, growth failure, and neurodevelopmental delay.
Glucocorticoid therapies, such as budesonide (marketed as Pulmicort, among other brand names), have been demonstrated to effectively prevent the development of bronchopulmonary dysplasia. However, they have also been associated with an increased risk of neurodevelopmental impairment. But little is known about the short- and long-term effects of these therapies in the development of infants.
The trial enrolled 863 infants, with a gestational age of 23 weeks to 27 weeks and 6 days, from across 40 clinical centers in 9 countries. All infants required respiratory support, and were randomly assigned to receive, within 24 hours after birth, inhaled budesonide or placebo.
The treated group received two puffs (200 μg per puff) every 12 hours during the first 14 days, followed by one puff every 12 hours for the remaining days until no respiratory support was needed or the infant reached the age of 32 weeks.
Researchers found that bronchopulmonary dysplasia at 36 weeks of postmenstrual age (gestational age plus chronological age) was less frequent in the budesonide-treated group than in the placebo group. The mortality rate, however, was found to be higher in the budesonide group compared to placebo.
Evaluation of the infant’s neurological development, which included a composite analysis of cognitive delay, cerebral palsy, hearing impairment, and blindness, showed no significant differences between the two groups. About 48.1% and 51.4% of the infants in the budesonide and placebo groups, respectively, had neurodevelopmental disability.
“There were no significant differences between the budesonide group and the placebo group with respect to the frequencies of the components of neurodevelopmental impairment,” the researchers wrote.
The research team concluded that inhaled budesonide did not change the risk of neurodevelopmental disability among surviving, extremely preterm infants at 2 years. “However, the mortality rate was higher in the budesonide group,” they added.