Timing of Red Blood Cell Transfusions and Occurrence of Necrotizing Enterocolitis
Authors: Ariel A. Salas, Elizabeth Gunn, Waldemar A. Carlo, Edward F. Bell, Abhik Das, Cassandra D. Josephson, Ravi M. Patel, Sylvia Tan, Haresh Kirpalani, Richard A. Polin, Abbot R. Laptook, Martin Keszler, Angelita M. Hensman, Emily Little, Lucille St. Pierre, Elisa Vieira, Michele C. Walsh, Anna Maria Hibbs, Nancy S. Newman, Allison H. Payne, Deanne E. Wilson-Costello, Bonnie S. Siner, Monika Bhola, Gulgun Yalcinkaya, William E. Truog, Eugenia K. Pallotto, Howard W. Kilbride, Cheri Gauldin, Anne Holmes, Kathy Johnson, Allison Scott, Brenda B. Poindexter, Stephanie L. Merhar, Kurt Schibler, Cathy Grisby, Kristin Kirker, Sandra Wuertz, Lenora Jackson, Greg Muthig, Juanita Dudley, Robin K. Whyte, C. Michael Cotten, Ronald N. Goldberg, Ricki F. Goldstein, William F. Malcolm, Patricia L. Ashley, Deesha Mago-Shah, Mollie Warren, Joanne Finkle, Kimberley A. Fisher, Kathryn E. Gustafson, Matthew M. Laughon, Carl L. Bose, Janice Bernhardt, Janice Wereszczak, Diane Warner, Jennifer Talbert, Cindy Clark, Stephen D. Kicklighter, Alexandra Bentley, Laura Edwards, Ginger Rhodes-Ryan, Donna White, Ravi M. Patel, David P. Carlton, Barbara J. Stoll, Ira Adams-Chapman, Yvonne Loggins, Ellen C. Hale, Diane Bottcher, Sheena L. Carter, Salathiel Kendrick-Allwood, Maureen Mulligan LaRossa, Colleen Mackie, Gloria Smikle, Lynn C. Comerford, Rosemary D. Higgins, Andrew A. Bremer, Stephanie Wilson Archer, Gregory M. Sokol, Heidi Harmon, Lu Ann Papile, Abbey C. Hines, Dianne E. Herron, Susan Gunn, Lucy Smiley, Jeff Joyce, John A. F. Zupancic, Kathleen A. Kennedy, Jon E. Tyson, Amir M. Khan, Julie Arldt-McAlister, Elizabeth Eason, Carmen Garcia, Donna J. Hall, Karen Martin, Georgia E. McDavid, Shawna L. Rodgers, Emily K. Stephens, Sharon L. Wright, Traci H. Mondoro, Catherine Levy, Pablo J. Sánchez, Leif D. Nelin, Nathalie L. Maitre, Ruth B. Seabrook, Sudarshan R. Jadcherla, Patricia Luzader, Christine A. Fortney, Julie Gutentag, Christopher J. Timan, Kristi Small, Rox Ann Sullivan, Lina Yoseff-Salameh, Jacqueline McCool, Melanie Stein, Erin Fearns, Aubrey Fowler, Jennifer Grothause, Stephanie Burkhardt, Jessica Purnell, Mary Ann Nelin, Helen Carey, Lindsay Pietruszewski, Margaret Sullivan, Julie Shadd, Jennifer Notestine, Cole Hague, Erna Clark, Michelle Chao, Courtney Park, Hallie Baugher, Demi R. Beckford, Bethany Miller, Laura Marzec, Kyrstin Warnimont, Carla M. Bann, Marie G. Gantz, Donald J. Brambilla, Jamie E. Newman, Jenna Gabrio, Margaret M. Crawford, Carolyn M. Petrie Huitema, Jeanette O’Donnel Auman, David Leblond, Annie vonLehmden, Dennis Wallace, Kristin M. Zaterka-Baxter, Krisa P. Van Meurs, David K. Stevenson, Susan R. Hintz, M. Bethany Ball, Valerie Y. Chock, Barbara Bentley, Maria Elena DeAnda, Anne M. DeBattista, Beth Earhart, Lynne C. Huffman, Casey E. Krueger, Ryan E. Lucash, Melinda S. Proud, Elizabeth N. Reichert, Heather Taylor, Hali E. Weiss, Namasivayam Ambalavanan, Monica V. Collins, Shirley S. Cosby, Myriam Peralta Carcelen, Fred J. Biasini, Kristen C. Johnston, Mary Beth Moses, Tara E. McNair, Vivien A. Phillips, Richard V. Rector, Sally Whitley, Kristy A. Domnanovich, Sheree York Chapman, Uday Devaskar, Meena Garg, Isabell B. Purdy, Teresa Chanlaw, Rachel Geller, Tarah T. Colaizy, Jane E. Brumbaugh, John A. Widness, Heidi M. Harmon, Karen J. Johnson, Jacky R. Walker, Claire A. Goeke, Diane L. Eastman, Kristi L. Watterberg, Robin K. Ohls, Conra Backstrom Lacy, Janell Fuller, Mary Hanson, Carol Hartenberger, Elizabeth Kuan, Jean R. Lowe, Sandra Sundquist Beauman, Barbara Schmidt, Sara B. DeMauro, Soraya Abbasi, Toni Mancini, Dana M. Cucinotta, Jonathan Snyder, Aasma S. Chaudhary, Carl T. D’Angio, Ronnie Guillet, Melissa F. Carmen, Gary J. Myers, Kyle Binion, Caitlin Fallone, Osman Farooq, Julianne Hunn, Rosemary L. Jensen, Joan Merzbach, Constance Orme, Ann Marie Scorsone, Holly I. M. Wadkins, Kelley