The transfusion of prematures early school age follow-up (TOP 5): protocol for a longitudinal cohort study

Abstract Background Anemia of prematurity is a common concern for extremely low birth weight (ELBW) patients in the neonatal intensive care unit. The hemoglobin threshold at which the benefits of red blood cell transfusion outweigh the risks is unknown. The NICHD Neonatal Research Network Transfusio...

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Main Authors: Amy L. Conrad, Sara B. DeMauro, Haresh Kirpalani, Kristina Ziolkowski, Susan R. Hintz, Betty R. Vohr, Victoria Watson, Tarah T. Colaizy, Edward F. Bell, Jane E. Brumbaugh, Carla M. Bann, Sylvia M. Tan, Jamie E. Newman, Abhik Das
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Language:English
Published: BMC 2025-05-01
Series:BMC Pediatrics
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Online Access:https://doi.org/10.1186/s12887-025-05732-3
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author Amy L. Conrad
Sara B. DeMauro
Haresh Kirpalani
Kristina Ziolkowski
Susan R. Hintz
Betty R. Vohr
Victoria Watson
Tarah T. Colaizy
Edward F. Bell
Jane E. Brumbaugh
Carla M. Bann
Sylvia M. Tan
Jamie E. Newman
Abhik Das
author_facet Amy L. Conrad
Sara B. DeMauro
Haresh Kirpalani
Kristina Ziolkowski
Susan R. Hintz
Betty R. Vohr
Victoria Watson
Tarah T. Colaizy
Edward F. Bell
Jane E. Brumbaugh
Carla M. Bann
Sylvia M. Tan
Jamie E. Newman
Abhik Das
author_sort Amy L. Conrad
collection DOAJ
description Abstract Background Anemia of prematurity is a common concern for extremely low birth weight (ELBW) patients in the neonatal intensive care unit. The hemoglobin threshold at which the benefits of red blood cell transfusion outweigh the risks is unknown. The NICHD Neonatal Research Network Transfusion of Prematures (TOP) Trial evaluated whether higher (more liberal) hemoglobin transfusion thresholds resulted in improved survival without neurodevelopmental impairment at 22–26 months’ corrected age. A total of 1824 ELBW infants born at 22–28 weeks’ gestation were enrolled in the trial and randomized to either a restrictive or liberal set of red blood cell transfusion thresholds. Longer-term impacts of different transfusion thresholds in treatment for anemia of prematurity remain unknown. The Transfusion of Prematures Early School Age Follow-up (TOP 5) Study extends follow-up of all surviving children enrolled in the TOP Trial until early school age. It aims to assess longer-term cognitive and functional effects of differing transfusion thresholds in the newborn period for anemia in this large, multicenter cohort. Methods Parents of surviving trial participants complete telephone questionnaires when their children are 3 and 4 years’ corrected age. A single in-person study visit takes place at early school age (5 years, 0 months to 7 years, 11 months’ corrected age). Children undergo a multidimensional assessment of functional outcomes, and parents complete a battery of questionnaires. Discussion The TOP 5 Study will be the largest and most comprehensive evaluation to date of the functional early school age outcomes of children managed with different red blood cell transfusion thresholds during infancy for treatment of anemia of prematurity. This will substantially improve understanding of the longer-term neurological and functional outcomes of different transfusion thresholds; provide more refined evaluation of cognition, executive function, school readiness, motor skills, adaptive functioning, and behavior in former extremely preterm infants; and inform future clinical decision-making for treating anemia of prematurity. Trial registration Clinicaltrials.gov ID: NCT01702805. Primary trial registration 10/05/2012; modified to include follow-up through school age 12/20/2018. This manuscript reflects version 3 of the trial protocol, dated 12/07/2020.
