Tissue Oxygenation Changes After Transfusion and Outcomes in Preterm Infants
Authors: Chock Valerie Y. , Kirpalani Haresh , Bell Edward F. , Tan Sylvia , Hintz Susan R. , Ball M. Bethany , Smith Emily , Das Abhik , Loggins Yvonne C. , Sood Beena G. , Chalak Lina F. , Wyckoff Myra H. , Kicklighter Stephen D. , Kennedy Kathleen A. , Patel Ravi M. , Carlo Waldemar A. , Johnson Karen J. , Watterberg Kristi L. , Sánchez Pablo J. , Laptook Abbot R. , Seabrook Ruth B. , Cotten C. Michael , Mancini Toni , Sokol Gregory M. , Ohls Robin K. , Hibbs Anna Maria , Poindexter Brenda B. , Reynolds Anne Marie , DeMauro Sara B. , Chawla Sanjay , Baserga Mariana , Walsh Michele C. , Higgins Rosemary D. , Van Meurs Krisa P. ,   Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, Wright Sharon L. , Roberts Robin S. , Mondoro Traci H. , Levy Catherine , Nelin Leif D. , Maitre Nathalie L. , 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 , Chan Michelle , Park Courtney , Baugher Hallie , Beckford Demi R. , Miller Bethany , Marzec Laura , Warnimont Kyrstin , Bann Carla M. , Gantz Marie G. , O'Donnell Auman Jeanette , Bayard Annie , Brambilla Donald J. , Crawford Margaret M. , Gabrio Jenna , Newman Jamie E. , Petrie Huitema Carolyn M. , Leblond David , Wallace Dennis , Zaterka-Baxter Kristin M. , Stevenson David K. , Bentley Barbara , DeAnda Maria Elena , DeBattista Anne M. , Earhart Beth , Huffman Lynne C. , Kruger Casey E. , Lucash Ryan E. , Proud Melinda S. , Reichert Elizabeth N. , Sivakumar Dharshi , Taylor Heather , Weiss Hali E. , Ambalavanan Namasivayam , Collins Monica V. , Cosby Shirley S. , Peralta-Carcelen Myriam , Biasini Fred J. , Johnston Kristen C. , Moses Mary Beth , McNair Tara E. , Philips Vivien A. , Rector Richard V. , Whitley Sally , Domnanovich Kristy A. , York Chapman Sheree , Whyte Robin K. , Colaizy Tarah T. , Widness John A. , Brumbaugh Jane E. , Harmon Heidi M. , Walker Jacky R. , Goeke Claire A. , Schmelzel Mendi L. , Eastman Diane L. , Backstrom Lacy Conra , Fuller Janell , Hanson Mary , Hartenberger Carol , Kuan Elizabeth , Lowe Jean R. , Sundquist Beauman Sandra , Eichenwald Eric C. , Schmidt Barbara , Abbasi Soraya , Chaudhary Aasma S. , Cucinotta Dara M. , Bernbaum Judy C. , Gerdes Marsha , Hurt Hallam , Snyder Jonathan , Ziolkowski Kris , D'Angio Carl T. , Guillet Ronnie , Carmen Melissa F. , Myers Gary J. , Binion Kyle , Bowman Melissa , Boylin Elizabeth , Fallone Caitlin , Farooq Osman , Hunn Julianne , Jensen Rosemary L. , Jones Rachel , Merzbach Joan , Orne Constance , Sabaratnam Premini , Scorsone Ann Marie , Wadkins Holly I.M. , Yost Kelly , Lakshminrusimha Satyan , Guilford Stephanie , Hartley-McAndrews Michelle E. , Williams Ashley , Zorn William , Li Emily , Donato Jennifer , McKee Kimberly G. , Coleman Kelly R. , Kent Alison , Brion Luc P. , Heyne Roy J. , Vasil Diana M. , Adams Sally S. , De Leon Maria M. , Eubanks Francis , Guzman Alicia , Heyne Elizabeth , Lee Lizette E. , Madden Linda A. , McDougald E. Rebecca , Pavageau Lara , Sepulveda Pollieanna , Twell Boatman Cathy , Tolentino-Plata Kristine , Vera Azucena , Waterbury Jillian , Yoder Bradley A. , Minton Stephen. D. , Sheffield Mark J. , Rau Carrie A. , Winter Sarah , Baker Shawna , Burnett Jill , Christensen Susan , Cole Bledsoe Laura , Cunningham Sean , Elmont Jennifer O. , Hall Becky , Marshant Trisha , Maxson Earl , McGrath Kandace M. , Mickelsen Hena G. , Morshedzadeh Galina , Parry D. Melody , Reich Brixen A. , Schaefer Susan T. , Stuart Ashley L. , Stout Kelly , Weaver-Lewis Kimberlee , Woodbury Kathryn D. , Shankaran Seetha , Bara Rebecca , Agarwal Prashant , Bajaj Monika , Childs Kirsten , February Melissa , Goldston Laura , Johnson Mary E. , Natarajan Girija , Panaitescu Bogdan , Woldt Eunice 
Published: September 2023

