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Changes in bilirubin in infants with hypoxic–ischemic encephalopathy

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Abstract

Antioxidant properties of bilirubin have been reported in many studies. We hypothesized that bilirubin might be involved in neuroprotection mechanisms against oxidative stress in infants with hypoxic–ischemic encephalopathy (HIE) and that total serum bilirubin (TSB) might increase in these patients. We retrospectively studied infants with gestational age ≥ 35 weeks and birth weight ≥ 1800 g who were admitted to the neonatal intensive care unit (NICU) with a diagnosis of moderate-to-severe HIE and received or did not receive therapeutic hypothermia. We evaluated peak TSB and changes of mean TSB in these patients in comparison with a control group of infants admitted to the NICU with diagnoses other than HIE. Peak and mean TSB values were lower in the no hypothermia and hypothermia groups in comparison with the control group, while differences were not noted between infants who received hypothermia or did not. Regression analysis showed that HIE and hypothermia significantly reduced the risk of developing TSB values higher than median value (> 8.4 mg/dL) in our population.

Conclusion: Peak and mean TSB values were lower in infants with moderate-to-severe HIE than in control infants. HIE and hypothermia independently decreased TSB. These results exclude a TSB increase as a neuroprotective mechanism in infants with HIE. We speculated that low TSB values in infants with HIE could be due to hypoxic repression of HO expression and represent a defensive strategy for limiting brain injuries in these patients.

What is Known:

• The role of oxidative stress in the pathophysiology of hypoxic–ischemic encephalopathy (HIE) has been elucidated in many studies, and other studies have demonstrated the antioxidant properties of bilirubin.

• The potential neuroprotective role of bilirubin as antioxidant agent has never been evaluated in infants with HIE.

What is New:

• Mean total serum bilirubin (TSB) values are lower in infants with moderate-to-severe HIE than in control infants, since HIE and hypothermia independently decreased TSB.

• An increase in bilirubin was not a neuroprotective mechanism in infants with HIE possibly because of hypoxic repression of HO expression as defensive strategy for limiting brain injuries.

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Abbreviations

HO:

Heme-oxygenase

HIE:

Hypoxic–ischemic encephalopathy (HIE)

TSB:

Total serum bilirubin

NICU:

Neonatal intensive care unit

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Funding

This study was carried out without specific funding.

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Authors and Affiliations

  1. Division of Neonatology, Careggi University Hospital of Florence, 3 Largo Brambilla, 50141, Florence, Italy

    Carlo Dani, Chiara Poggi, Claudia Fancelli & Simone Pratesi

  2. Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy

    Carlo Dani

Authors
  1. Carlo Dani
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  2. Chiara Poggi
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  3. Claudia Fancelli
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  4. Simone Pratesi
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Contributions

CD designed the study, supervised data collection, carried out the analyses, drafted the manuscript, and approved the final manuscript as submitted. CP, CD, and SP performed the data collection, participated in data analysis, reviewed and revised the manuscript, and approved the final manuscript as submitted.

Corresponding author

Correspondence to Carlo Dani.

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Authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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Communicated by Patrick Van Reempts

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Dani, C., Poggi, C., Fancelli, C. et al. Changes in bilirubin in infants with hypoxic–ischemic encephalopathy. Eur J Pediatr 177, 1795–1801 (2018). https://doi.org/10.1007/s00431-018-3245-4

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  • DOI: https://doi.org/10.1007/s00431-018-3245-4

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