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Randomized Controlled Trial
. 2026 Feb 1;180(2):134-143.
doi: 10.1001/jamapediatrics.2025.4801.

Hydrocortisone in Preterm Infants and School-Age Functional Outcomes: Follow-Up of a Randomized Clinical Trial

Sara B DeMauro  1   2 , Haresh Kirpalani  1   2 , Susan Hintz  3 , Kristi L Watterberg  4 , Victoria Watson  5 , Jean Lowe  4 , Seetha Shankaran  6   7 , Sanjay Chawla  7   8 , Betty Vohr  5 , Michael E Msall  9 , Carl T D'Angio  10 , Bradley A Yoder  11 , Khanh Lai  11 , Sarah Winter  11 , Tarah T Colaizy  12 , Stephanie L Merhar  13 , Kristina Ziolkowski  1 , Carla M Bann  14 , Marissa Trotta  14 , Jamie E Newman  14 , Michele C Walsh  15 , Rosemary D Higgins  15 , Tanya E Cahill  13 , Andrea F Duncan  1   2   16 , Deanne E Wilson-Costello  17 , Myriam Peralta-Carcelen  18 , Hope Arnold  18 , Ricardo A Mosquera  19 , Roy J Heyne  20 , Janell Fuller  4 , Elisabeth C McGowan  5 , Brenna Cavanaugh  10 , Heidi M Harmon  12 , Nathalie L Maitre  21   22 , Mary Lauren Neel  21 , Krisa P Van Meurs  3 , Laurie A Richards  23 , Howard W Kilbride  24 , Abbey C Hines  25 , Girija Natarajan  7   8 , Andrea Trembath  26 , Kristen L Benninger  22 , Kalpashri Kesavan  27 , William F Malcolm  28 , Dinorah Zanger  19 , Ann Marie Reynolds  29 , Martha Carlson  30 , Abhik Das  14 ; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
Collaborators, Affiliations
Randomized Controlled Trial

Hydrocortisone in Preterm Infants and School-Age Functional Outcomes: Follow-Up of a Randomized Clinical Trial

Sara B DeMauro et al. JAMA Pediatr. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr DeMauro reported grants from the National Heart, Lung, and Blood Institute (NHLBI) during the conduct of the study; and grants from the National Institutes of Health (NIH) outside the submitted work. Dr Hintz reported a grant from the NIH during the conduct of the study. Dr Shankaran reported grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) during the conduct of the study. Dr Chawla reported a grant from the NIH during the conduct of the study. Dr D’Angio reported grants from the NIH during the conduct of the study. Dr Yoder reported grants from the NICHD during the conduct of the study. Dr Lai reported grants from the NIH during the conduct of the study. Ms Ziolkowski reported grants from the NIH during the conduct of the study. Dr Bann reported grants from the NHLBI during the conduct of the study. Dr Newman reported grants from the NIH during the conduct of the study. Dr Duncan reported grants from the NICHD during the conduct of the study. Dr Peralta-Carcelen reported grants from the NICHD during the conduct of the study; and a grant from the National Institute on Drug Abuse outside the submitted work. Dr Heyne reported grants from the NIH during the conduct of the study. Dr Maitre reported being a cofounder of and having equity in Thrive Neuromedical outside the submitted work. Dr Hines reported grants from the NIH during the conduct of the study. Dr Benninger reported grants from the NICHD during the conduct of the study; and a grant from the National Institute on Drug Abuse outside the submitted work. Dr Malcolm reported grants from the NICHD during the conduct of the study. Dr Das reported grants from the NIH during the conduct of the study. No other disclosures were reported.

References

    1. DeMauro SB. Neurodevelopmental outcomes of infants with bronchopulmonary dysplasia. Pediatr Pulmonol. 2021;56(11):3509-3517. doi: 10.1002/ppul.25381 - DOI - PubMed
    1. Jensen EA, Dysart K, Gantz MG, et al. The diagnosis of bronchopulmonary dysplasia in very preterm infants: an evidence-based approach. Am J Respir Crit Care Med. 2019;200(6):751-759. doi: 10.1164/rccm.201812-2348OC - DOI - PMC - PubMed
    1. Short EJ, Kirchner HL, Asaad GR, et al. Developmental sequelae in preterm infants having a diagnosis of bronchopulmonary dysplasia: analysis using a severity-based classification system. Arch Pediatr Adolesc Med. 2007;161(11):1082-1087. doi: 10.1001/archpedi.161.11.1082 - DOI - PMC - PubMed
    1. Lapcharoensap W, Bennett MV, Xu X, Lee HC, Dukhovny D. Hospitalization costs associated with bronchopulmonary dysplasia in the first year of life. J Perinatol. 2020;40(1):130-137. doi: 10.1038/s41372-019-0548-x - DOI - PMC - PubMed
    1. Bell EF, Hintz SR, Hansen NI, et al. ; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network . Mortality, in-hospital morbidity, care practices, and 2-year outcomes for extremely preterm infants in the US, 2013-2018. JAMA. 2022;327(3):248-263. doi: 10.1001/jama.2021.23580 - DOI - PMC - PubMed

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