To evaluate the association between UGT1A1 variants identified through newborn genetic screening and the development of clinically significant neonatal hyperbilirubinemia.
Approach:
Grouping: Newborns with confirmed biallelic or multi-allelic UGT1A1 variants were categorized into homozygous (Hom), compound heterozygous (CH), or three-loci (3 loci) groups, with the most frequent variants being c.211G>A and c.-41_-40dup.
Key Findings:
Seventy-five newborns had confirmed biallelic or multi-allelic UGT1A1 variants (Hom, n = 45; CH, n = 26; 3 loci, n = 4).
TcB levels were higher in mutation groups compared to controls on day 42 (P < 0.001).
Clinically significant neonatal hyperbilirubinemia was rare, with only four cases identified (3/75 in the mutation group and 1/40 in controls; P = 0.367).
Interpretation:
Common UGT1A1 variants were associated with mildly elevated TcB levels at 6 weeks, suggesting slower postnatal bilirubin clearance, but showed little association with clinically significant hyperbilirubinemia.
Limitations:
The small number of clinically significant hyperbilirubinemia events limits firm conclusions.
Detailed data on non-genetic contributors to hyperbilirubinemia were not uniformly available.
Conclusion:
The findings support a variant-level reporting strategy for newborn genetic screening.
