Hydrocortisone in Preterm Infants and School-Age Functional Outcomes: Follow-Up of a Randomized Clinical Trial.
| Title: | Hydrocortisone in Preterm Infants and School-Age Functional Outcomes: Follow-Up of a Randomized Clinical Trial. |
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| Authors: | DeMauro SB; Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.; University of Pennsylvania Perelman School of Medicine, Philadelphia.; Kirpalani H; Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.; University of Pennsylvania Perelman School of Medicine, Philadelphia.; Hintz S; Stanford University School of Medicine, Palo Alto, California.; Watterberg KL; University of New Mexico Health Sciences Center, Albuquerque.; Watson V; Women & Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence.; Lowe J; University of New Mexico Health Sciences Center, Albuquerque.; Shankaran S; University of Texas at Austin, Dell Children's Hospital, Austin.; Wayne State University, Detroit, Michigan.; Chawla S; Wayne State University, Detroit, Michigan.; Children's Hospital of Michigan, Central Michigan University, Detroit.; Vohr B; Women & Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence.; Msall ME; Comer Children's Hospital, Kennedy Research Center on Intellectual and Developmental Disabilities of the University of Chicago, Chicago, Illinois.; D'Angio CT; University of Rochester School of Medicine and Dentistry, Rochester, New York.; Yoder BA; University of Utah School of Medicine, Salt Lake City.; Lai K; University of Utah School of Medicine, Salt Lake City.; Winter S; University of Utah School of Medicine, Salt Lake City.; Colaizy TT; University of Iowa, Iowa City.; Merhar SL; Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.; Ziolkowski K; Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.; Bann CM; Analytics Division, RTI International, Research Triangle Park, North Carolina.; Trotta M; Analytics Division, RTI International, Research Triangle Park, North Carolina.; Newman JE; Analytics Division, RTI International, Research Triangle Park, North Carolina.; Walsh MC; Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.; Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.; Cahill TE; Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.; Duncan AF; Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.; University of Pennsylvania Perelman School of Medicine, Philadelphia.; Associate Editor, JAMA Pediatrics.; Wilson-Costello DE; Rainbow Babies and Children's Hospital, Cleveland, Ohio.; Peralta-Carcelen M; University of Alabama University Hospital, Birmingham.; Arnold H; University of Alabama University Hospital, Birmingham.; Mosquera RA; Children's Memorial Hermann Hospital, Houston, Texas.; Heyne RJ; Parkland Memorial Hospital, Dallas, Texas.; Fuller J; University of New Mexico Health Sciences Center, Albuquerque.; McGowan EC; Women & Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence.; Cavanaugh B; University of Rochester School of Medicine and Dentistry, Rochester, New York.; Harmon HM; University of Iowa, Iowa City.; Maitre NL; Emory University Hospital Midtown, Atlanta, Georgia.; Nationwide Children's Hospital, Ohio State University Wexner Medical Center, Columbus.; Neel ML; Emory University Hospital Midtown, Atlanta, Georgia.; Van Meurs KP; Stanford University School of Medicine, Palo Alto, California.; Richards LA; Stanford Health, Palo Alto, California.; Kilbride HW; Children's Mercy Kansas City, Kansas City, Kansas.; Hines AC; Riley Hospital for Children, Indianapolis, Indiana.; Natarajan G; Wayne State University, Detroit, Michigan.; Children's Hospital of