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

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.

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.

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.

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.