Yost, Satyan Lakshminrusimha, Anne Marie Reynolds, Stephanie Guilford, Michelle E. Hartley-McAndrews, Ashley Williams, William Zorn, Mary Rowan, Dee Maffett, Diane Prinzing, Melissa Bowman, Michael Sacilowski, Daisy Rochesz, Myra H. Wyckoff, Luc P. Brion, Roy J. Heyne, Diana M. Vasil, Sally S. Adams, Maria M. De Leon, Frances Eubanks, Alicia Guzman, Elizabeth Heyne, Lizette E. Lee, Linda A. Madden, Lara Pavageau, Pollieanna Sepulveda, Cathy Twell Boatman, Kristine Tolentino-Plata, Bradley A. Yoder, Mariana Baserga, Stephen D. Minton, Mark J. Sheffield, Carrie A. Rau, Jill Burnett, Susan Christensen, Laura Cole Bledsoe, Jennifer O. Elmont, Trisha Marchant, Earl Maxson, Kandace M. McGrath, Hena G. Mickelsen, D. Melody Parry, Brixen A. Reich, Susan T. Schaefer, Kimberlee Weaver-Lewis, Kathryn D. Woodbury, Seetha Shankaran, Beena G. Sood, Sanjay Chawla, Rebecca Bara, Prashant Agarwal, Monika Bajaj, Kirsten Childs, Melissa February, Laura Goldston, Mary E. Johnson, Girija Natarajan, Bogdan Panaitescu, Eunice Woldt, John Barks, Martha Carlson, Diane F. White
Journal: JAMA Network Open (2024)

Importance Observational studies often report that anemia and red blood cell (RBC) transfusions are associated with a higher risk of necrotizing enterocolitis (NEC) among extremely low-birthweight (ELBW) infants. Objective To evaluate whether there is a temporal association between 72-hour hazard periods of exposure to RBC transfusions and NEC among ELBW infants randomized to either higher or lower hemoglobin transfusion thresholds. Design, Setting, and Participants This post hoc secondary analysis of 1690 ELBW infants who survived to postnatal day 10 enrolled in the Transfusion of Prematures (TOP) randomized multicenter trial between December 1, 2012, and April 12, 2017, was performed between June 2021 and July 2023. Exposures First, the distribution of RBC transfusions and the occurrence of NEC up to postnatal day 60 were examined. Second, 72-hour posttransfusion periods were categorized as hazard periods and the pretransfusion periods of variable duration as control periods. Then, the risk of NEC in posttransfusion hazard periods was compared with that in pretransfusion control periods, stratifying the risk based on randomization group (higher or lower hemoglobin transfusion threshold group). Main Outcomes and Measures The primary outcome was incidence of NEC stage 2 or 3. Secondary outcomes included the incidence rates of NEC within five 10-day intervals, taking into account the number of days at risk. Results Of 1824 ELBW infants randomized during the TOP trial, 1690 were included in the present analysis (mean [SD] gestational age, 26.0 [1.5] weeks; 899 infants [53.2%] were female). After categorizing 4947 hazard periods and 5813 control periods, we identified 133 NEC cases. Fifty-nine of these cases (44.4%) occurred during hazard periods. Baseline and clinical characteristics of infants with NEC during hazard periods did not differ from those of infants with NEC during control periods. The risk of NEC was 11.9 per 1000 posttransfusion hazard periods and 12.7 per 1000 control periods (adjusted risk ratio, 0.95; 95% CI, 0.68-1.32; P = .74). This risk did not differ significantly between randomization groups, but the incidence rate of NEC per 1000 days peaked between postnatal days 20 and 29 in the lower hemoglobin transfusion threshold group. Conclusions and Relevance The findings of this post hoc analysis suggest that, among ELBW infants with the hemoglobin ranges occurring in the TOP trial, exposure to RBC transfusions was not temporally associated with a higher risk of NEC during 72-hour posttransfusion hazard periods. Given that the incidence rate of NEC peaked between postnatal days 20 and 29 among infants with lower hemoglobin values, a more in-depth examination of this at-risk period using larger data sets is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT01702805