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Unbound bilirubin and bilirubin-albumin binding levels of Japanese neonates

Abstract

Objective

To determine postnatal changes in total serum bilirubin (TB), unbound bilirubin (UB), and bilirubin-binding affinity of albumin (Ka) among Japanese newborns.

Study design

In a retrospective study, we evaluated for serum TB, UB, and albumin (Alb) levels, and their calculated UB/TB ratios, and Ka in 786 neonates born ≥36 weeks’ gestation and analyzed to subcategories of three postnatal epochs: first, second, and ≥third weeks.

Result

TB levels were significantly higher (p < 0.01) at age ≥three weeks, while UB levels were significantly higher (p < 0.01) in the first week. UB/TB ratios were significantly lower while calculated Ka values were significantly higher as age-in-weeks increased (p < 0.01).

Conclusion

Hyperbilirubinemia in the first and second weeks of age in neonates born ≥36 weeks’ gestation is associated with higher UB levels or UB/TB ratios with lower Ka and may potentially contribute to the risk of developing bilirubin neurotoxicity with aggravated variations in bilirubin, albumin and Ka.

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Fig. 1: Changes in total serum bilirubin (TB) and unbound bilirubin (UB) levels and UB/TB ratios by postnatal age-in-weeks in neonates ≥36 weeks’ gestation.
Fig. 2: Changes in albumin (Alb) levels and calculated Ka values by postnatal age-in-weeks in neonates ≥ 36 weeks’ gestation.
Fig. 3: Correlation between albumin (Alb) levels or calculated Ka values and unbound bilirubin (UB)/ total serum bilirubin (TB) ratios in neonates ≥36 weeks’ gestation.
Fig. 4: Correlation between unbound bilirubin (UB) levels and total serum bilirubin (TB): albumin molar ratios (BAMRs) in neonates ≥ 36 weeks’ gestation.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors sincerely appreciate Dr. Ronald J. Wong (Department of Pediatrics, Stanford University School of Medicine) for his critical review and editing of this manuscript.

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Authors

Contributions

KN: Data curation, formal analysis, original draft preparation. YK: Conceptualization, writing-reviewing and editing, Supervision. YL: Conceptualization, reviewing and editing. All authors approved the final manuscript as submitted.

Corresponding author

Correspondence to Yoshinori Katayama.

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The authors declare no competing interests.

Ethics approval

This study was approved by the ethics committee of Takatsuki General Hospital (approval number: 2021–20) and was performed in accordance with the Declaration of Helsinki.

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The ethics committee of Takatsuki General Hospital approved this observational study with a waiver of informed parental consent.

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Nishizawa, K., Katayama, Y. & Lee, YK. Unbound bilirubin and bilirubin-albumin binding levels of Japanese neonates. J Perinatol 45, 965–970 (2025). https://doi.org/10.1038/s41372-025-02266-5

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