657 - Evidence for change in management for mixed neonatal hyperbilirubinemia

Publication Number: 657.5014

Jonathan A. Berken, The Children's Hospital of Philadelphia, Philadelphia, PA, United States; Jonathan A. Berken, The Children's Hospital of Philadelphia, Philadelphia, PA, United States; Kirsten Craddock, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Sonika Agarwal, The Children's Hospital of Philadelphia, Philadelphia, PA, United States; Elizabeth Rand, Children's Hospital of Philadelphia, Philadelphia, PA, United States; Heather M. French, Children's Hospital of Philadelphia, Philadelphia, PA, United States

Background: Unconjugated hyperbilirubinemia is a prevalent condition in neonates, often leading to interventions such as phototherapy and double-volume exchange transfusion (DVET) to prevent bilirubin-induced neurological damage (BIND) and kernicterus. Current management guidelines use total serum bilirubin (TSB) levels rather than distinguishing between conjugated (CB) and unconjugated bilirubin (UCB). While UCB is neurotoxic, CB is not, often signaling liver pathology rather than posing direct neurotoxic risk.

Objective: This study critically reexamines the need for aggressive interventions, such as phototherapy and DVET, in cases of hyperbilirubinemia driven by elevated CB levels. By reviewing existing literature and institutional data, we question the validity of applying treatments designed for UCB to cases dominated by CB. Furthermore, we emphasize the need for more precise diagnostic approaches to identify liver-specific causes of hyperbilirubinemia, aiming to reduce unnecessary interventions, improve clinical outcomes, and mitigate medicolegal risks.

Design/Methods: We analyzed admission data from the Neonatal/Infant Intensive Care Unit at the Children’s Hospital of Philadelphia from 2017 to 2023, focusing on cases of kernicterus identified through ICD10 coding. We examined bilirubin fractionation in these cases and assessed the clinical outcomes associated with elevated CB levels. Additionally, we reviewed cases of conjugated hyperbilirubinemia from 2015 to 2023 to further investigate the relationship between bilirubin type and neurotoxicity.

Results: Of 8,957 infants admitted, 4,821 exhibited increased total serum bilirubin (TSB), with 2,334 receiving phototherapy. Only 5 cases of kernicterus were identified, all associated with elevated UCB levels; no kernicterus cases were linked to isolated or predominantly elevated CB. From 2015 to 2023, among 136 neonates with conjugated hyperbilirubinemia, only 2 developed kernicterus, both characterized by significantly elevated UCB levels (Table 1).

Conclusion(s): These findings indicate that hyperbilirubinemia driven primarily by elevated CB does not contribute to kernicterus, challenging current treatment guidelines that rely solely on TSB levels. We recommend that future hyperbilirubinemia management protocols incorporate bilirubin fractionation to avoid unnecessary interventions for elevated CB, thereby optimizing neonatal care and minimizing risks associated with aggressive treatments (Figure 1). This reassessment may pave the way for more tailored and effective management strategies for hyperbilirubinemia in neonates.

Jonathan Berken Resume
Jonathan Berken_CV_October 2024 (1).pdf

Management Flowchart for Hyperbilirubinemia with Bilirubin Fractionation.
Berken_Bilirubin_Figure 1.pdfThis flowchart outlines a clinical decision-making pathway for the assessment and management of hyperbilirubinemia. The process begins with evaluating total bilirubin levels, followed by fractionation into unconjugated and conjugated forms. Unconjugated hyperbilirubinemia is managed with phototherapy for mild cases, while more severe cases may require double volume exchange transfusion. Conjugated hyperbilirubinemia prompts investigation into underlying causes such as liver dysfunction or cholestasis, followed by targeted treatment. The color-coded steps indicate different stages of the diagnostic and therapeutic process, aiding in the structured management of hyperbilirubinemia.