Michigan, Central Michigan University, Detroit.; Trembath A; University of North Carolina at Chapel Hill, Chapel Hill.; Benninger KL; Nationwide Children's Hospital, Ohio State University Wexner Medical Center, Columbus.; Kesavan K; University of California, Los Angeles.; Malcolm WF; Duke University Hospital, Durham, North Carolina.; Zanger D; Children's Memorial Hermann Hospital, Houston, Texas.; Reynolds AM; University of Buffalo, Buffalo, New York.; Carlson M; C.S. Mott Children's Hospital, University of Michigan Medical Center.; Das A; Analytics Division, RTI International, Research Triangle Park, North Carolina. |
| Corporate Authors: | Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network |
| Source: | JAMA pediatrics [JAMA Pediatr] 2026 Feb 01; Vol. 180 (2), pp. 134-143. |
| Publication Type: | Journal Article; Randomized Controlled Trial; Multicenter Study |
| Language: | English |
| Journal Info: | Publisher: American Medical Association Country of Publication: United States NLM ID: 101589544 Publication Model: Print Cited Medium: Internet ISSN: 2168-6211 (Electronic) Linking ISSN: 21686203 NLM ISO Abbreviation: JAMA Pediatr Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Chicago, IL : American Medical Association, [2013]- |
| MeSH Terms: | Hydrocortisone*/therapeutic use ; Hydrocortisone*/administration & dosage ; Bronchopulmonary Dysplasia*/prevention & control ; Child Development*/drug effects ; Anti-Inflammatory Agents*/therapeutic use; Humans ; Female ; Male ; Infant, Newborn ; Follow-Up Studies ; Infant, Premature ; Child, Preschool ; Prospective Studies ; Child ; Treatment Outcome |
| 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. |
| Grant Information: | UG1 HD068263 United States HD NICHD NIH HHS; U10 HD021373 United States HD NICHD NIH HHS; UG1 HD087226 United States HD NICHD NIH HHS; U01 HD036790 United States HD NICHD NIH HHS; UG1 HD068270 United States HD NICHD NIH HHS; UG1 HD053089 United States HD NICHD NIH HHS; U10 HD040689 United States HD NICHD NIH HHS; UG1 HD027856 United States HD NICHD NIH HHS; UG1 HD027904 United States HD NICHD NIH HHS; UG1 HD027880 United States HD NICHD NIH HHS; UG1 HD053109 United States HD NICHD NIH HHS; UG1 HD027851 United States HD NICHD NIH HHS; UG1 HD104252 United States HD NICHD NIH HHS; UG1 HD068244 United States HD NICHD NIH HHS; UG1 HD027853 United States HD NICHD NIH HHS; UG1 HD112093 United States HD NICHD NIH HHS; UG1 HD087229 United States HD NICHD NIH HHS; UG1 HD040689 United States HD NICHD NIH HHS; UG1 HD034216 United States HD NICHD NIH HHS; UH3 HL137872 United States HL NHLBI NIH HHS; UG1 HD068284 United States HD NICHD NIH HHS; UG1 HD021385 United States HD NICHD NIH HHS; UG1 HD040492 United States HD NICHD NIH HHS; UG1 HD021364 United States HD NICHD NIH HHS; UG1 HD068278 United States HD NICHD NIH HHS; U24 HL137729 United States HL NHLBI NIH HHS; U24 HD095254 United States HD NICHD NIH HHS |
| Contributed Indexing: | Investigator: N Ambalavanan; FJ Biasini; WA Carlo; MV Collins; SS Cosby; KA Domnanovich; TE McNair; VA Phillips; S Whitley; S York Chapman; B Alksninis; RT Burke; M Caskey; AM Hensman; L Hoffman; K Johnson; M Keszler; ML Keszler; AM Knoll; AR Laptook; TM Leach; E Little; JP Mayne; L St Pierre; BE Stephens; E Vieira; P Chandrasekharan; KR Coleman; J Donato; S Guilford; ME Hartley-McAndrew; S Lakshminrusimha; E Li; MG Sacilowski; A Williams; K Wynn; WA Zorn; M Bhola; AM Hibbs; NS Newman; AH Payne; E Roth; BS Siner; G Yalcinkaya; B Alexander; T Beiersdorfer; J Dudley; TL Gratton; C Grisby; D Hayes; L Henkes; LD Jackson; J Jennings; K Kirker; K Meister; BB Poindexter; C Robinson; D