Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia.
Airway Extubation
Bronchopulmonary Dysplasia
/ epidemiology
Double-Blind Method
Follow-Up Studies
Glucocorticoids
/ administration & dosage
Humans
Hydrocortisone
/ administration & dosage
Infant, Extremely Premature
Infant, Newborn
Infant, Premature
Neurodevelopmental Disorders
/ epidemiology
Oxygen Inhalation Therapy
Respiration, Artificial
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
24 03 2022
24 03 2022
Historique:
entrez:
23
3
2022
pubmed:
24
3
2022
medline:
31
3
2022
Statut:
ppublish
Résumé
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. 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. 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. 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.).
Sections du résumé
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.).
Identifiants
pubmed: 35320643
doi: 10.1056/NEJMoa2114897
pmc: PMC9107291
mid: NIHMS1804913
doi:
Substances chimiques
Glucocorticoids
0
Hydrocortisone
WI4X0X7BPJ
Banques de données
ClinicalTrials.gov
['NCT01353313']
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1121-1131Subventions
Organisme : NICHD NIH HHS
ID : UG1 HD087226
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR77
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000454
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD027904
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR003142
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR1117
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD068263
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD021373
Pays : United States
Organisme : NICHD NIH HHS
ID : U01 HD036790
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002538
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD068270
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD068244
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD027853
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000042
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD087229
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000006
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR93
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD040689
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD053089
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000093
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000442
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR6
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD027856
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR42
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD034216
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR454
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000041
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD068284
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD021385
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD040492
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD021364
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD027880
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000105
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001117
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000077
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD053109
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD027851
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR41
