Article
Author: Muthig, Greg ; Eggleston, Barry ; Moses, Mary Beth ; Schaefer, Susan T. ; Gunn, Susan ; Baugher, Hallie ; Fisher, Kimberley A. ; Earhart, Beth A. ; Purnell, Jessica ; Maxson, Earl ; Chopko, Stephanie A. ; Patel, Ravi M. ; Schmidt, Kelly ; Bara, Rebecca ; Krueger, Casey E. ; Dudley, Juanita ; Gerday, Erick B. ; Leblond, David ; Ball, M. Bethany ; Duncan, Andrea F. ; John, Janice ; Finol Mark, Eduardo ; Schibler, Kurt ; Parlberg, Lindsay ; Cucinotta, Dara M. ; Barks, John ; Vasil, Diana M. ; McDougald, E. Rebecca ; Timan, Christopher J. ; O’Donnell Auman, Jeanette ; D'Angio, Carl T. ; Leach, Corinne ; Higgins, Rosemary D. ; #REF!, #REF! ; Carlton, David P. ; Joyce (deceased), Jeffery ; Stuart, Ashley L. ; Benninger, Kristen L. ; Rau, Carrie A. ; White, Michelle ; Wuertz, Sandra ; Grisby, Cathy ; Taylor, Heather L. ; Allain, Elizabeth ; Newman, Nancy S. ; Bentley, Alexandra ; Slaughter, Jonathan L. ; Parry, D. Melody ; Mackie, Colleen ; Benninger, Kristin L. ; McVoy, Brae ; Heyne, Roy J. ; Reichert, Elizabeth N. ; Zaterka-Baxter, Kristin M. ; Eastman, Diane L. ; Ashley, Patricia L. ; Nelin, Mary Ann ; Tice, Katherine ; Martin, Karen ; Bentley, Barbara ; Myers, Gary J. ; Edwards, Laura ; Hinz Woldt, Eunice ; Vohr, Betty R. ; Bose, Gennie ; Brumbaugh, Jane E. ; Warren, Mollie ; Goldston, Laura A. ; Malcolm, William F. ; Wright, Sharon L. ; Stacey, Sara ; Walker, Jacky R. ; Jensen, Rosemary L. ; Puopolo, Karen M. ; Maitre, Nathalie L. ; Carey, Helen ; Tice, Abbie M. ; Newton, Julia ; Pedroza, Claudia ; White, Donna ; Eubanks, Frances ; Carlson, Martha D. ; McNair, Tara E. ; Panaitescu, Bogdan ; Reich, Brixen A. ; Sokol, Gregory M. ; Abbasi, Soraya ; Kachelmeyer, Jennifer ; Johnson, Karen J. ; Henkes, Lisa ; Grothause, Jennifer L. ; Ohls, Robin K. ; Stringer, Kimberlly ; Waterbury, Jillian ; Zanger, Dinorah ; Herron, Dianne E. ; Schmidt, Barbara ; Broadbent, Megan ; Slaughter, Laurel A. ; Stephens, Emily K. ; Sabaratnam, Premini ; Thompson, Julia ; Ladinsky, Morissa ; Orme, Constance ; Petrie Huitema, Carolyn M. ; Agarwal, Prashant ; Hayes, Devan ; Dhawan, Megan A. ; Laughon, Matthew Maxwell ; Guillet, Ronnie ; Chalak, Lina F. ; Keszler, Mary Lenore ; Guilford, Stephanie ; Flibotte, John ; Hamrick, Shannon E. G. ; Gustafson, Kathryn E. ; Kendrick-Allwood, Salathiel ; Guzman, Alicia ; Schiering, Jessica ; Van Muyden, Sarah ; De Leon, Maria M. ; Woodbury, Kathryn D. ; Siner, Bonnie S. ; Czynski, Adam ; Gentle, Samuel J. ; D’Angio, Carl T. ; Park, Courtney ; Weaver-Lewis, Kimberlee ; Recine, Barbara P. ; Wusthoff, Courtney ; Brion, Luc P. ; Hogden, Laurie A. ; Whitley, Sally ; Roth, Elizabeth ; Domnanovich, Kristy A. ; Harrod, Michelle ; Stoll, Barbara J. ; Sánchez, Pablo J. ; DeMauro, Sara B. ; Baker, Shawna ; Boricha, Fatima ; Bajaj, Monika ; Tud, Tracy L. ; Bann, Carla M. ; Bayard, Annie M. ; Hintz, Susan R. ; Scorsone, Ann Marie ; Mosquera, Ricardo ; Cahill, Tanya E. ; Dysart, Kevin ; Khan, Amir M. ; Wereszczak, Janice Kay ; Cobe, Chelsea ; Twell Boatman, Catherine ; Puentez, Anna E. ; Stein, Melanie ; Marchant, Trisha ; Schrimper, Bailey M. ; Vieira, Elisa ; McGowan, Elizabeth C. ; Burkhardt, Stephanie ; Harmon, Heidi M. ; Hensman, Angelita M. ; Stout, Kelly ; Russell, David ; Minton, Stephen D. ; McGrath, Kandace M. ; Bonifacio, Sonia L. ; DeBattista, Anne M. ; Snyder, Jonathan M. ; Biasini (deceased), Fred J. ; Williams, R. Jordan ; Wilson-Costello, Deanne E. ; White, Diane F. ; Cosby, Shirley S. ; Zorn, William A. ; Childs, Kirsten ; Keszler, Martin ; Goeke, Claire A. ; Tyson, Jon E. ; Talbert, Jennifer ; Coleman, Kelly R. ; Preskitt, Julie ; Baserga, Mariana ; Ziolkowski, Kristina ; Ghavam, Sarvin ; Carter, Sheena L. ; Maffett, Deanna ; Rysavy, Matthew A. ; Van Meurs, Krisa P. ; Bonifacio, Sonia Lomeli ; Watkins, Donna ; Clark, Cynthia L. ; Morshedzadeh, Galina ; Baack, Michelle L. ; Moore, Ryan ; Beckford, Demi R. ; Duran, Joanne ; Mulligan LaRossa, Maureen ; Kent, Alison ; Laroira, Nirupama ; Das, Abhik ; Ellsbury, Dan L. ; Goldberg, Ronald N. ; Kirker, Kristin ; Yost, Kelley ; Crawford, Margaret M. ; Levengood, Katelyn ; Huffman, Lynne C. ; Sewell, Elizabeth ; Li, Emily ; Pavageau, Lara ; Kirpalani, Haresh ; Boylin, Elizabeth ; Laughon, Matthew M. ; Miller, Bethany ; Horihan, Cassandra A. ; Travers, Colm P. ; Lucash, Ryan E. ; Clark, Erna ; Leach, Theresa M. ; Wineski, Lynn ; Rector, Richard V. ; Hartley-McAndrew, Michele E. ; Bernhardt, Janice ; Eichenwald, Eric C. ; Sanders, Amy ; Guerina, Nicholas ; Kennedy, Kathleen A. ; Cavanaugh, Brenna ; Cole Bledsoe, Laura ; Ambalavanan, Namasivayam ; McKee, Shannon L. ; Merzbach, Joan ; Mosquera, Ricardo A. ; Yoder, Bradley A. ; Merhar, Stephanie L. ; McCool, Jacqueline ; Bailey, Kirstin J. ; Lee, Lizette E. ; Tolentino-Plata, Kristine ; Elmont, Jennifer O. ; Trembath, Andrea ; Gutentag, Julie ; Hibbs, Anna Maria ; Chaudhary, Aasma S. ; February, Melissa ; Pietruszewski, Lindsay ; Chock, Valerie Y. ; Rutkowska, Lilia ; Chawla, Sanjay ; Warnimont, Kyrstin ; Collins, Monica V. ; Sana Boral, Debasree ; Bahmani, Dona ; Binion, Kyle ; Faix, Roger G. ; Sheffield, Mark J. ; Mancini, Toni ; Shankaran, Seetha ; Jno-Finn, Chantel J. ; Laptook, Abbot R. ; DeSantis, Brittany ; Vera, Azucena ; St. Pierre, Lucille ; Elenkiwich, Chelsey ; Heyne, Elizabeth T. ; Sepulveda, Pollieanna ; Chowdhury, Dhuly ; McDavid, Georgia Elaine ; Sullivan, Rox Ann ; Bell, Edward F. ; Jones, Rachel ; Small, Kristi L. ; Cunningham, Sean D. ; Lopez, Natalia ; Colaizy, Tarah T. ; Bose, Carl L. ; Reddy, Tina ; Weiss, Hali E. ; Alaniz, Nora I. ; Henning, Megan M. ; Rennie, Kimberly ; Newman, Jamie E. ; Jadcherla, Sudarshan R. ; Carlo, Waldemar A. ; Bottcher, Diane I. ; Wilson Archer, Stephanie ; Arldt-McAlister, Julie ; DeAnda, Maria Elena ; Christensen, Susan ; Bapat, Roopali V. ; Natarajan, Girija ; Beiersdorfer, Traci ; Proud, Melinda S. ; Farooq, Osman ; Reynolds, Anne Marie ; Watson, Victoria E. ; Adams-Chapman (deceased), Ira ; Ramon, Emma ; Smikle, Gloria V. ; Laursen, Judith ; York Chapman, Sheree ; Kicklighter, Stephen D. ; Cotten, C. Michael ; Sperry, Daniel K. ; Stevenson, David K. ; Batterson, Nancy ; Dempsey, Allison G. ; Hartley-McAndrew, Michelle E. ; Probst, Joanne ; Dysart, Kevin C. ; Lewis, Amanda ; Nelin, Leif D. ; Winter, Sarah ; Bapat, Roopali ; Mickelsen, Hena G. ; Mago-Shah, Deesha ; Bremer, Andrew A. ; Alksninis, Barbara ; McKee, Kimberly G. ; Knox, Jordan ; Rhodes-Ryan, Ginger ; Walsh, Michele C. ; Schmelzel, Mendi L. ; Loggins, Yvonne C. ; Hall, Donna J. ; Knoll, Andrea M. ; Luzader, Patricia ; Poindexter, Brenda B. ; Hines, Abbey C. ; Shadd, Julie C. ; Wyckoff, Myra H. ; Polin, Richard A. ; Peralta-Carcelen, Myriam ; Adams, Sally S. ; Phillips, Vivien A. ; Marzec, Laura
ImportanceHypothermia begun less than 6 hours after birth reduces death or disability in infants with encephalopathy due to hypoxia-ischemia at 36 or more weeks’ gestation. Trials of hypothermia for infants younger than 36 weeks’ gestation are lacking.ObjectiveTo assess the probability that hypothermia at less than 6 hours after birth decreases death or disability in infants 33 to 35 weeks’ gestation with moderate or severe hypoxic-ischemic encephalopathy.Design, Setting, and ParticipantsThis randomized clinical trial was conducted between July 2015 and December 2022 for infants 33 to 35 weeks’ gestation with moderate or severe hypoxic-ischemic encephalopathy at less than 6 hours after birth. Bayesian and intention-to-treat analyses were prespecified. The setting included 19 US Neonatal Research Network centers. Data were analyzed from March 2023 to November 2024.InterventionsInfants received unblinded targeted esophageal temperature management. Infants with hypothermia were maintained at 33.5 °C (acceptable 33-34 °C) for 72 hours and then rewarmed. Infants with normothermia were to be maintained at 37 °C (acceptable 36.5-37.3 °C).Main Outcomes and MeasuresComposite of death or disability (moderate or severe) at 18 to 22 months’ corrected age adjusted for level of encephalopathy and center.ResultsA total of 168 infants with hypothermia and normothermia were preterm (mean [SD] age, 34.0 [0.8] weeks’ gestation and 34.1 [0.8] weeks’ gestation, respectively), while 46 of 88 (52%) and 45 of 80 (56%) were male, respectively. Randomization occurred at mean (SD) 4.5 (1.2) hours and 4.5 (1.3) hours for the groups with hypothermia and normothermia, respectively. The primary outcome occurred in 29 of 83 infants (35%) with hypothermia and 20 of 69 infants (29%) with normothermia (adjusted relative risk [hypothermic/normothermic], 1.11; 95% credibility interval, 0.74-2.00), and death occurred in 18 of 88 infants (20%) with hypothermia and 9 of 78 infants (12%) with normothermia (adjusted relative risk, 1.38; 95% credibility interval, 0.79-2.85). Bayesian analysis with neutral prior indicated 74% probability of increased death or disability and 87% probability of increased death with hypothermia.Conclusions and RelevanceAmong infants 33 to 35 weeks’ gestation with hypoxic-ischemic encephalopathy, hypothermia at less than 6 hours’ age did not reduce death or disability at 18 to 22 months’ corrected age.Trial RegistrationClinicalTrials.gov Identifier: NCT01793129