122 - Prolonged hyperbilirubinemia in Japanese preterm infants is associated with the UGT1A1*6 variant

Poster Number: 122
Publication Number: 122.238

Takayuki Imaizumi, Nihon University, Itabashi-ku, Tokyo, Japan; Nobuhiko Nagano, Department Pediatrics and Child Health, Nihon Uviversity School of Medicine, Itabashi-ku, Tokyo, Japan; Daichi Katayama, Nihon University Itabashi Hospital, meguro, Tokyo, Japan; Koichiro Hara, Nihon University, Itabashi, Tokyo, Japan; Takuya Akimoto, Nihon University school of medicine, Itabashi, Tokyo, Japan; Ayako Seimiya, Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Tokyo, Japan; Ryoji Aoki, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan; Midori Hijikata, Nihon University Itabashi Hospital, itabashi, Tokyo, Japan; Aya Okahashi, Nihon university school of medcine, Itabashi, Tokyo, Japan; Ichiro Morioka, Nihon University School of Medicine, Itabashi, Tokyo, Japan

Background: Proper management of prolonged hyperbilirubinemia is important to prevent the development of bilirubin encephalopathy in preterm infants in Japan. Breastfeeding is a known cause of prolonged hyperbilirubinemia due to UDP glucuronosyltransferase family 1A1 (UGT1A1) genetic polymorphisms in Asian neonates.

Objective: To identify clinical predictors for prolonged hyperbilirubinemia in Japanese preterm infants < 30 wks’ gestational age (GA).

Design/Methods: A hospital-based prospective cohort study was conducted at Nihon University Itabashi Hospital with approval by the Ethics Committees (no. RK211109-4). Infants born at < 30 wks’ GA between 2019 and 2022 were enrolled and followed until discharge from the neonatal intensive care unit. Prolonged hyperbilirubinemia was defined as hyperbilirubinemia requiring any treatment beyond 14 days of age. Neonates were categorized into the 2 groups: those with or without prolonged hyperbilirubinemia. Clinical factors, including UGT1A1 gene hetero- or homozygous variants (UGT1A1*6 and *28), were analyzed by univariate and multivariate analyses. UGT1A1*6 and *28 variants were identified using the invader assay.

Results: Of 69 preterm infants without underlying diseases enrolled during the study period, 15 infants developed prolonged hyperbilirubinemia (22%). Of 15 infants developed prolonged hyperbilirubinemia, 9 (60%) and 2 (13%) had the UGT1A1*6 and UGT1A1*28 variants, respectively. Three clinical factors, birthweight, use of high-intensity mode phototherapy, and the presence of the UGT1A1*6 variant, were identified by univariate analysis (p< 0.05, Table 1). Multivariate analysis showed that the use of high-intensity mode phototherapy and the presence of the UGT1A1*6 variant were independently associated with prolonged hyperbilirubinemia (Table 2).

Conclusion(s): Preterm infants < 30 wks’ GA who require high-intensity mode phototherapy and have the UGT1A1*6 variant at high risk for developing prolonged hyperbilirubinemia. Therefore, we propose that UGT1A1*6 screening may be important to predict prolonged hyperbilirubinemia.