title: Association of breast-fed neonatal hyperbilirubinemia with UGT1A1 polymorphisms: 211G>A (G71R) mutation becomes a risk factor under inadequate feeding.
abstract: Breastfeeding jaundice is a well-known phenomenon, but its pathogenesis is still unclear. Increased production of bilirubin, impaired hepatic uptake and metabolism of bilirubin, and increased enterohepatic circulation of bilirubin account for most cases of pathological neonatal hyperbilirubinemia. We previously reported that 211G>A (G71R) mutation of the UGT1A1 gene is prevalent in East Asians and is associated with the development of neonatal hyperbilirubinemia. Recently, significant association of G71R mutation with hyperbilirubinemia in breast-fed neonates was reported. We enrolled 401 full-term Japanese infants, who were exclusively breast-fed without supplementation of formula before developing hyperbilirubinemia, and classified them into two groups based on the degree of maximal body weight loss during the neonatal period. We analyzed the sex, gestational age, delivery mode, body weight at birth, maximal body weight loss and genotypes of G71R and (TA)(7) polymorphic mutations of UGT1A1. Statistical analysis revealed that maximal body weight loss during the neonatal period is the only independent risk factor for the development of neonatal hyperbilirubinemia. The effect of G71R mutation on neonatal hyperbilirubinemia is significant in neonates with 5% or greater maximal body weight loss and its influence increases in parallel with the degree of maximal body weight loss. Our study indicates that G71R mutation is a risk factor for neonatal hyperbilirubinemia only in infants with inadequate breastfeeding and suggests that adequate breastfeeding may overcome the genetic predisposing factor, G71R mutation, for the development of neonatal hyperbilirubinemia.
authors.affiliation: Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Sato
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Uchida
authors.forename: Kentaro
authors.initials: K
authors.lastname: Toyota
authors.forename: Miyako
authors.initials: M
authors.lastname: Kanno
authors.forename: Taeko
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Masashi
authors.initials: M
authors.lastname: Watanabe
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Gen
authors.initials: G
authors.lastname: Tamiya
authors.forename: Kuraaki
authors.initials: K
authors.lastname: Aoki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hayasaka
mesh_terms: D001942:Breast Feeding / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D014453:Glucuronosyltransferase / Q000235:genetics*; D049669:History, 16th Century; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000453:epidemiology / Q000235:genetics*; D015994:Incidence; D007231:Infant, Newborn; D007564:Japan / Q000453:epidemiology; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme