Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia

Authors

Kristi L. Watterberg, University of New Mexico Health Sciences Center, Albuquerque, New Mexico
Michele C. Walsh, Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, Ohio
Lei Li, Social, Statistical, and Environmental Sciences Unit, RTI International, Research Triangle Park
Sanjay Chawla, Department of Pediatrics, Wayne State University, Detroit, Michigan; Department of Pediatrics, Wayne State University, Detroit, Michigan
Carl T. D'Angio, University of Rochester School of Medicine and Dentistry, Rochester, New York
Ronald N Goldberg, Department of Pediatrics, Duke University, Durham, North Carolina
Susan R. Hintz, Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, California
Matthew M Laughon, Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
Bradley A. Yoder, Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah
Kathleen A. Kennedy, Department of Pediatrics, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, Texas
Georgia E. McDavid, Department of Pediatrics, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, Texas
Conra Backstrom-Lacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico
Abhik Das, Social, Statistical, and Environmental Sciences Unit, RTI International, Rockville, Maryland
Margaret M. Crawford, Social, Statistical, and Environmental Sciences Unit, RTI International, Rockville, Maryland
Martin Keszler, Department of Pediatrics, Women and Infants Hospital, Brown University, Providence, RI
Gregory M. Sokol, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana
Brenda B. Poindexter, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Emory University School of Medicine, Department of Pediatrics, Children's Healthcare of Atlanta, Atlanta, Georgia
Namasivayam Ambalavanan, Division of Neonatology, University of Alabama at Birmingham, Birmingham, Alabama
Anna Maria Hibbs, Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, Ohio
William E. Truog, Department of Pediatrics, Children's Mercy Hospital, Kansas City, MO
Barbara Schmidt, Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
Myra H. Wyckoff, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
Amir M. Khan, Department of Pediatrics, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, Texas
Meena Garg, Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, California
Patricia R. Chess, University of Rochester School of Medicine and Dentistry, Rochester, New York
Anne M. Reynolds, Department of Pediatrics, University of Buffalo Women's and Children's Hospital of Buffalo, Buffalo, New York
Mohannad Moallem, Department of Pediatrics, Nationwide Children's Hospital, Ohio State University College of Medicine, Columbus, Ohio
Edward F. Bell, Department of Pediatrics, University of Iowa, Iowa City, Iowa
Lauritz R. Meyer, Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, South Dakota
Ravi M. Patel, Emory University School of Medicine, Department of Pediatrics, Children's Healthcare of Atlanta, Atlanta, Georgia
Krisa P. Van Meurs, Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, California
C Michael Cotten, Department of Pediatrics, Duke University, Durham, North Carolina
Elisabeth C. McGowan, Department of Pediatrics, Women and Infants Hospital, Brown University, Providence, RI
Abbey C. Hines, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana
Stephanie Merhar, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
Myriam Peralta-Carcelen, Division of Neonatology, University of Alabama at Birmingham, Birmingham, Alabama
Deanne E. Wilson-Costello, Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, Ohio
Howard W. Kilbride, Department of Pediatrics, Children's Mercy Hospital, Kansas City, MO
Sara B. DeMauro, Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
Roy J. Heyne, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
Ricardo A. Mosquera, Department of Pediatrics, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, Texas
Girija Natarajan, Department of Pediatrics, Wayne State University, Detroit, Michigan
Isabell B. Purdy, Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, California
Jean R. Lowe, University of New Mexico Health Sciences Center, Albuquerque, New Mexico
Nathalie L. Maitre, Department of Pediatrics, Nationwide Children's Hospital, Ohio State University College of Medicine, Columbus, Ohio; Emory University School of Medicine, Department of Pediatrics, Children's Healthcare of Atlanta, Atlanta, Georgia
Heidi M. Harmon, Department of Pediatrics, University of Iowa, Iowa City, Iowa
Laurie A. Hogden, Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, South Dakota
Ira Adams-Chapman, Emory University School of Medicine, Department of Pediatrics, Children's Healthcare of Atlanta, Atlanta, Georgia
Sarah Winter, Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City, Utah
William F. Malcolm, Department of Pediatrics, Duke University, Durham, North Carolina
Rosemary D. Higgins, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; College of Health and Human Services, George Mason University, Fairfax, VA
Eunice Kennedy Shriver NICHD Neonatal Research Network

Document Type

Article

Publication Date

3-24-2022

Abstract

BACKGROUND: Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown.

METHODS: We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tapered over a period of 10 days) or placebo. Mandatory extubation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neurodevelopmental impairment at 22 to 26 months of corrected age.

RESULTS: We enrolled 800 infants (mean [±SD] birth weight, 715±167 g; mean gestational age, 24.9±1.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2%) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9%) in the hydrocortisone group and in 134 of 359 (37.3%) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.0%). Other adverse events were similar in the two groups.

CONCLUSIONS: In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01353313.).

Publisher

Massachusetts Medical Society.

Publication Title

The New England journal of medicine

ISSN

1533-4406

Volume

386

Issue

12

First Page

1121

Last Page

1131

DOI

10.1056/NEJMoa2114897

Recommended Citation

Watterberg KL, Walsh MC, Li L, Chawla S, D'Angio CT, Goldberg RN, Hintz SR, Laughon MM, Yoder BA, Kennedy KA, McDavid GE, Backstrom-Lacy C, Das A, Crawford MM, Keszler M, Sokol GM, Poindexter BB, Ambalavanan N, Hibbs AM, Truog WE, Schmidt B, Wyckoff MH, Khan AM, Garg M, Chess PR, Reynolds AM, Moallem M, Bell EF, Meyer LR, Patel RM, Van Meurs KP, Cotten CM, McGowan EC, Hines AC, Merhar S, Peralta-Carcelen M, Wilson-Costello DE, Kilbride HW, DeMauro SB, Heyne RJ, Mosquera RA, Natarajan G, Purdy IB, Lowe JR, Maitre NL, Harmon HM, Hogden LA, Adams-Chapman I, Winter S, Malcolm WF, Higgins RD; Eunice Kennedy Shriver NICHD Neonatal Research Network. Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia. N Engl J Med. 2022 Mar 24;386(12):1121-1131. doi: 10.1056/NEJMoa2114897. PMID: 35320643; PMCID: PMC9107291.