Background Neonatal hyperbilirubinemia causing jaundice is common in East Asian population. Uridine diphosphate glucuronosyltransferase isoenzyme (UGT1A1) glucuronidates bilirubin and converts the toxic form of bilirubin to its nontoxic form. Method A retrospective study was conducted to review clinical information of ABO hemolysis neonates (ABO HDN) admitted to the Department of Neonatology, referred for neonatal hyperbilirubinemia, in a large general hospital of southern China from 2011 to 2017. Variation status of UGT1A1 was determined by direct sequencing or genotype assays. Result Sixty-nine ABO HDNs were included into the final analysis. UGT1A1 c.211 G > A mutation (UGT1A1*6, p.Arg71Gly, rs4148323) was significantly associated with the increased bilirubin level in ABO HDNs, after adjusted by age, sex and feeding method (P = 0.019 for TBIL, P = 0.02 for IBIL). Moreover, heterozygous and/or homozygous UGT1A1 mutations in the coding sequence region were significantly associated with the increased risk of developing hazardous hyperbilirubinemia (as defined by TSB > 427 umol/L) as compared those with a normal UGT1A1 genotype (ORadj = 9.16, 95%CI 1.99–42.08, P = 0.002) in the study cohort. Conclusion UGT1A1 variant in coding region is actively involved in the pathogenesis of ABO hemolysis related neonatal hyperbilirubinemia. Genetic assessment of UGT1A1 may be useful for clinical diagnosis of neonatal unconjugated hyperbilirubinemia.

Objective To explore the etiological characteristics of severe hyperbilirubinemia in full-term newborns of eastern Guangdong. Methods Full-term newborns with severe hyperbilirubinemia in one hospital from January 2012 to December 2021 were retrospectively analyzed. The etiology was determined according to the laboratory results and clinical manifestations. Results Among 1602 full-term newborns with hyperbilirubinemia in Chaozhou area, 32.20% (580/1602) was severe hyperbilirubinemia, including 213 newborns with TSB levels reaching the recommended exchange transfusion levels and 52 cases diagnosed with prolonged jaundice. Among the causes of severe hyperbilirubinemia, neonatal hemolysis accounted for 15.17%, infection accounted for 10.17%, G6PD deficiency accounted for 9.13%, and the coexistence of multiple etiologies accounted for 6.55%, unknown etiology accounted for 50.00%. ABO hemolysis and G6PD deficiency were the most common causes in the 20 cases with bilirubin encephalopathy. 94 severe hyperbilirubinemia newborns were tested for UGT1A1*6 variant (rs4148323, c.211G > A, p.Arg71Gly,), 9 cases were 211 G to A homozygous variant, 37 cases were 211 G to A heterozygous variant, and 48 cases were wild genotypes. Conclusion The main cause for severe hyperbilirubinemia and bilirubin encephalopathy were the hemolytic disease of the newborn, G6PD deficiency and infection. UGT1A1 gene variant was also a high risk factor for neonatal hyperbilirubinemia. Targeted prevention and treatment according to the etiology may reduce the occurrence of bilirubin encephalopathy and kernicterus.

BACKGROUND Neonatal hyperbilirubinemia is one of the common diseases of newborns that typically presents with yellow staining of skin, resulting in sequelaes such as hearing loss, motor and intellectual development disorders, and even death. The pathogenic factors of neonatal hyperbilirubinemia are complex. Different cases of hyperbilirubinemia may have a single or mixed etiology. AIM To explore the etiological characteristics of severe hyperbilirubinemia in term newborns of eastern Guangdong of China. METHODS Term newborns with severe hyperbilirubinemia in one hospital from January 2012 to December 2021 were retrospectively analyzed. The etiology was determined according to the laboratory results and clinical manifestations. RESULTS Among 1602 term newborns with hyperbilirubinemia in eastern Guangdong of China, 32.20% (580/1602) was severe hyperbilirubinemia. Among the causes of severe hyperbilirubinemia, neonatal hemolysis accounted for 15.17%, breast milk jaundice accounted for 12.09%, infection accounted for 10.17%, glucose-6-phosphate dehydrogenase (G6PD) deficiency accounted for 9.14%, and the coexistence of multiple etiologies accounted for 6.55%, unknown etiology accounted for 41.72%. ABO hemolysis and G6PD deficiency were the most common causes in the 20 cases with bilirubin encephalopathy. 94 severe hyperbilirubinemia newborns were tested for uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1)*6 variant (rs4148323, c.211G>A, p.Arg71Gly), 9 cases were 211 G to A homozygous variant, 37 cases were 211 G to A heterozygous variant, and 48 cases were wild genotypes. CONCLUSION The main cause for severe hyperbilirubinemia and bilirubin encephalopathy in eastern Guangdong of China were the hemolytic disease of the newborns, G6PD deficiency and infection. UGT1A1 gene variant was also a high-risk factor for neonatal hyperbilirubinemia. Targeted prevention and treatment according to the etiology may reduce the occurrence of bilirubin encephalopathy and kernicterus.

BackgroundThis study aimed to investigate the influence of a variant of the UGT1A1 gene on the occurrence and severity of prolonged jaundice in Chinese infants at term.Methods175 infants with prolonged jaundice and 149 controls were used in this retrospective case-control study. The infants with prolonged jaundice were subdivided into the mild-medium and severe jaundice groups (TSB ≥ 342 µmol/L). The frequency and genotype distribution of the UGT1A1 and G6PD genes, and clinical parameters including sex, birth weight, delivery mode, gestational age, and feeding mode, were analyzed, and the differences in the parameters between the two groups were compared.ResultsThe allele frequency of UGT1A1*6 in the prolonged jaundice group was higher than that in the control group. Similarly, it was also higher in the severe jaundice group than in the mild-medium jaundice group. Homozygous and heterozygous UGT1A1*6 were also found more frequently in the prolonged jaundice group than in the control group. Exclusive breastfeeding, homozygous and heterozygous forms of UGT1A1*6 were significant risk indicators for prolonged jaundice. Moreover, UGT1A1*6 was the best predictor of prolonged severe jaundice.ConclusionUGT1A1*6 appears to be a risk factor for prolonged jaundice with hyperbilirubinemia in term infants of Chinese ancestry who are exclusively breastfed.