Importance

Preterm infants with varying degrees of anemia have different tissue oxygen saturation responses to red blood cell (RBC) transfusion, and low cerebral saturation may be associated with adverse outcomes.

Objective

To determine whether RBC transfusion in preterm infants is associated with increases in cerebral and mesenteric tissue saturation (Csat and Msat, respectively) or decreases in cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE, respectively) and whether associations vary based on degree of anemia, and to investigate the association of Csat with death or neurodevelopmental impairment (NDI) at 22 to 26 months corrected age.

Design, Setting, and Participants

This was a prospective observational secondary study conducted among a subset of infants between August 2015 and April 2017 in the Transfusion of Prematures (TOP) multicenter randomized clinical trial at 16 neonatal intensive care units of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Preterm neonates with gestational age 22 to 28 weeks and birth weight 1000 g or less were randomized to higher or lower hemoglobin thresholds for transfusion. Data were analyzed between October 2020 and May 2022.

Interventions

Near-infrared spectroscopy monitoring of Csat and Msat.

Main Outcomes and Measures

Primary outcomes were changes in Csat, Msat, cFTOE, and mFTOE after transfusion between hemoglobin threshold groups, adjusting for age at transfusion, gestational age, birth weight stratum, and center. Secondary outcome at 22 to 26 months was death or NDI defined as cognitive delay (Bayley Scales of Infant and Toddler Development-III score &amp;lt;85), cerebral palsy with Gross Motor Function Classification System level II or greater, or severe vision or hearing impairment.

Results

A total of 179 infants (45 [44.6%] male) with mean (SD) gestational age 25.9 (1.5) weeks were enrolled, and valid data were captured from 101 infants during 237 transfusion events. Transfusion was associated with a significant increase in mean Csat of 4.8% (95% CI, 2.7%-6.9%) in the lower–hemoglobin threshold group compared to 2.7% (95% CI, 1.2%-4.2%) in the higher–hemoglobin threshold group, while mean Msat increased 6.7% (95% CI, 2.4%-11.0%) vs 5.6% (95% CI, 2.7%-8.5%). Mean cFTOE and mFTOE decreased in both groups to a similar extent. There was no significant change in peripheral oxygen saturation (SpO2) in either group (0.2% vs −0.2%). NDI or death occurred in 36 infants (37%). Number of transfusions with mean pretransfusion Csat less than 50% was associated with NDI or death (odds ratio, 2.41; 95% CI, 1.08-5.41; P = .03).

Conclusions and Relevance

In this secondary study of the TOP randomized clinical trial, Csat and Msat were increased after transfusion despite no change in SpO2. Lower pretransfusion Csat may be associated with adverse outcomes, supporting further investigation of targeted tissue saturation monitoring in preterm infants with anemia.

Trial Registration

ClinicalTrials.gov Identifier: NCT01702805