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR105
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD068278
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR442
Pays : United States
Organisme : NICHD NIH HHS
ID : U24 HD095254
Pays : United States
Investigateurs
Richard A Polin
(RA)
Abbot R Laptook
(AR)
Betty R Vohr
(BR)
Angelita M Hensman
(AM)
Elisa Vieira
(E)
Lucille St Pierre
(LS)
Robert T Burke
(RT)
Barbara Alksninis
(B)
Melinda Caskey
(M)
Laurie Hoffman
(L)
Katharine Johnson
(K)
Mary L Keszler
(ML)
Andrea Knoll
(A)
Teresa M Leach
(TM)
Emily Little
(E)
Bonnie E Stephens
(BE)
Victoria E Watson
(VE)
Allison H Payne
(AH)
Nancy S Newman
(NS)
Bonnie S Siner
(BS)
Monika Bhola
(M)
Gulgun Yalcinkaya
(G)
Eugenia K Pallotto
(EK)
Cheri Gauldin
(C)
Anne Holmes
(A)
Kathy Johnson
(K)
Allison Scott
(A)
Kurt Schibler
(K)
Kimberly Yolton
(K)
Traci Beiersdorfer
(T)
Tanya E Cahill
(TE)
Juanita Dudley
(J)
Teresa L Gratton
(TL)
Cathy Grisby
(C)
Kristin Kirker
(K)
Julia Thompson
(J)
Sandra Wuertz
(S)
Ricki F Goldstein
(RF)
Patricia L Ashley
(PL)
Deesha Mago-Shah
(D)
Mollie Warren
(M)
Joanne Finkle
(J)
Kimberley A Fisher
(KA)
Kathryn E Gustafson
(KE)
Carl L Bose
(CL)
Janice Bernhardt
(J)
Gennie Bose
(G)
Janice Wereszczak
(J)
Diane Warner
(D)
Jennifer Talbert
(J)
Cindy Clark
(C)
Stephen D Kicklighter
(SD)
Alexandra Bentley
(A)
Laura Edwards
(L)
Ginger Rhodes-Ryan
(G)
Donna White
(D)
David P Carlton
(DP)
Barbara J Stoll
(BJ)
Ellen C Hale
(EC)
Yvonne Loggins
(Y)
Diane Bottcher
(D)
Sheena L Carter
(SL)
Salathiel Kendrick-Allwood
(S)
Maureen Mulligan LaRossa
(M)
Colleen Mackie
(C)
Gloria Smikle
(G)
Lynn C Comerford
(LC)
Judith Laursen
(J)
Amy Sanders
(A)
Andrew A Bremer
(AA)
Stephanie Wilson Archer
(S)
Lu Ann Papile
(LA)
Heidi Harmon
(H)
Carolyn Lytle
(C)
Dianne E Herron
(DE)
Susan Gunn
(S)
Lucy Smiley
(L)
Leslie Dawn Wilson
(LD)
Jon E Tyson
(JE)
Andrea F Duncan
(AF)
Nora Alaniz
(N)
Elizabeth Allain
(E)
Julie Arldt-McAlister
(J)
Debasree Sana Boral
(DS)
Katrina Burson
(K)
Allison G Dempsey
(AG)
Elizabeth Eason
(E)
Patricia W Evans
(PW)
Carmen Garcia
(C)
Charles Green
(C)
Donna J Hall
(DJ)
Margarita Jiminez
(M)
Janice John
(J)
Patrick M Jones
(PM)
M Layne Lillie
(ML)
Karen Martin
(K)
Sara C Martin
(SC)
Carrie M Mason
(CM)
Georgia E McDavid
(GE)
Shannon L McKee
(SL)
Michelle Poe
(M)
Kimberly Rennie
(K)
Shawna L Rodgers
(SL)
Saba Khan Siddiki
(SK)
Daniel Sperry
(D)
Emily K Stephens
(EK)
Patti L Pierce Tate
(PL)
Sharon L Wright
(SL)
Pablo J Sánchez
(PJ)
Leif D Nelin
(LD)
Sudarshan R Jadcherla
(SR)
Jonathan L Slaughter
(JL)
Patricia Luzader
(P)
Stephanie Burkhardt
(S)
Helen Carey
(H)
Michelle Chao
(M)
Erna Clark
(E)
Erin Fearns
(E)
Christine A Fortney
(CA)
Aubrey Fowler
(A)
Jennifer Grothause
(J)
Julie Gutentag
(J)
Cole Hague
(C)
Jacqueline McCool
(J)
Mary Ann Nelin
(MA)
Courtney Park
(C)
Lindsay Pietruszewski
(L)
Jessica Purnell
(J)
Julie Shadd
(J)
Kristi Small
(K)
Melanie Stein
(M)
Margaret Sullivan
(M)
Rox Ann Sullivan
(RA)
Christopher J Timan
(CJ)
Keith O Yeates
(KO)
Lina Yoseff-Salameh
(L)
Sarah A Keim
(SA)
Julia Newton
(J)
Katelyn Levengood
(K)
Nancy Batterson
(N)
Courtney Rice
(C)
Dennis Wallace
(D)
Carla M Bann
(CM)
Marie G Gantz
(MG)
Jeanette O'Donnell Auman
(J)
Jenna Gabrio
(J)
David Leblond
(D)
Jamie E Newman
(JE)
Carolyn M Petrie Huitema
(CM)
Annie vonLehmden
(A)
Kristin M Zaterka-Baxter
(KM)
David K Stevenson
(DK)
Valerie Y Chock
(VY)
M Bethany Ball
(MB)
Barbara Bentley
(B)
Ritu Chitkara
(R)
Alexis S Davis
(AS)