Russell; K Schibler; S Stacey; S Tepe; J Thompson; S Wuertz; K Yolton; RA Polin; LP Brion; L Chen; MM De Leon; F Eubanks; A Guzman; ET Heyne; LE Lee; N Lopez; ER McDougald; L Pavageau; AE Puentez; P Sepulveda; K Tolentino-Plata; C Twell Boatman; DM Vasil; A Vera; J Waterbury; MH Wyckoff; PL Ashley; CM Cotten; KA Fisher; RN Goldberg; RF Goldstein; KE Gustafson; D Mago-Shah; J Probst; C Stone; M Warren; I Adams-Chapman; DI Bottcher; DP Carlton; SL Carter; LC Comerford; EC Hale; S Kendrick-Allwood; J Laursen; YC Loggins; C Mackie; M Mulligan LaRossa; RM Patel; A Sanders; E Sewell; GV Smikle; BJ Stoll; NI Alaniz; J Arldt-McAlister; F Boricha; K Burson; AG Dempsey; E Eason; C Garcia; DJ Hall; J John; KA Kennedy; AM Khan; K Martin; SC Martin; GE McDavid; SL McKee; PL Pierce Tate; T Reddy; K Rennie; S Rodgers; MA Rysavy; D Sana Boral; DK Sperry; EK Stephens; JE Tyson; SL Wright; S Gunn; DE Herron; J Joyce; C Lytle; LA Papile; LC Smiley; GM Sokol; LD Wilson; EF Bell; JE Brumbaugh; DL Eastman; CA Goeke; KJ Johnson; ML Schmelzel; JR Walker; JA Widness; DL Ellsbury; TL Tud; C Gauldin; AM Holmes; K Johnson; EK Pallotto; A Scott; WE Truog; N Batterson; S Burkhardt; H Carey; M Chao; E Clark; E Fearns; CA Fortney; A Fowler; JL Grothause; J Gutentag; CD Hague; SR Jadcherla; SA Keim; K Levengood; P Luzader; NL Maitre; J McCool; LD Nelin; MA Nelin; J Newton; C Park; L Pietruszewski; J Purnell; C Rice; PJ Sánchez; JC Shadd; JL Slaughter; KL Small; M Stein; M Sullivan; RA Sullivan; CJ Timan; KO Yeates; L Yossef-Salameh; AA Bremer; S Wilson Archer; S Abbasi; JC Bernbaum; L Betancourt; AS Chaudhary; EC Eichenwald; D Foy; K Friedman; M Gerdes; H Hurt; A Mancini; L McWhorter; B Schmidt; JM Snyder; SA Bean; K Binion; M Bowman; PR Chess; CA Cole; C Fallone; O Farooq; R Guillet; CA Horihan; J Hunn; RL Jensen; R Jones; A Kent; D Maffett; KG McKee; J Merzbach; GJ Myers; C Orme; P Sabaratnam; AM Scorsone; HIM Wadkins; K Yost; MM Crawford; J Gabrio; MG Gantz; D Leblond; J O'Donnell Auman; L Parlberg; CM Petrie Huitema; AM VonLehmden; D Wallace; KM Zaterka-Baxter; ML Baack; M Broadbent; C Elenkiwich; MM Henning; LR Meyer; S Van Muyden; MB Ball; B Bentley; VY Chock; AS Davis; ME DeAnda; AM DeBattista; BA Earhart; EN Hitchner Reichert; LC Huffman; CE Krueger; RE Lucash; KK Morris; MS Proud; BP Recine; L Rutkowska; D Sivakumar; DK Stevenson; HL Taylor; HE Weiss; T Chanlaw; U Devaskar; M Garg; R Geller; IB Purdy; J Bernhardt; CL Bose; CL Clark; MM Laughon; S Makhijani; H Martin; TM O'Shea; J Talbert; G Taylor; DD Warner; JK Wereszczak; C Backstrom Lacy; CH Hartenberger; E Kuan; M Ruffner Hanson; S Sundquist Beauman; J Barks; MK Christensen; DF White; SA Wiggins; S Baker; M Baserga; J Burnett; S Christensen; L Cole Bledsoe; SD Cunningham; JO Elmont; B Hall; MC Loertscher; T Marchant; E Maxson; KM McGrath; HG Mickelsen; SD Minton; G Morshedzadeh; RK Ohls; DM Parry; CA Rau; BA Reich; E Reichman; ST Schaefer; MJ Sheffield; K Stout; AL Stuart; K Weaver-Lewis; KD Woodbury; CA Gleason; A Bentley; L Edwards; SD Kicklighter; G Rhodes-Ryan; D White; P Agarwal; M Bajaj; R Bara; K Childs; M February; LA Goldston; E Hinz Woldt; ME Johnson; J Manning; B Panaitescu; BG Sood |
| Molecular Sequence: | ClinicalTrials.gov NCT01353313 |
| Substance Nomenclature: | WI4X0X7BPJ (Hydrocortisone); 0 (Anti-Inflammatory Agents) |
| Entry Date(s): | Date Created: 20251208 Date Completed: 20260202 Latest Revision: 20260423 |
| Update Code: | 20260423 |
| PubMed Central ID: | PMC12687206 |
| DOI: | 10.1001/jamapediatrics.2025.4801 |
| PMID: | 41359352 |
| Database: | MEDLINE |
Journal Article; Randomized Controlled Trial; Multicenter Study