Evaluation of a model for brain bilirubin uptake in jaundiced newborns

Abstract

A model for brain bilirubin uptake (BBU) predicts that BBU in jaundiced newborns typically depends on the plasma total bilirubin concentration (TBC) and the bilirubin-albumin dissociation rate constant (k1) rather than the unbound bilirubin (Bf). The model's validity was tested by 1) evaluating its requirement that k3>>>k2, where k3 and k2 are the rate constants for BBU and Bf-albumin association, respectively, and 2) determining whether the calculated BBU is <or=5% of the bilirubin production rate, the approximate BBU expected if brain bilirubin levels are <1% of the miscible bilirubin pool as reported in the literature. The model was investigated using peroxidase test measurements of TBC, Bf, k1, and k2 from 185 jaundiced newborns. Mean k2 was compared with the reported k3 value of 0.08/s. BBU calculated from TBC and k1 was expected to be <or=0.005 microg/kg/s given the reported bilirubin production rate of 0.1 microg/kg/s. BBU calculated using Bf was also compared with the bilirubin production rate. The mean k2 of 8.9 L/micromol/s was greater than k3, and the mean BBU of 0.72 microg/kg/s exceeded the expected range of <or=0.005 microg/kg/s. However, mean BBU using Bf (0.00073 microg/kg/s) was within the expected range. A mathematical model calculating BBU as a function of TBC and k1 could not be validated. BBU calculated from Bf is consistent with the observation that <1% of the miscible bilirubin pool is distributed in the brain.