The administration of inhaled budesonide to extremely preterm infants did not increase the risk of neurodevelopmental disability, but did increase mortality, in a study by Dirk Bassler, MD, of the University of Zürich and his associates.

An older study led by Dr. Bassler and published in the New England Journal of Medicine showed that inhaled budesonide significantly reduced the incidence of bronchopulmonary dysplasia, which has been linked to higher mortality and chronic respiratory and cardiovascular impairment ( N Engl J Med. 2015;373:1497-506 ).

Systemic glucocorticoids have been linked to greater risk of neurodevelopmental disability, but only a few studies have examined the effect of inhaled glucocorticoids, such as budesonide, in preterm infants. These studies, including the earlier one by Dr. Bassler and his colleagues, were either small, covered a short period of time or involved late administering of the drug.

In the two studies by Dr. Bassler and his colleagues, 863 preterm infants between 23 weeks’ and just under 28 weeks’ gestation who required any form of positive-pressure respiratory support were randomized to receive inhaled budesonide (two puffs, 200 mcg per puff) or placebo every 12 hours. They began within 24 hours of birth and continued for the first 14 days of life. Following that, patients received 1 puff every 12 hours until they no longer required supplemental oxygen and positive-pressure support, or reached a postmenstrual age of 32 weeks.

The treatment resulted in a significant reduction in bronchopulmonary dysplasia at a postmenstrual age of 36 weeks (28.2% in the budesonide group vs. 37.4%; P = .01), in the older study.

In the new study , which was also published in the New England Journal of Medicine, Dr. Bassler and his associates found higher mortality (19.9% vs. 14.5%; relative risk, 1.37; 95% confidence interval, 1.01-1.86; P = .04) in the group of patients who had received inhaled budesonide. Additionally, at a corrected age of 18-22 months, surviving infants who received inhaled budesonide had a similar risk of neurodevelopmental disability as those patients who took the placebo.

Broadly speaking, 48.1% of infants who received budesonide had a neurodevelopmental disability, compared with 51.4% of infants who received placebo (RR adjusted for gestational age, 0.93; 95% CI, 0.80-1.09; P = .40). The two groups also had no statistically significant differences in their frequencies of cerebral palsy, blindness, hearing loss, or cognitive delay.

“There was no significant difference between the groups in adverse long-term outcomes in our study. However, the fact that fewer infants died in the placebo group than in the budesonide group complicates the interpretation of the treatment of budesonide,” the researchers wrote.

Supported by a grant from the European Union and by Chiesi Farmaceutici. Disclosure forms provided by the authors are available with the full text of this article at .

SOURCE: N Engl J Med. 2018;378:148-57 .


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