Neonatal Hydrocortisone fails to Improve Outcomes in kids with BPD at School going Age: JAMA

Infants born extremely premature and requiring prolonged mechanical ventilation are at high risk for BPD and its lifetime complications. Corticosteroids, such as hydrocortisone, have been investigated to decrease inflammation and ventilator dependency during the neonatal period. However, concern about potential neurodevelopmental effects of early corticosteroids remains.

This prospective long-term cohort study followed participants from the NRN Hydrocortisone for BPD randomized clinical trial, conducted at 19 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Infants were enrolled between August 2011 and February 2018 and were eligible if they were born at less than 30 weeks’ gestation, intubated, and mechanically ventilated for at least 7 days between postnatal days 14 and 28. Early school-age follow-up visits occurred between September 2017 and July 2024, with assessments performed at corrected ages 5 years 0 months to 7 years 11 months. Data analysis was completed from July 2024 to September 2025.

Participants were randomly assigned to receive either a 10-day tapering course of hydrocortisone or placebo, starting between 14 and 28 postnatal days. Certificated and masked examiners performed standardized assessments at school age. The primary outcome was functional impairment, defined as the presence of cognitive delay, motor delay, academic delay, or poor functional exercise capacity.

Key Findings

• Primary outcome data were available for 545 of 674 eligible children (80.9%), including 272 children in the hydrocortisone group and 273 in the placebo group.

• In the hydrocortisone group, 152 children (55.9%) were female, with a mean (SD) gestational age of 24.9 (1.5) weeks and a mean (SD) age at assessment of 5.3 (0.6) years. In the placebo group, 108 children (39.6%) were female, with a mean (SD) gestational age of 24.8 (1.5) weeks and a mean (SD) assessment age of 5.4 (0.6) years.

• Functional impairment occurred in 194 of 272 children (71.3%) in the hydrocortisone group and 200 of 273 children (73.3%) in the placebo group, with an adjusted relative risk of 0.99 (95% CI, 0.89–1.10).

• No significant differences were observed across individual impairment components. Motor delay was the most prevalent impairment across both groups: 308 of 510 children (60.4%); followed by poor functional exercise capacity: 175 of 484 children (36.2%).

• Rates of cognitive delay and academic delay did not differ significantly between treatment groups.

In this long-term follow-up of a randomized clinical trial, neonatal hydrocortisone treatment for infants at high risk of bronchopulmonary dysplasia did not improve functional motor, cognitive, academic, or pulmonary outcomes at early school age. Almost three-quarters of the children evidenced functional impairment, underscoring further need for innovation in both prevention strategies and long-term supportive care for the extremely preterm infant.

Reference:

DeMauro SB, Kirpalani H, Hintz S, et al. Hydrocortisone in Preterm Infants and School-Age Functional Outcomes: Follow-Up of a Randomized Clinical Trial. JAMA Pediatr. Published online December 08, 2025. doi:10.1001/jamapediatrics.2025.4801