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Published on: November 20, 2015
Neonatal bilirubin binding capacity discerns risk of neurological dysfunction
Angelo A Lamola1, Vinod K Bhutani1, Lizhong Du2
1Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Stanford, California.
Insights
Bilirubin binding capacity (BBC) assays in neonates offer a more robust method for assessing neurotoxicity risk than total bilirubin and gestational age alone. Individualized BBC testing can better predict infant tolerance to bilirubin loads.
Area of Science:
- Neonatal Medicine
- Biochemistry
Background:
- Bilirubin binding capacity (BBC) reflects an infant's ability to handle free bilirubin.
- BBC is distinct from albumin levels due to complex confounding factors.
Purpose of the Study:
- To directly assay BBC in neonates using a modified hematofluorometric method.
- To determine if BBC combined with total bilirubin (TB) can assess neurotoxicity risk.
Main Methods:
- A novel hematofluorometric method was used to measure BBC in whole blood from neonates.
- Data were combined with an archived database, and multiple regression modeling was applied.
Main Results:
- Total bilirubin (TB) ranged from 0.7-22.8 mg/dl and BBC from 6.3-47.5 mg/dl.
- Gestational age (GA) correlated with BBC (r = 0.54; P < 0.0002).
- Recommended TB thresholds for treatment correspond to 45% and 67% of the observed BBC regression line.
Conclusions:
- The variability in BBC levels suggests individualized assays are superior for gauging bilirubin neurotoxicity risk.
- BBC offers a more robust assessment compared to TB and GA alone.
Background:
Bilirubin binding capacity (BBC) defines the dynamic relationship between an infant's level of unbound or "free" bilirubin and his/her ability to "tolerate" increasing bilirubin loads. BBC is not synonymous with albumin (Alb) levels because Alb binding of bilirubin is confounded by a variety of molecular, biologic, and metabolic factors.
Methods:
We utilized a novel modification of a previously developed hematofluorometric method to directly assay BBC in whole blood from preterm and term neonates and then combined these data with an archived database. Total bilirubin (TB) was also measured, and multiple regression modeling was used to determine whether BBC in combination with TB measurements can assess an infant's risk for developing bilirubin-induced neurotoxicity.
Results:
TB and BBC levels ranged from 0.7-22.8 to 6.3-47.5 mg/dl, respectively. Gestational age (GA) correlated with BBC (r = 0.54; P < 0.0002) with a slope of 0.93 mg/dl/wk by logistic regression. Our calculations demonstrate that recently recommended GA-modulated TB thresholds for phototherapy and exchange transfusion correspond to 45 and 67% saturation of our observed regression line, respectively.
Conclusion:
We speculate that the spread of BBC levels around the regression line (± 5.8 mg/dl) suggests that individualized BBC assays would provide a robust approach to gauge risk of bilirubin neurotoxicity compared with TB and GA.
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