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  • Clinical Research Article
  • Published:

Bilirubin isomers during LED phototherapy of hyperbilirubinemic neonates, blue–green (~478 nm) vs blue

Pediatric Research volume 97, pages 1623–1628 (2025)Cite this article

Abstract

Background

The clinical part of this randomized controlled trial concerning phototherapy of neonates with hyperbilirubinemia showed that the recommended blue–green LED light (≈478 nm) was 31% more efficient than standard blue LED light (≈459 nm) measured by the decline in total serum bilirubin. Lumirubin has biologic effects. The aim was to compare the serum bilirubin isomers, efficacy, and biologic effects between the two phototherapy groups.

Methods

Inclusion criteria: neonates healthy except for hyperbilirubinemia, gestational age ≥33 weeks, birth weight ≥1800 g, and postnatal age >24 h. Forty-two neonates were randomized to receive overhead blue–green light and 44 blue light. Treatment 24 h. The light irradiance was equal.

Results

The percentage decrease of combined bilirubin isomers was 47.8% for blue–green light vs 33.4% for blue light, the ratio being 1.43. Corresponding values for Z,Z-bilirubin were 55.6% vs 44.2%, the ratio being 1.26. The increase in the absolute serum concentrations of the photoisomer Z,E-bilirubin and thereby combined photoisomers were greater using blue light.

Conclusion

Blue–green light was essentially more efficient determined by the decline of combined bilirubin isomers and Z,Z-bilirubin itself. Regarding biological effects neonates receiving blue–green light might be more affected than neonates receiving blue light.

Impact

  • Phototherapy of hyperbilirubinemic neonates using blue–green LED light with a peak emission of 478 nm was 43% more efficient than standard blue LED light with a peak emission of 459 nm was measured by the decline of serum combined bilirubin isomers, and the decline of toxic Z,Z-bilirubin was 26% greater.

  • Apparently, there was a discrepancy between the huge drop in total serum bilirubin and the low serum concentrations of E,Z-bilirubin and E,Z-lumirubin. This was caused by the rapid excretion of E,Z-lumirubin.

  • Lumirubin has biologic effects. Due to greater lumirubin production neonates exposed to blue–green light might be more affected than those exposed to blue light.

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Fig. 1: Formation of bilirubin isomers during phototherapy of hyperbilirubinemic neonates.
Fig. 2: A HPLC chromatogram showing the separation of the bilirubin isomers after 24 h of treatment.

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Data availability

The materials described in the manuscript, including all the raw data, will be freely available to any researcher wishing to use them for non-commercial purposes, without breaching participant confidentiality.

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Acknowledgements

We thank physicians and nurses for their collaboration and enthusiasm for carrying out the study. We thank Hendrik J. Vreman and Thor Willy Ruud Hansen for an exhaustive and excellent review of the manuscript and for giving valuable advice for the improvement of the manuscript. Further, Hendrik J. Vreman is thanked for producing the phototherapy devices and performing the measurements of the light irradiance.

Funding

None of the authors have any financial support to disclose.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Aalborg University Hospital, Aalborg, Denmark

    Finn Ebbesen

  2. Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark

    Finn Ebbesen & Mette L. Donneborg

  3. Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

    Poul H. Madsen

  4. Unit of Psychiatric Research, Psychiatry, Aalborg University Hospital, Aalborg, Denmark

    Maria Rodrigo-Domingo

  5. Department of Pediatrics, The North Denmark Regional Hospital, Hjoerring, Denmark

    Mette L. Donneborg

  6. Centre for Clinical Research, The North Denmark Regional Hospital, Hjoerring, Denmark

    Mette L. Donneborg

Authors
  1. Finn Ebbesen
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  2. Poul H. Madsen
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  3. Maria Rodrigo-Domingo
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  4. Mette L. Donneborg
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Contributions

F.E. conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. P.H.M. performed the biochemical analyses, and reviewed and revised the manuscript. M.R.-D. performed the statistical analyses, and reviewed and revised the manuscript. M.L.D. conceptualized and designed the study, collected the data, and reviewed and revised the manuscript. All authors approved the final version to be published.

Corresponding author

Correspondence to Finn Ebbesen.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

Verbal and written informed consent was obtained from the parents. All regulations concerning research, at the time the studies were conducted, were followed. The trial was approved by the Committee for Biomedical Research Ethics in the North Denmark Region, N-20160071, and registered in the Clinical Trial Registry number NCT 03183986.

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Ebbesen, F., Madsen, P.H., Rodrigo-Domingo, M. et al. Bilirubin isomers during LED phototherapy of hyperbilirubinemic neonates, blue–green (~478 nm) vs blue. Pediatr Res 97, 1623–1628 (2025). https://doi.org/10.1038/s41390-024-03493-w

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