The bilirubin albumin ratio in the management of hyperbilirubinemia in preterm infants to improve neurodevelopmental outcome: a randomized controlled trial--BARTrial.

Christian V Hulzebos,Djien Liem,Karen K M Korbeeck-Van Hof,Enrico Lopriore,Martin Offringa,Ineke Van Vliet,Peter H Dijk,Aleid G Van Wassenaer-Leemhuis,Debbie H G M Nuytemans,Jan Buijs,Paul Govaert,Arend F Bos,Richard A Van Lingen,Cecile Wolfs,Deirdre E Van Imhoff,Koen N J A Van Braeckel,E.h Quik ,Twan Mulder ,Liesbeth J.m Groot Jebbink ,Selma Ruiter ,Paul F M Krabbe ,Petri Mansvelt,Letty Van Toledo-Eppinga,Manon J N L Benders ,W P F Fetter ,Céleste R Laarman

doi:10.1371/journal.pone.0099466

Abstract

Background and ObjectiveHigh bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity. The B/A ratio may be a valuable measure, in addition to the total serum bilirubin (TSB), in the management of hyperbilirubinemia. We aimed to assess whether the additional use of B/A ratios in the management of hyperbilirubinemia in preterm infants improved neurodevelopmental outcome.MethodsIn a prospective, randomized controlled trial, 615 preterm infants of 32 weeks' gestation or less were randomly assigned to treatment based on either B/A ratio and TSB thresholds (consensus-based), whichever threshold was crossed first, or on the TSB thresholds only. The primary outcome was neurodevelopment at 18 to 24 months' corrected age as assessed with the Bayley Scales of Infant Development III by investigators unaware of treatment allocation. Secondary outcomes included complications of preterm birth and death.ResultsComposite motor (100±13 vs. 101±12) and cognitive (101±12 vs. 101±11) scores did not differ between the B/A ratio and TSB groups. Demographic characteristics, maximal TSB levels, B/A ratios, and other secondary outcomes were similar. The rates of death and/or severe neurodevelopmental impairment for the B/A ratio versus TSB groups were 15.4% versus 15.5% (P = 1.0) and 2.8% versus 1.4% (P = 0.62) for birth weights ≤1000 g and 1.8% versus 5.8% (P = 0.03) and 4.1% versus 2.0% (P = 0.26) for birth weights of >1000 g.ConclusionsThe additional use of B/A ratio in the management of hyperbilirubinemia in preterm infants did not improve their neurodevelopmental outcome.Trial RegistrationControlled-Trials.com ISRCTN74465643

Highlights

Background and ObjectiveHigh bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity
The B/A ratio and total serum bilirubin (TSB) groups were similar with regards to the baseline characteristics (Table 1)
The additional use of the B/A ratio did not reduce the rate of neurodevelopmental impairment (NDI), severe or otherwise

Summary

Introduction

High bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity. The total bilirubin load together with Bf is thought to predict bilirubin neurotoxicity more reliably than the total serum bilirubin (TSB), as assessed by clinical and electrophysiological parameters, i.e. neurodevelopmental outcome and maturation of automated brain stem responses, respectively. The bilirubin (TSB)/albumin (B/A) ratio, which could be a surrogate for Bf, might be a good additional parameter to TSB, to indicate an increased risk of bilirubin-induced neurotoxicity in preterm infants. Mainly retrospective data have favored an additional role for high B/A ratios as risk factors for bilirubin-induced neurotoxicity and only limited data exist regarding B/A ratios in the management and neurodevelopmental outcome of preterm infants with unconjugated hyperbilirubinemia. Mainly retrospective data have favored an additional role for high B/A ratios as risk factors for bilirubin-induced neurotoxicity and only limited data exist regarding B/A ratios in the management and neurodevelopmental outcome of preterm infants with unconjugated hyperbilirubinemia. [5] What is lacking are prospective clinical trials on the use of the B/A ratio in jaundiced preterm infants to evaluate its safety and clinical utility in preventing or reducing long-term bilirubin-induced neurotoxicity.

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