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spelling doaj-art-63c29d2e61394511b0fd2cd1e396f0db2025-08-20T01:51:39ZengBMCBMC Pediatrics1471-24312025-05-0125111310.1186/s12887-025-05732-3The transfusion of prematures early school age follow-up (TOP 5): protocol for a longitudinal cohort studyAmy L. Conrad0Sara B. DeMauro1Haresh Kirpalani2Kristina Ziolkowski3Susan R. Hintz4Betty R. Vohr5Victoria Watson6Tarah T. Colaizy7Edward F. Bell8Jane E. Brumbaugh9Carla M. Bann10Sylvia M. Tan11Jamie E. Newman12Abhik Das13University of IowaChildren’s Hospital of PhiladelphiaChildren’s Hospital of PhiladelphiaChildren’s Hospital of PhiladelphiaStanford University School of MedicineWomen & Infants Hospital of Rhode Island and Warren Alpert Medical School of Brown UniversityWomen & Infants Hospital of Rhode Island and Warren Alpert Medical School of Brown UniversityUniversity of IowaUniversity of IowaMayo Clinic College of Medicine and ScienceAnalytics Division, RTI InternationalAnalytics Division, RTI InternationalAnalytics Division, RTI InternationalAnalytics Division, RTI InternationalAbstract Background Anemia of prematurity is a common concern for extremely low birth weight (ELBW) patients in the neonatal intensive care unit. The hemoglobin threshold at which the benefits of red blood cell transfusion outweigh the risks is unknown. The NICHD Neonatal Research Network Transfusion of Prematures (TOP) Trial evaluated whether higher (more liberal) hemoglobin transfusion thresholds resulted in improved survival without neurodevelopmental impairment at 22–26 months’ corrected age. A total of 1824 ELBW infants born at 22–28 weeks’ gestation were enrolled in the trial and randomized to either a restrictive or liberal set of red blood cell transfusion thresholds. Longer-term impacts of different transfusion thresholds in treatment for anemia of prematurity remain unknown. The Transfusion of Prematures Early School Age Follow-up (TOP 5) Study extends follow-up of all surviving children enrolled in the TOP Trial until early school age. It aims to assess longer-term cognitive and functional effects of differing transfusion thresholds in the newborn period for anemia in this large, multicenter cohort. Methods Parents of surviving trial participants complete telephone questionnaires when their children are 3 and 4 years’ corrected age. A single in-person study visit takes place at early school age (5 years, 0 months to 7 years, 11 months’ corrected age). Children undergo a multidimensional assessment of functional outcomes, and parents complete a battery of questionnaires. Discussion The TOP 5 Study will be the largest and most comprehensive evaluation to date of the functional early school age outcomes of children managed with different red blood cell transfusion thresholds during infancy for treatment of anemia of prematurity. This will substantially improve understanding of the longer-term neurological and functional outcomes of different transfusion thresholds; provide more refined evaluation of cognition, executive function, school readiness, motor skills, adaptive functioning, and behavior in former extremely preterm infants; and inform future clinical decision-making for treating anemia of prematurity. Trial registration Clinicaltrials.gov ID: NCT01702805. Primary trial registration 10/05/2012; modified to include follow-up through school age 12/20/2018. This manuscript reflects version 3 of the trial protocol, dated 12/07/2020.https://doi.org/10.1186/s12887-025-05732-3AnemiaChild behaviorChild developmentTransfusionNeurodevelopmentOutcomes
spellingShingle Amy L. Conrad
Sara B. DeMauro
Haresh Kirpalani
Kristina Ziolkowski
Susan R. Hintz
Betty R. Vohr
Victoria Watson
Tarah T. Colaizy
Edward F. Bell
Jane E. Brumbaugh
Carla M. Bann
Sylvia M. Tan
Jamie E. Newman
Abhik Das
The transfusion of prematures early school age follow-up (TOP 5): protocol for a longitudinal cohort study
BMC Pediatrics
Anemia
Child behavior
Child development
Transfusion
Neurodevelopment
Outcomes
title The transfusion of prematures early school age follow-up (TOP 5): protocol for a longitudinal cohort study
title_full The transfusion of prematures early school age follow-up (TOP 5): protocol for a longitudinal cohort study
title_fullStr The transfusion of prematures early school age follow-up (TOP 5): protocol for a longitudinal cohort study
title_full_unstemmed The transfusion of prematures early school age follow-up (TOP 5): protocol for a longitudinal cohort study
title_short The transfusion of prematures early school age follow-up (TOP 5): protocol for a longitudinal cohort study
title_sort transfusion of prematures early school age follow up top 5 protocol for a longitudinal cohort study
topic Anemia
Child behavior
Child development
Transfusion
Neurodevelopment
Outcomes
url https://doi.org/10.1186/s12887-025-05732-3
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