Gilbert's syndrome is a contributory factor in prolonged unconjugated hyperbilirubinemia of the newborn

Objective: Prolonged neonatal jaundice, beyond day 14 of life, is very comm on and of concern to the clinician. The aim of this study was to investigat e whether a genetic mutation in the bilirubin UGT1A1 gene, which has been a ssociated with Gilbert's syndrome in adults, is a contributory factor in pr olonged neonatal jaundice. Study design: Blood was collected from 85 term newborns with unexplained hy perbilirubinemia, and DNA was prepared. The neonates were divided into 6 gr oups depending on whether they were breast-fed or bottle-fed and whether th ey had acute, prolonged, or very prolonged jaundice. UGT1A1 TATA promoter g enotyping (DNA test for Gilbert's syndrome) was performed on all samples, a nd analysis of the entire UGT1A1 coding sequence was performed in a represe ntative sample (11 of 26) of very prolonged cases. Results: In addition to the known common UGT1A1 TATA alleles (TA6 and TA7), a novel TATA allele (TA5) in a neonate with very prolonged jaundice was id entified. Statistical analysis of the TATA genotype distributions within th e group of breast-fed neonates revealed significant differences among the a cute, prolonged, and very prolonged subgroups (.05 > P > .01): the incidenc e of familial hyperbilirubinemia genotypes (7/7 and 5/7) is 5 times greater in very prolonged cases (31%) relative to acute cases (6%). Neonates with prolonged jaundice from family pedigrees were observed to demonstrate the G ilbert's phenotype as children or young adults. Conclusions: A genetic predisposition to develop prolonged neonatal hyperbi lirubinemia in breast-fed infants is associated with TATA box polymorphism of the UGT1A1 gene and will be recognized as Gilbert's syndrome in adulthoo d.