Hydrocortisone was not superior to placebo in reducing the incidence of bronchopulmonary dysplasia in extremely preterm infants with bronchopulmonary dysplasia, according to a study from the United States recently reported in the New England Journal of Medicine.¹

The multicenter, randomized-controlled trial involved 800 preterm infants, <30 weeks gestational age (mean nearly 25 weeks), who were on ventilator support for a minimum period of one week at 14 to 28 days after birth. They were randomized to treatment with either hydrocortisone or placebo for 10 days, besides standard care and ventilator therapy. Hydrocortisone was given in a dose of 4 mg/kg/day, which was tapered to 0.5 mg/kg over the duration of administration. Infants who had received indomethacin or ibuprofen 48 hours before recruitment in the trial or had previous steroid treatment or those with major congenital abnormalities were not included in the trial.

Results showed that out of the 398 infants who received hydrocortisone, 66 (16.6%) survived at 36 weeks without moderate or severe bronchopulmonary dysplasia, which was the primary efficacy outcome. In the placebo-treated group, this number was 53 out of 402 (13.2%) infants, a difference that was not statistically different. At 2 years, no moderate or severe neurodevelopmental impairment, primary safety outcome, was evident in nearly 37% hydrocortisone-treated infants vs 37.3% in placebo-treated infants again showing no significant difference in the survival rates between the two groups. Extubation rate was nearly 45% in the hydrocortisone group vs 34% in the placebo group.

Hypertension occurred more often in the infants who received hydrocortisone compared to the placebo group and the antihypertensive treatment requirement was 4.3% vs 1.0%, respectively. No other differences in adverse events were noted between the two groups.

Bronchopulmonary dysplasia occurs commonly among very preterm newborns. While most recover, some may have persistent breathing difficulties. Steroids are often used in the management in addition to other drugs like diuretics, bronchodilators and oxygen for lack of a specific treatment. This study which aimed to examine the impact of hydrocortisone treatment on survival in preterm infants with bronchopulmonary dysplasia did not find any advantage over placebo in enhancing survival. The authors suggest that the lack of efficacy may have been due to the late timing of administration, when lung damage due to inflammation had already occurred. Many patients in the intervention as well as the placebo group had also received dexamethasone, which according to the authors was a limitation of their study. This suggests that a multipronged approach to treatment is required rather than a single intervention.

Reference

1. Watterberg KL, et al. Hydrocortisone to improve survival without bronchopulmonary dysplasia. N Engl J Med. 2022 Mar 24;386(12):1121-1131. doi: 10.1056/NEJMoa2114897.