Evaluation of a model for brain bilirubin uptake in jaundiced newborns

A model for brain bilirubin uptake (BBU) predicts that BBU in jaundiced newborns typically depends oil the plasma total bilirubin concentration (TBC) and the bilirubin-albumin dissociation rate constant (k(1)) rather than the unbound bilirubin (B-f). The model's validity was tested by 1) evaluating its requirement that k(3) >>> k(2), where k(3), and k(2), are the rate constants for BBU and B-f-albumin association, respectively, and 2) determining whether the calculated BBU is <= 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, B-f, k(1), and k(2) from 185 jaundiced newborns. Mean k(2) was compared with the reported k3 value of 0.08/s. BBU calculated from TBC and k(1) was expected to be <= 0.005 mu g/kg/s given the reported bilirubin production rate of 0.1 mu g/kg/s. BBU calculated using B, was also compared with the bilirubin production rate. The mean k(2) of 8.9 L/mu mol/s was greater than k(3), and the mean BBU of 0.72 mu g/kg/s exceeded the expected range of <= 0.005 mu g/kg/s. However, mean BBU using B-f (0.00073 mu g/kg/s) was within the expected range. A mathematical model calculating BBU as a function of TBC and k(1) could not be validated. BBU calculated from B-f is consistent with the observation that < 1% of the miscible bilirubin pool is distributed in the brain.