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