Hydrocortisone in Preterm Infants and School-Age Functional Outcomes

Abstract

IMPORTANCE: Bronchopulmonary dysplasia (BPD) is the most common in-hospital morbidity of prematurity, associated with significant long-term medical and neurodevelopmental sequelae and health resource utilization. The Neonatal Research Network (NRN) Hydrocortisone for BPD Trial evaluated the efficacy and safety of hydrocortisone to prevent BPD in high-risk very preterm infants; the impact of hydrocortisone on school-age outcomes in this trial cohort is previously unreported.

OBJECTIVE: To evaluate the impact of neonatal hydrocortisone treatment on early school-age functional motor, cognitive, academic, and pulmonary outcomes among children who participated in the Hydrocortisone for BPD Trial.

DESIGN, SETTING, AND PARTICIPANTS: This prospective long-term cohort study is a follow-up of a randomized clinical trial, the Hydrocortisone for BPD Trial, conducted at 19 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development NRN. Participants, enrolled from August 2011 to February 2018, included intubated infants who had been born before 30 weeks' gestational age and had been mechanically ventilated for at least 7 days by postnatal day 14 to 28. They were eligible for a single, in-person, early school-age visit between corrected age 5 years 0 months and 7 years 11 months, conducted from September 2017 to July 2024. Data analysis was performed from July 2024 to September 2025.

INTERVENTION: Participants were randomized to a 10-day tapering course of hydrocortisone or placebo beginning at 14 to 28 postnatal days.

MAIN OUTCOMES AND MEASURES: Early school-age study visits were performed by certified, masked assessors. The primary outcome of functional impairment was defined as any of the following: cognitive delay, motor delay, academic delay, or poor functional exercise capacity.

RESULTS: The primary outcome was available for 545 of 674 eligible children (80.9%), including 272 children in the hydrocortisone group (152 [55.9%] female; mean [SD] gestational age, 24.9 [1.5] weeks; mean [SD] age at visit, 5.3 [0.6] years) and 273 in the placebo group (108 [39.6%] female; mean [SD] gestational age, 24.8 [1.5] weeks; mean [SD] age at visit, 5.4 [0.6] years). There was no difference in the rate of functional impairment between the hydrocortisone group (194 of 272 children [71.3%]) and the placebo group (200 of 273 children [73.3%]) (adjusted relative risk, 0.99; 95% CI, 0.89-1.10), nor were there differences in the rates of the individual components. Motor delay was the most common impairment (308 of 510 children [60.4%]), followed by poor functional exercise capacity (175 of 484 children [36.2%]).

CONCLUSIONS AND RELEVANCE: In this study, neonatal hydrocortisone treatment of preterm infants with high risk for BPD did not impact functional impairment or its components; nearly three-quarters of the children demonstrated functional impairment at school age.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01353313.