Maria Elena DeAnda
(ME)
Anne M DeBattista
(AM)
Beth Earhart
(B)
Lynne C Huffman
(LC)
Casey E Krueger
(CE)
Ryan E Lucash
(RE)
Melinda S Proud
(MS)
Elizabeth N Hitchner Reichert
(EN)
Dharshi Sivakumar
(D)
Heather Taylor
(H)
Hali E Weiss
(HE)
Waldemar A Carlo
(WA)
Monica V Collins
(MV)
Shirley S Cosby
(SS)
Fred J Biasini
(FJ)
Kristy A Domnanovich
(KA)
Tara E McNair
(TE)
Vivien A Phillips
(VA)
Sally Whitley
(S)
Sheree York Chapman
(S)
Uday Devaskar
(U)
Teresa Chanlaw
(T)
Rachel Geller
(R)
Tarah T Colaizy
(TT)
John A Widness
(JA)
Jane E Brumbaugh
(JE)
Heidi M Harmon
(HM)
Karen J Johnson
(KJ)
Jacky R Walker
(JR)
Claire A Goeke
(CA)
Mendi L Schmelzel
(ML)
Diane L Eastman
(DL)
Michelle L Baack
(ML)
Laurie A Hogden
(LA)
Lauritz Meyer
(L)
Megan M Henning
(MM)
Chelsey Elenkiwich
(C)
Megan Broadbent
(M)
Sarah Van Muyden
(S)
Dan L Ellsbury
(DL)
Donia B Campbell
(DB)
Tracy L Tud
(TL)
Janell Fuller
(J)
Carol Hartenberger
(C)
Elizabeth Kuan
(E)
Sandra Sundquist Beauman
(S)
Haresh Kirpalani
(H)
Eric C Eichenwald
(EC)
Soraya Abbasi
(S)
Toni Mancini
(T)
Aasma S Chaudhary
(AS)
Dara M Cucinotta
(DM)
Judy C Bernbaum
(JC)
Andrea Freeman Duncan
(A)
Kevin Dysart
(K)
Marsha Gerdes
(M)
Hallam Hurt
(H)
Erik A Jensen
(EA)
Jonathan Snyder
(J)
Kristina Ziolkowski
(K)
Ronnie Guillet
(R)
Gary J Myers
(GJ)
Kyle Binion
(K)
Caitlin Fallone
(C)
Osman Farooq
(O)
Rosemary L Jensen
(RL)
Alison Kent
(A)
Dee Maffett
(D)
Joan Merzbach
(J)
Constance Orme
(C)
Michael G Sacilowski
(MG)
Premini Sabaratnam
(P)
Ann Marie Scorsone
(AM)
Holly I M Wadkins
(HIM)
Karen Wynn
(K)
Kelley Yost
(K)
Satyan Lakshminrusimha
(S)
Praveen Chandrasekharan
(P)
Stephanie Guilford
(S)
Michelle E Hartley-McAndrews
(ME)
Ashley Williams
(A)
William Zorn
(W)
Emily Li
(E)
Jennifer Donato
(J)
Kimberly G McKee
(KG)
Kelly R Coleman
(KR)
Stephen A Bean
(SA)
Carol A Cole
(CA)
Cassandra A Horihan
(CA)
Luc P Brion
(LP)
Diana M Vasil
(DM)
Sally S Adams
(SS)
Lynda Boss
(L)
Lijun Chen
(L)
Maria M De Leon
(MM)
Frances Eubanks
(F)
Alicia Guzman
(A)
Elizabeth Heyne
(E)
Lizette E Lee
(LE)
Helen Lira
(H)
Linda A Madden
(LA)
E Rebecca McDougald
(ER)
Azadeh Mozaffari
(A)
Lara Pavageau
(L)
Pollieanna Sepulveda
(P)
Cathy Twell Boatman
(C)
Kristine Tolentino-Plata
(K)
Azucena Vera
(A)
Jillian Waterbury
(J)
Reshma Wright
(R)
Robin K Ohls
(RK)
Mariana Baserga
(M)
Stephen D Minton
(SD)
Mark J Sheffield
(MJ)
Carrie A Rau
(CA)
Jill Burnett
(J)
Susan Christensen
(S)
Laura Cole Bledsoe
(L)
Sean Cunningham
(S)
Brandy Davis
(B)
Jennifer O Elmont
(JO)
Becky Hall
(B)
Manndi C Loertscher
(MC)
Trisha Marchant
(T)
Earl Maxson
(E)
Kandace M McGrath
(KM)
Hena G Mickelsen
(HG)
Galina Morshedzadeh
(G)
D Melody Parry
(DM)
Brixen A Reich
(BA)
Susan T Schaefer
(ST)
Kelly Stout
(K)
Ashley L Stuart
(AL)
Kimberlee Weaver-Lewis
(K)
Kathryn D Woodbury
(KD)
Seetha Shankaran
(S)
Beena G Sood
(BG)
Rebecca Bara
(R)
Prashant Agarwal
(P)
Monika Bajaj
(M)
Kirsten Childs
(K)
Melissa February
(M)
Laura Goldston
(L)
Mary E Johnson
(ME)
Bogdan Panaitescu
(B)
Eunice Hinz Woldt
(E)
John Barks
(J)
Martha Carlson
(M)
Mary K Christensen
(MK)
Diane F White
(DF)
Stephanie A Wiggins
(SA)
Christine A Gleason
(CA)
Marilee C Allen
(MC)
Robert J Boyle
(RJ)
Traci Clemons
(T)
Mary E D'Alton
(ME)
Abhik Das
(A)
T Michael O'Shea
(TM)
Robin Steinhorn
(R)
Steven J Weiner
(SJ)
Marian Willinger
(M)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 Massachusetts Medical Society.
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