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Randomized Controlled Trial
. 2023 Sep 5;6(9):e2334889.
doi: 10.1001/jamanetworkopen.2023.34889.

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)

Valerie Y Chock  1 , Haresh Kirpalani  2 , Edward F Bell  3 , Sylvia Tan  4 , Susan R Hintz  1 , M Bethany Ball  1 , Emily Smith  4 , Abhik Das  5 , Yvonne C Loggins  6 , Beena G Sood  7 , Lina F Chalak  8 , Myra H Wyckoff  8 , Stephen D Kicklighter  9 , Kathleen A Kennedy  10 , Ravi M Patel  6 , Waldemar A Carlo  11 , Karen J Johnson  3 , Kristi L Watterberg  12 , Pablo J Sánchez  13 , Abbot R Laptook  14 , Ruth B Seabrook  13 , C Michael Cotten  15 , Toni Mancini  2 , Gregory M Sokol  16 , Robin K Ohls  12   17 , Anna Maria Hibbs  18 , Brenda B Poindexter  19 , Anne Marie Reynolds  20 , Sara B DeMauro  21 , Sanjay Chawla  7 , Mariana Baserga  17 , Michele C Walsh  22 , Rosemary D Higgins  22   23 , Krisa P Van Meurs  1 ; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
Collaborators, Affiliations
Randomized Controlled Trial

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)

Valerie Y Chock et al. JAMA Netw Open. .

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.

Trial registration: ClinicalTrials.gov Identifier: NCT01702805.

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Conflict of interest statement

Conflict of Interest Disclosures: Drs Chock, Kirpalani, Bell, Hintz, Das, Sood, Chalak, Wyckoff, Kicklighter, Kennedy, Patel, Carlo, Watterberg, Sanchez, Laptook, Seabrook, Cotten, Sokol, Ohls, Hibbs, Poindexter, Reynolds, DeMauro, Chawla, Baserga, Walsh, Higgins, and Van Meurs and Mses Tan, Ball, Smith, Loggins, Johnson, and Mancini reported grants from the National Heart, Lung, and Blood Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development during the conduct of the study. Drs Patel and Ohls reported nonfinancial support from Medtronic Equipment outside the submitted work. Dr Carlo reported serving on the board for Mednax outside the submitted work. Dr Sokol reported grants from Thrasher Research Fund and contracted research with Mallinckrodt Pharmaceuticals, Airway Therapeutics, and Icon Clinical Research outside the submitted work. Dr DeMauro reported grants from the Thrasher Researcher Fund outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Change in Near-Infrared Spectroscopy (NIRS) Measures with Transfusion by Hemoglobin (Hgb) Threshold Group
In the first 28 days after birth, cerebral saturation (Csat) and mesenteric saturation (Msat) increased after packed red blood cell transfusion, while cerebral fractional tissue oxygen extraction (cFTOE) and mesenteric fractional tissue oxygen extraction (mFTOE) decreased. However, changes in NIRS measures were not significantly different between the high– and low–Hgb threshold groups for Csat, cFTOE, Msat, or mFTOE.
Figure 2.
Figure 2.. Pretransfusion Near-Infrared Spectroscopy (NIRS) Measures by Hemoglobin (Hgb) Threshold Group
A, Pretransfusion cerebral saturation (Csat) in the first 28 days after birth in the high– compared to low–Hgb threshold groups. B, Pretransfusion cerebral fractional tissue oxygen extraction (cFTOE) in the first 28 days after birth in the high– compared to low–Hgb threshold groups.
Figure 3.
Figure 3.. Factors Associated With Death or Neurodevelopmental Impairment (NDI) From Classification and Regression Tree Analysis
Csat indicates pretransfusion cerebral saturation.
See this image and copyright information in PMC

References

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