Assessment of the clinical significance of a UGT1A1 gene variant in affecting phototherapy response and long-term outcomes in neonatal hyperbilirubinemia.

Abstract

Objective: Phototherapy is the standard treatment, but its efficacy can vary among neonates, prompting interest in genetic factors, particularly UGT1A1 gene variants. This study aims to evaluate the clinical significance of the UGT1A1 gene variant in influencing phototherapy response and long-term outcomes in neonatal hyperbilirubinemia.

Methods: This retrospective study included 104 neonates with neonatal hyperbilirubinemia, of whom 63 carried the normal UGT1A1 gene, and 41 had the homozygous UGT1A1 Gly71Arg variant. Genetic testing for the UGT1A1 gene Gly71Arg locus had been previously conducted as part of their clinical care using DNA extraction and sequencing. Parameters such as phototherapy duration, complications, and long-term outcomes were analyzed to assess the correlation between the UGT1A1 gene variant and clinical results. Furthermore, the impact of the UGT1A1 gene variant was evaluated using receiver operating characteristic (ROC) curve analysis.

Results: Neonates with the UGT1A1 gene variant showed prolonged phototherapy duration, extended time to bilirubin normalization, increased phototherapy complications, higher phototherapy intensity, and more excellent rehospitalization rates for hyperbilirubinemia. The presence of the UGT1A1 gene variant correlated with specific complications, including dehydration, hypoglycemia, and hyperbilirubinemia. Additionally, infants with the UGT1A1 gene variant had significantly higher rates of developmental delay, cerebral palsy, hearing impairment, neurodevelopmental disorders, and severe hyperbilirubinemia-related morbidities. Mean peak bilirubin levels were significantly higher in the variant compared with the normal group. ROC analysis demonstrated moderate to strong sensitivities and specificities with area under the curve (AUC) values ranging from 0.693 to 0.830.

Conclusion: We found that a UGT1A1 gene variant significantly affects phototherapy response and can impact long-term outcomes in neonatal hyperbilirubinemia, highlighting the potential of genetic testing for personalized risk assessment and management of hyperbilirubinemia in newborns.