The Bilirubin Albumin Ratio in the Management of Hyperbilirubinemia in Preterm Infants to Improve Neurodevelopmental Outcome: A Randomized Controlled Trial – BARTrial

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

The role of bilirubin to albumin ratio as a predictor for mortality in critically ill patients without existing liver or biliary tract disease

“…In the previous reports, serum B/A ratio was expected as a predictor of bilirubin encephalopathy and neurologic dysfunction in neonates [12,29,30]. Free bilirubin, that is not bound to albumin, can pass by the blood-brain-barrier and appear a neurotoxicity [12,29,30]. The B/A ratio, which can be a substitute for free bilirubin, is considered to be a good additional parameter for total serum bilirubin, indicating an higher risk of bilirubininduced neurotoxicity in preterm infants [12,29,30].…”

“…In this study, we analyzed B/A ratio for predictor of mortality. In the previous reports, serum B/A ratio was expected as a predictor of bilirubin encephalopathy and neurologic dysfunction in neonates [12,29,30]. Free bilirubin, that is not bound to albumin, can pass by the blood-brain-barrier and appear a neurotoxicity [12,29,30].…”

“…Free bilirubin, that is not bound to albumin, can pass by the blood-brain-barrier and appear a neurotoxicity [12,29,30]. The B/A ratio, which can be a substitute for free bilirubin, is considered to be a good additional parameter for total serum bilirubin, indicating an higher risk of bilirubininduced neurotoxicity in preterm infants [12,29,30]. However, the role of B/A ratio as a predictor for mortality in critically ill patient has not been evaluated before.…”

Movement disorders due to bilirubin toxicity

“…Furthermore, the BAMR was demonstrated to be more correlated with psychomotor outcome at four years compared to other measures of bilirubin [4]. However, another recent study by Hulzebos et al [13] found that clinical use of BAMR, instead of TB thresholds, had no effect on neurodevelopmental outcome at 18–24 months of age [13]. …”

Bilirubin Binding Capacity in the Preterm Neonate

“…However, in a subgroup analysis of infants with >1000 g, the use of BAMR, in addition to TB, was associated with reduction in mortality compared to TB alone. [97] Furthermore, a recent case series of 5 sick premature infants who developed MRI findings of kernicterus with peak TB concentrations ranging from 8.7 to 11.9 mg/dL and serum albumin concentrations ranging from 1.4 to 2.1 g/dL (BAMR >0.47) underscores the importance of measurement of serum albumin in premature infants. [98]…”