Clinical and genetic risk factors associated with neonatal severe hyperbilirubinemia: a case–control study based on the China Neonatal Genomes Project
Objective: We aimed to investigate the clinical and genetic risk factors associated with neonatal severe unconjugated hyperbilirubinemia.Methods: This was a retrospective, 1:1 matched, case–control study. We included 614 neonates diagnosed with severe unconjugated hyperbilirubinemia (serum total bil...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1292921/full |
| _version_ | 1797357644370935808 |
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| author | Xiao Wang Tiantian Xiao Jin Wang Bingbing Wu Huijun Wang Yulan Lu Yaqiong Wang Bin Chen Liyuan Hu Yun Cao Rong Zhang Guoqiang Cheng Laishuan Wang Zhihua Li Xinran Dong Lin Yang Lin Yang Wenhao Zhou Wenhao Zhou Wenhao Zhou |
| author_facet | Xiao Wang Tiantian Xiao Jin Wang Bingbing Wu Huijun Wang Yulan Lu Yaqiong Wang Bin Chen Liyuan Hu Yun Cao Rong Zhang Guoqiang Cheng Laishuan Wang Zhihua Li Xinran Dong Lin Yang Lin Yang Wenhao Zhou Wenhao Zhou Wenhao Zhou |
| author_sort | Xiao Wang |
| collection | DOAJ |
| description | Objective: We aimed to investigate the clinical and genetic risk factors associated with neonatal severe unconjugated hyperbilirubinemia.Methods: This was a retrospective, 1:1 matched, case–control study. We included 614 neonates diagnosed with severe unconjugated hyperbilirubinemia (serum total bilirubin level ≥425 μmol/L or serum total bilirubin concentration that met exchange transfusion criteria) from the China Neonatal Genomes Project in Children’s Hospital of Fudan University. Clinical exome sequencing data were analyzed using a data analysis pipeline of Children’s Hospital of Fudan University. The factors associated with severe unconjugated hyperbilirubinemia were assessed using univariable and multivariable logistic regression analyses. Interaction analyses were examined between clinical and genetic risk factors.Results: ABO/Rh incompatibility hemolysis (odds ratio [OR] 3.36, 95% confidence interval [CI] 2.32–4.86), extravascular hemorrhage (OR 2.95, 95% CI 2.24–3.89), weight loss (OR 5.46, 95% CI 2.88–10.36), exclusive breastmilk feeding (OR 3.56, 95% CI 2.71–4.68), and the homozygous mutant of UGT1A1 211G>A (OR 2.35, 95% CI 1.54–3.59) were all identified as factors significantly associated with severe unconjugated hyperbilirubinemia. The presence of UGT1A1 211G>A mildly increased the risk of severe unconjugated hyperbilirubinemia caused by ABO/Rh incompatibility hemolysis (OR 3.98, 95% CI 2.19–7.23), although the effect is not statistically significant.Conclusion: ABO/Rh incompatibility hemolysis, extravascular hemorrhage, weight loss, exclusive breastmilk feeding, and the homozygous mutant of UGT1A1 211G>A were found to be risk factors for severe unconjugated hyperbilirubinemia. Clinical factors remain the most crucial and preventable determinants in managing severe unconjugated hyperbilirubinemia, with a minimal genetic contribution. The establishment of preconception care practices and the reinforcement of screening for the aforementioned risk factors are essential steps for preventing severe unconjugated hyperbilirubinemia. |
| first_indexed | 2024-03-08T14:48:14Z |
| format | Article |
| id | doaj.art-a8b98f175f9444bf880fbabcf59dac07 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-08T14:48:14Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-a8b98f175f9444bf880fbabcf59dac072024-01-11T05:26:44ZengFrontiers Media S.A.Frontiers in Genetics1664-80212024-01-011410.3389/fgene.2023.12929211292921Clinical and genetic risk factors associated with neonatal severe hyperbilirubinemia: a case–control study based on the China Neonatal Genomes ProjectXiao Wang0Tiantian Xiao1Jin Wang2Bingbing Wu3Huijun Wang4Yulan Lu5Yaqiong Wang6Bin Chen7Liyuan Hu8Yun Cao9Rong Zhang10Guoqiang Cheng11Laishuan Wang12Zhihua Li13Xinran Dong14Lin Yang15Lin Yang16Wenhao Zhou17Wenhao Zhou18Wenhao Zhou19Center for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaChengdu Women’s and Children’s Central Hospital, The Affiliated Women’s and Children’s Hospital, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, ChinaDepartment of Neonatology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaDepartment of Neonatology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaDepartment of Neonatology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaDepartment of Neonatology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaDepartment of Neonatology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaDepartment of Neonatology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaDepartment of Neonatology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaDepartment of Neonatology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaDepartment of Neonatology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaDepartment of Pediatric Endocrinology and Inherited Metabolic Diseases, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaDepartment of Neonatology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, ChinaGuangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaObjective: We aimed to investigate the clinical and genetic risk factors associated with neonatal severe unconjugated hyperbilirubinemia.Methods: This was a retrospective, 1:1 matched, case–control study. We included 614 neonates diagnosed with severe unconjugated hyperbilirubinemia (serum total bilirubin level ≥425 μmol/L or serum total bilirubin concentration that met exchange transfusion criteria) from the China Neonatal Genomes Project in Children’s Hospital of Fudan University. Clinical exome sequencing data were analyzed using a data analysis pipeline of Children’s Hospital of Fudan University. The factors associated with severe unconjugated hyperbilirubinemia were assessed using univariable and multivariable logistic regression analyses. Interaction analyses were examined between clinical and genetic risk factors.Results: ABO/Rh incompatibility hemolysis (odds ratio [OR] 3.36, 95% confidence interval [CI] 2.32–4.86), extravascular hemorrhage (OR 2.95, 95% CI 2.24–3.89), weight loss (OR 5.46, 95% CI 2.88–10.36), exclusive breastmilk feeding (OR 3.56, 95% CI 2.71–4.68), and the homozygous mutant of UGT1A1 211G>A (OR 2.35, 95% CI 1.54–3.59) were all identified as factors significantly associated with severe unconjugated hyperbilirubinemia. The presence of UGT1A1 211G>A mildly increased the risk of severe unconjugated hyperbilirubinemia caused by ABO/Rh incompatibility hemolysis (OR 3.98, 95% CI 2.19–7.23), although the effect is not statistically significant.Conclusion: ABO/Rh incompatibility hemolysis, extravascular hemorrhage, weight loss, exclusive breastmilk feeding, and the homozygous mutant of UGT1A1 211G>A were found to be risk factors for severe unconjugated hyperbilirubinemia. Clinical factors remain the most crucial and preventable determinants in managing severe unconjugated hyperbilirubinemia, with a minimal genetic contribution. The establishment of preconception care practices and the reinforcement of screening for the aforementioned risk factors are essential steps for preventing severe unconjugated hyperbilirubinemia.https://www.frontiersin.org/articles/10.3389/fgene.2023.1292921/fullUGT1A1 polymorphismneonatal unconjugated hyperbilirubinemiarisk factorsgeneralized linear modelcase-control analysis |
| spellingShingle | Xiao Wang Tiantian Xiao Jin Wang Bingbing Wu Huijun Wang Yulan Lu Yaqiong Wang Bin Chen Liyuan Hu Yun Cao Rong Zhang Guoqiang Cheng Laishuan Wang Zhihua Li Xinran Dong Lin Yang Lin Yang Wenhao Zhou Wenhao Zhou Wenhao Zhou Clinical and genetic risk factors associated with neonatal severe hyperbilirubinemia: a case–control study based on the China Neonatal Genomes Project Frontiers in Genetics UGT1A1 polymorphism neonatal unconjugated hyperbilirubinemia risk factors generalized linear model case-control analysis |
| title | Clinical and genetic risk factors associated with neonatal severe hyperbilirubinemia: a case–control study based on the China Neonatal Genomes Project |
| title_full | Clinical and genetic risk factors associated with neonatal severe hyperbilirubinemia: a case–control study based on the China Neonatal Genomes Project |
| title_fullStr | Clinical and genetic risk factors associated with neonatal severe hyperbilirubinemia: a case–control study based on the China Neonatal Genomes Project |
| title_full_unstemmed | Clinical and genetic risk factors associated with neonatal severe hyperbilirubinemia: a case–control study based on the China Neonatal Genomes Project |
| title_short | Clinical and genetic risk factors associated with neonatal severe hyperbilirubinemia: a case–control study based on the China Neonatal Genomes Project |
| title_sort | clinical and genetic risk factors associated with neonatal severe hyperbilirubinemia a case control study based on the china neonatal genomes project |
| topic | UGT1A1 polymorphism neonatal unconjugated hyperbilirubinemia risk factors generalized linear model case-control analysis |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1292921/full |
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