Clinical and Genetic Etiologies of Neonatal Unconjugated Hyperbilirubinemia in the China Neonatal Genomes Project

Mei, Hongfang; Dong, Xinran; Wu, Bingbing; Wang, Huijun; Lu, Yulan; Hu, Liyuan; Wang, Jin; Cao, Yun; Zhang, Rong; Cheng, Guoqiang; Wang, Laishuan; Li, Zhihua; Yang, Lin; Zhou, Wenhao

doi:10.1016/j.jpeds.2021.12.038

Cited by 20 publications

(21 citation statements)

References 43 publications

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“…In order to avoid the toxic effect of free bilirubin, which lead to cell damage in the central nervous system and cause acute bilirubin encephalopathy and nuclear jaundice, a relatively reasonable diagnosis and treatment guideline for neonatal hyperbilirubinemia has been developed. In recent years, there have been many studies on the etiology and related risk factors of neonatal hyperbilirubinemia in China and abroad [10][11][12] . However, the etiology of hyperbilirubinemia is easily affected by environment and other relative factors.…”

Section: Discussionmentioning

confidence: 99%

Etiology analysis for full-term newborns with severe hyperbilirubinemia in eastern Guangdong

Lin

et al. 2022

Preprint

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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.

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Section: Discussionmentioning

confidence: 99%

Etiology analysis for full-term newborns with severe hyperbilirubinemia in eastern Guangdong

Lin

et al. 2022

Preprint

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“…Among these patients, UGT1A1 and G6PD were the top two variant genes identi ed, the contribution of UGT1A1 variants was underestimated. 4,8 Our study, as well as future investigations, will contribute to a better understanding of the genomic architecture of unconjugated hyperbilirubinemia and underscore the importance of genetic analysis in this patient population.…”

Section: Discussionmentioning

confidence: 80%

UGT1A1 variants contribution to neonatal hyperbilirubinemia: evidence from whole exome sequencing Running title: UGT1A1 variants contribution to neonatal hyperbilirubinemia

Liao,

Lin,

et al. 2024

Preprint

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Background It is widely recognized that genetic variation is among the risk factors associated with neonatal jaundice. Therefore, the objective of this study was to assess the impact of genetic variants on Chinese neonates with hyperbilirubinemia. Methods This cohort consisted of 43 cases with normal bilirubin levels, 54 cases categorized as the medium jaundice group (total serum bilirubin less than 342 umol/L), and 33 cases belonging to the high jaundice group (total serum bilirubin exceeding 342 umol/L). Whole exome sequencing was performed on the neonates to identify genetic variations. Results UGT1A1-G71R, mixed feeding and breast feeding were significantly correlated with higher bilirubin value. Homozygous SNP of CAPN12, ECT2L, SLC9B2, PLEKHA4, and hemizygous G6PD were only found in jaundice group but not in control group. Consistent with the result of linear regression, feeding pattern and UGT1A1 G71R were all correlated with level of bilirubin in Fisher exact test (p = 7.81E-13, and p = 2.48E-07, respectively). Conclusion The UGT1A1 gene variants emerged as a prominent risk factor for neonatal jaundice, significantly contributing to elevated bilirubin levels in Chinese neonates, particularly in conjunction with breastfeeding.

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“…Most neonates with inherited RBCM disorders experience jaundice at birth [2]. Thus far, the molecular research of RBCM was limited [16,17]. A previous investigation in Taiwan found that 1.2% of neonatal jaundice was caused by HS, but no molecular data were presented [18].…”

Section: Discussionmentioning

confidence: 99%

Red Blood Cell Membrane-Related Gene Variants and Clinical Risk Factors in Chinese Neonates with Hyperbilirubinemia

Lin

et al. 2023

Neonatology

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Introduction: Neonatal hyperbilirubinemia is common and remains a clinical concern in China. Since neonatal hyperbilirubinemia is linked to genetic factors, we aimed to identify the gene variants of the red blood cell membrane (RBCM) and evaluate the clinical risk factors in Chinese neonates with hyperbilirubinemia. Methods: 117 hyperbilirubinemia neonates (33 cases of moderate hyperbilirubinemia and 84 cases of severe hyperbilirubinemia) and 49 controls with normal bilirubin levels were selected as our study subjects. A customized 22-gene panel with next-generation sequencing (NGS) was designed to characterize genetic variations among the neonates. Sanger sequencing was used to verify the accuracy of the NGS. The clinical risk factors and potential effects of genetic variations in neonates with hyperbilirubinemia were subsequently assessed. Results: After data filtering, suspected pathogenic variants of UGT1A1, SLCCO1B1, and RBCM-associated gene were identified in neonates, the combined numbers of RBCM-associated gene variants were found to have differences between the hyperbilirubinemia group and the controls (p = 0.008), they were also different between severe hyperbilirubinemia and moderate hyperbilirubinemia (p = 0.008), and were correlated with an increased risk of hyperbilirubinemia (odds ratio = 9.644, p = 0.006). The UGT1A1-rs4148323 variant in neonates with hyperbilirubinemia was significantly increased as compared with the controls (p < 0.001). However, there was no statistical difference for the SLCO1B1-rs2306283 variant between the hyperbilirubinemia group and the controls. In addition, breastfeeding contributed to an increased risk of hyperbilirubinemia. Conclusion: Our study highlights that the RBCM-related gene variants are an underestimated risk factor, which may play an important role in developing hyperbilirubinemia in Chinese newborns.

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Clinical and Genetic Etiologies of Neonatal Unconjugated Hyperbilirubinemia in the China Neonatal Genomes Project

Cited by 20 publications

References 43 publications

Etiology analysis for full-term newborns with severe hyperbilirubinemia in eastern Guangdong

Etiology analysis for full-term newborns with severe hyperbilirubinemia in eastern Guangdong

UGT1A1 variants contribution to neonatal hyperbilirubinemia: evidence from whole exome sequencing Running title: UGT1A1 variants contribution to neonatal hyperbilirubinemia

Red Blood Cell Membrane-Related Gene Variants and Clinical Risk Factors in Chinese Neonates with Hyperbilirubinemia

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