Tissue Oxygenation Changes After Transfusion and Outcomes in Preterm Infants: A Secondary Near-Infrared Spectroscopy Study of the Transfusion of Prematures Randomized Clinical Trial (TOP NIRS)

• Type of Material: Article
• Authors: Valerie Y. Chock, Stanford University; Haresh Kirpalani, University of Pennsylvania; Edward F. Bell, University of Iowa; Sylvia Tan, RTI International; Susan R. Hintz, Stanford University; M. Bethany Ball, Stanford University; Emily Smith, RTI International; Abhik Das, RTI International; Yvonne C. Loggins, Emory University; Beena G. Sood, Wayne State University; Lina F. Chalak, University of Texas, Southwestern; Myra H. Wyckoff, University of Texas, Southwestern; Stephen D. Kicklighter, WakeMed Health and Hospital; Kathleen A. Kennedy, University of Texas, Houston; Ravi Mangal Patel, Emory University; Waldemar A. Carlo, University of Alabama at Birmingham; Karen J. Johnson, University of Iowa; Kristi L. Watterberg, University of New Mexico; Pablo J. Sánchez, The Ohio State University; Abbot R. Laptook, Brown University; Ruth B. Seabrook, The Ohio State University; C. Michael Cotten, Duke University; Toni Mancini, University of Pennsylvania; Gregory M. Sokol, Indiana University; Robin K. Ohls, University of New Mexico; Anna Maria Hibbs, Case Western Reserve University; Brenda B. Poindexter, University of Cincinnati; Anne Marie Reynolds, University of Buffalo; Sara B. DeMauro, Children's Hospital of Philadelphia; Sanjay Chawla, Wayne State University; Mariana Baserga, University of Utah; Michele C. Walsh, National Institutes of Health; Rosemary D. Higgins, Florida Gulf Coast University; Krisa P. Van Meurs, Stanford University
• Language: English
• Date: 2023-09-21
• Publisher: JAMA
• Publication Version: Final Published Version
• Copyright Statement: 2023 Chock VY et al. JAMA Network Open.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1001%2Fjamanetworkopen.2023.34889
• Title of Journal or Parent Work: JAMA Network Open
• Volume: 6
• Issue: 9
• Start Page: e2334889
• Grant/Funding Information: This study was supported by loan of equipment from Medtronic. Grant support for the Neonatal Research Network was provided by the National Heart, Lung, and Blood Institute (R01HL12216701A1, U01 HL112776 and U01 HL112748), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (U10 HD21373, UG1 HD21364, UG1 HD21385, UG1 HD27851, UG1 HD27853, UG1 HD27856, UG1 HD27880,UG1 HD27904, UG1 HD34216, UG1 HD36790, UG1 HD40492, UG1 HD40689, UG1 HD53089, UG1 HD53109, UG1 HD68244, UG1 HD68270, UG1 HD68278, UG1 HD68263, UG1 HD68284; UG1 HD87226, UG1 HD87229), and the National Center for Advancing Translational Sciences (UL1 TR6, UL1 TR41, UL1 TR42, UL1 TR77, UL1 TR93, UL1 TR105, UL1 TR442, UL1 TR454, UL1 TR1117). The National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Heart, Lung, and Blood Institute, the National Center for Research Resources, and the National Center for Advancing Translational Sciences provided grant support for the Neonatal Research Network’s Transfusion of Preemies (TOP) trial through cooperative agreements.
• Keywords: tissue oxygen; red blood cell transfusion; neurodevelopment; cerebral saturation
• Research Categories: Health Sciences, General; Biology, General

Abstract

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 <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.