This study aimed to investigate the association between serum high-sensitivity cardiac troponin I (hs-cTnI) concentrations, platelet counts, and the severity of neonatal hyperbilirubinemia (NHB), as well as their correlation with the total bilirubin/albumin (B/A) ratio. A total of 82 neonates diagnosed with NHB and treated at JingMen People's Hospital of Hubei Province, China, between September 2023 and December 2023 were enrolled. Participants were categorized into mild and severe NHB groups based on total bilirubin levels. Serum hs-cTnI concentrations, platelet counts, and total bile acid levels were compared between groups. Correlations among hs-cTnI, platelet counts, and the B/A ratio were assessed. Neonates in the severe NHB group exhibited significantly higher hs-cTnI concentrations (median 64.1 [31.7, 92.1] ng/mL) compared with those in the mild NHB group (median 41.9 [17.55, 60.4] ng/mL; p=0.015). The B/A ratio was also significantly higher in the severe group (10.5 [10.0, 10.9] vs. 8.4 [7.9, 8.9]; p<0.001). No significant differences were observed between groups regarding platelet counts or total bile acid levels. Additionally, neither platelet count nor the B/A ratio demonstrated a significant correlation with hs-cTnI concentrations. Neonates with severe hyperbilirubinemia exhibited significantly elevated hs-cTnI concentrations and B/A ratios. However, hs-cTnI levels were not significantly influenced by platelet counts or the B/A ratio.

• MeSH
• Bilirubin * blood   MeSH
• Biomarkers blood   MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Hyperbilirubinemia, Neonatal * blood   diagnosis   MeSH
• Platelet Count methods   MeSH
• Serum Albumin * analysis   metabolism   MeSH
• Severity of Illness Index MeSH
• Troponin I * blood   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• China MeSH
• Names of Substances
• Bilirubin * MeSH
• Biomarkers MeSH
• Serum Albumin * MeSH
• Troponin I * MeSH

Kernicterus spectrum disorder is the permanent and highly disabling neurologic sequel of neonatal exposure to hyperbilirubinemia, presenting, among other symptoms, variable and untreatable motor disabilities. To search for potential biomolecular explanations, we used a Gunn rat colony exhibiting spontaneous hyperbilirubinemia and a large variability of motor deficits on a beam-walking test. Histological and microscopic analyses confirmed worsening damage in the cerebellum (Cll; hypoplasia, increased death of neurons, and disrupted astroglial structures) and parietal motor cortex (hCtx; increased cell sufferance and astrogliosis). Clustering and network analyses of transcriptomic data reveal rearrangement of the physiological expression patterns and signaling pathways associated with bilirubin neurotoxicity. Bilirubin content among hyperbilirubinemic (jj) animals is overlapped, which suggests that the amount of bilirubin challenge does not fully explain the tissue, transcriptomic, proteomic, and neurobehavioral alterations. The expression of nine genes involved in key postnatal brain development processes is permanently altered in a phenotype-dependent manner. Among them, Grm1, a metabotropic glutamatergic receptor involved in glutamate neurotoxicity, is consistently downregulated in both brain regions both at the transcriptomic and proteomic levels. Our results support the role of Grm1 and glutamate as biomolecular markers of ongoing bilirubin neurotoxicity, suggesting the possibility to improve diagnosis by 1H-MR spectroscopy.

• Keywords
• Grm1, Gunn rats, PKC3, calcium, dystonia, gene clustering, glutamate receptors, kernicterus spectrum disorder, neonatal jaundice, neurotoxicity,
• MeSH
• Bilirubin metabolism   MeSH
• Phenotype MeSH
• Kernicterus metabolism   genetics   MeSH
• Rats MeSH
• Disease Models, Animal MeSH
• Brain * metabolism   pathology   MeSH
• Animals, Newborn MeSH
• Hyperbilirubinemia, Neonatal * metabolism   genetics   pathology   MeSH
• Rats, Gunn MeSH
• Proteome * metabolism   MeSH
• Proteomics methods   MeSH
• Gene Expression Profiling MeSH
• Transcriptome * MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Bilirubin MeSH
• Proteome * MeSH