title: Extreme neonatal hyperbilirubinemia and a specific genotype: a population-based case-control study.
abstract: OBJECTIVE
  Extreme hyperbilirubinemia (plasma bilirubin ≥ 24.5 mg/dL) is an important risk factor for severe bilirubin encephalopathy. Several risk factors for hyperbilirubinemia are known, but in a large number of patients, a causal factor is never established. UGT1A1 is the rate-limiting enzyme in bilirubin's metabolism. The genotype of Gilbert syndrome, the UGT1A1*28 allele, causes markedly reduced activity of this enzyme, but its association with neonatal hyperbilirubinemia is uncertain and its relationship with extreme hyperbilirubinemia has not been studied. We examined whether the UGT1A1*28 allele is associated with extreme hyperbilirubinemia.
  
  
  METHODS
  The UGT1A1*28 allele was assessed in a case-control study of 231 white infants who had extreme hyperbilirubinemia in Denmark from 2000 to 2007 and 432 white controls. Cases were identified in the Danish Extreme Hyperbilirubinemia Database that covers the entire population. Genotypes were obtained through the Danish Neonatal Screening Biobank. Subgroup analysis was done for AB0 incompatible cases.
  
  
  RESULTS
  No association was found between the UGT1A1*28 allele and extreme hyperbilirubinemia. With the common genotype as reference, the odds ratio of extreme hyperbilirubinemia was 0.87 (range, 0.68-1.13) for UGT1A1*28 heterozygotes and 0.77 (range, 0.46-1.27) for homozygotes. Also, no association was found for AB0 incompatible cases.
  
  
  CONCLUSIONS
  The UGT1A1*28 allele was not associated with risk for extreme hyperbilirubinemia in this study.
authors.affiliation: Pediatric Department, and Pediatric Department, Aarhus University Hospital, Aarhus, Denmark; and padkaer@ki.au.dk.
authors.forename: Jesper Padkær
authors.initials: JP
authors.lastname: Petersen
authors.affiliation: Pediatric Department, and.
authors.forename: Tine Brink
authors.initials: TB
authors.lastname: Henriksen
authors.affiliation: Danish Center for Neonatal Screening, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Mads Vilhelm
authors.initials: MV
authors.lastname: Hollegaard
authors.affiliation: Pediatric Department, and.
authors.forename: Pernille Kure
authors.initials: PK
authors.lastname: Vandborg
authors.affiliation: Danish Center for Neonatal Screening, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: David Michael
authors.initials: DM
authors.lastname: Hougaard
authors.affiliation: Department of Surgery, Aalborg University Hospital, Aalborg, Denmark;
authors.forename: Ole
authors.initials: O
authors.lastname: Thorlacius-Ussing
authors.affiliation: Pediatric Department, and.
authors.forename: Finn
authors.initials: F
authors.lastname: Ebbesen
mesh_terms: D016022:Case-Control Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000600:supply & distribution*; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D011159:Population Surveillance; D012720:Severity of Illness Index
chemical_list: D014453:Glucuronosyltransferase; C577641:UGT2A1 protein, human
keywords: Gilbert syndrome; UGT1A1*28; bilirubin; encephalopathy; kernicterus; neonates