Bilirubin Binding Capacity in the Preterm Neonate

Abstract

SYNOPSIS Total serum/plasma bilirubin (TB), the biochemical measure currently used to evaluate and manage hyperbilirubinemia, is not a useful predictor of bilirubin-induced neurotoxicity in premature infants. Altered bilirubin-albumin binding in premature infants limits the usefulness of TB in premature infants. In this article, bilirubin-albumin binding, a modifying factor for bilirubin-induced neurotoxicity, in premature infants is reviewed.

Chronic Auditory Toxicity in Late Preterm and Term Infants With Significant Hyperbilirubinemia

“…In neonates with a BAMR <1 (n = 82), the calculated bilirubinalbumin equilibrium dissociation constant, a measure of the weakness of bilirubin-albumin binding, was similar between the 2 groups (Table 2). 15,16 In regression analyses in which we used 3 separate regression models with mode of delivery, sepsis, and ET included as covariates, there was a significant association of peak UB (but not peak TSB or peak BAMR) with chronic auditory toxicity (Table 2). For each unit (micrograms per deciliter) increase in UB, the odds of having chronic auditory toxicity increased by a factor of 2.41.…”

“…Besides, UB concentration is a better vascular gauge of jaundice severity because it is influenced by and increases with an increase in bilirubin load, a decrease in bilirubin binding capacity, and/or an increase in bilirubin binding dissociation equilibrium constant. 15,16 The slight overlap in UB level between infants with and without chronic auditory toxicity suggests that other unknown clinical factors such as neuronal predisposition to bilirubin toxicity may have a role in pathogenesis. We found no association of clinical risk factors (such as GA, sex, and hemolytic disorders) with chronic auditory toxicity.…”

Amount of Cycloserine Emanating from Terizidone Metabolism and Relationship with Hepatic Function in Patients with Drug-Resistant Tuberculosis

“…The strength of unconjugated bilirubin binding to albumin was calculated according to Eq. (5) [24]:where K af is the binding affinity, with the units L/µmol, and TB and UB are total bilirubin and unconjugated bilirubin, respectively. The AST/ALT ratio [25], a marker reflecting alterations in hepatic function, was calculated by dividing the AST value by the ALT value for each patient.…”

Bilirubin Albumin Binding and Unbound Unconjugated Hyperbilirubinemia in Premature Infants

“…During the first postnatal week, premature infants are at increased risk of bilirubin-induced neurotoxicity at lower concentrations of total serum bilirubin (TSB) than term infants. (1, 2) The increased risk for bilirubin-induced neurotoxicity is due to increased susceptibility of premature neuronal cells to bilirubin injury when unbound bilirubin (UB, bilirubin not bound to protein) (3–5), but not bilirubin bound to albumin, crosses the intact blood brain barrier and the neuronal cell membrane. (6) The critical role of UB in the pathogenesis of bilirubin-induced neurotoxicity has been corroborated by several studies demonstrating that peak UB is a better predictor of abnormal neurological outcomes than TSB in premature and term infants.…”

“…Serum or plasma UB concentrations depend on TSB concentrations, the bilirubin:albumin molar ratio (BAMR, a measure of bilirubin binding capacity of albumin), and the bilirubin-albumin binding affinity (Ka, strength of bilirubin binding to albumin). (3) Although serum albumin levels and bilirubin binding capacities are lower in preterm compared with term infants, there is little information on bilirubin-albumin binding during the first postnatal week as a function of gestational age (GA). (13, 15–17) More importantly, little is known about the primary underlying mechanism for unbound unconjugated hyperbilirubinemia as a function GA in premature infants.…”