Bilirubin-Induced Neurologic Damage — Mechanisms and Management Approaches

Watchko, Jon F.; Tiribelli, Claudio

doi:10.1056/nejmra1308124

Cited by 289 publications

(218 citation statements)

References 67 publications

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“…A low Alb level and a high bilirubin/Alb ratio are recommended risk factors for BIND in recognition that binding status is a concern in the management of newborn jaundice (2,(6)(7)(8). However, the variation in the BBC/Alb among infants has been pointed out as the reason for caution in the use of the Alb level and bilirubin/Alb molar ratio as quantitative indicators of binding status in BIND risk assessment (2,4,(6)(7)(8). Thus, a direct measure of BBC should be advantageous.…”

Section: Discussionmentioning

confidence: 99%

“…B ilirubin binding capacity (BBC) is a determinative measure of a neonate's ability to cope with an excessive bilirubin load (e.g., due to increased bilirubin production from hemolysis) that may be impacted by a variety of biologic factors, including disordered or insufficient bilirubin binding to albumin (Alb) (1,2). The long-standing belief that total serum/ plasma bilirubin (TB), by itself, does not reliably predict an infant's risk for developing bilirubin-induced neurological dysfunction (BIND) or kernicterus has been recently reconfirmed (2)(3)(4)(5).…”

mentioning

confidence: 99%

“…The long-standing belief that total serum/ plasma bilirubin (TB), by itself, does not reliably predict an infant's risk for developing bilirubin-induced neurological dysfunction (BIND) or kernicterus has been recently reconfirmed (2)(3)(4)(5). The traditional reliance on the TB level alone as a clinical measure of both bilirubin exposure and risk for neurotoxicity may result in overuse of phototherapy or delayed phototherapy in cases where exposure risk is underestimated.…”

mentioning

confidence: 99%

“…It is recommended to use risk factors, including prematurity, hemolysis, sepsis, acidosis, and hypoalbuminemia, to modulate assessment of risk of neurotoxicity at TB levels adjusted for age-in-hours (2,(6)(7)(8). However, neither serum Alb levels nor the molar ratio of TB to Alb has been predictive of bilirubin neurotoxicity (4,(6)(7)(8).…”

mentioning

confidence: 99%

“…While an assay of serum/plasma unbound or "free" bilirubin (UB) to predict the risk of BIND has been employed for many years by researchers (8), it generally remains a research tool. The role of UB as a unique clinical biomarker of BIND has not been fully elucidated (2,4,8). However, sufficient bench data has accumulated to suggest that dynamic UB is "buffered" by an infant's BBC (4).…”

mentioning

confidence: 99%

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Neonatal bilirubin binding capacity discerns risk of neurological dysfunction

Lamola

Bhutani

et al. 2014

Pediatr Res

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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 bilirubininduced 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.B ilirubin binding capacity (BBC) is a determinative measure of a neonate's ability to cope with an excessive bilirubin load (e.g., due to increased bilirubin production from hemolysis) that may be impacted by a variety of biologic factors, including disordered or insufficient bilirubin binding to albumin (Alb) (1,2). The long-standing belief that total serum/ plasma bilirubin (TB), by itself, does not reliably predict an infant's risk for developing bilirubin-induced neurological dysfunction (BIND) or kernicterus has been recently reconfirmed (2-5). The traditional reliance on the TB level alone as a clinical measure of both bilirubin exposure and risk for neurotoxicity may result in overuse of phototherapy or delayed phototherapy in cases where exposure risk is underestimated.It is recommended to use risk factors, including prematurity, hemolysis, sepsis, acidosis, and hypoalbuminemia, to modulate assessment of risk of neurotoxicity at TB levels adjusted for age-in-hours (2,6-8). However, neither serum Alb levels nor the molar ratio of TB to Alb has been predictive of bilirubin neurotoxicity (4,6-8). BBC, when directly measured by various methods, is generally lower than that expected from the Alb level, especially in preterm and sick infants in whom the ratio of capacity to Alb is highly variable (9,10). Thus, the Alb level is only a rough estimate of an infant's BBC. The neuroprotective role of serum Alb, the bilirubin transport protein, was demonstrated in vitro years ago (11). Seminal demonstration that the antibiotic sulfisoxazole was the cause of acute bilirubin encephalopathy even at low TB values highlig...

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