The Effect and Mechanism of Gene Variation on Neonatal Hyperbilirubinemia

NCT06186349 | Unknown DMC

• 1 other identifier: EMGVNHB
• Study Type: observational
• Target: 2,000
• Locations: 1 country
• Sites: 1

Brief Summary

Neonatal hyperbilirubinemia ( NHB ) has many causes and is difficult to diagnose, and genetic factors play an important role in the metabolism of bilirubin. However, there is no literature report on the correlation between jaundice gene polymorphism and clinical manifestation polymorphism in big data population. This project intends to conduct a prospective observational study led by the Department of Pediatrics of the Sixth Affiliated Hospital of Sun Yat-sen University and in conjunction with a multi-center cooperative hospital : ( 1 ) A total of 2,000 NHB neonatal dry blood spot samples were included for 24 genetic screening tests for 29 NHB-related genetic diseases. The construction of the gene database was completed and the carrying and pathogenicity of NHB-related genes in the population was analyzed to provide a scientific basis for the selection of mutation sites for large-scale NHB gene screening ; ( 2 ) Collect neonatal clinical data and percutaneous bilirubin levels through the hospital inpatient system and the ' percutaneous jaundice meter home monitoring + software doctor-patient interconnection ' method, complete the construction of the intelligent NHB clinical database, and analyze the impact of jaundice-related genes on NHB ; ( 3 ) Integrated analysis to understand the differences in the carrying rate of pathogenic genes in different degrees and special types of jaundice, and to explore the differences in the degree of jaundice carrying single or multiple jaundice pathogenic genes. This study will evaluate the feasibility of jaundice gene screening program in the detection of jaundice-related inherited metabolic diseases, and provide a basis for early treatment and prevention of NHB.

Conditions

Neonatal Hyperbilirubinemia

Outcome Measures

Primary Outcomes (4)

• Number of gene sequencing data in neonatal gene bank

  Each newborn that was sequenced was counted as 1. Keep all the data in the gene bank, and finally calculate the number of completed gene sequencing data.

  From birth to completion of genetic screening, the process last up to 3 months.

• Gene mutation rate

  Taking the number of newborn babies as denominator and the number of neonates with gene mutation detected in gene sequencing as molecules, the whole neonatal gene mutation rate in China was obtained.

  From birth to completion of genetic screening, the process last up to 3 months.

• carrying rate of pathogenic genes

  the carrying rate of pathogenic genes of common hereditary jaundice diseases in newborns was counted

  From birth to completion of genetic screening, the process last up to 3 months.

• phenotypic polymorphism

  analyze the correlation between gene polymorphism and clinical manifestations ( phenotypic polymorphism ) of neonatal hyperbilirubinemia.

  From birth to completion of genetic screening, the process last up to 3 months.

Study Arms (4)

non-significant hyperbilirubinemia

including 500 cases of non-significant hyperbilirubinemia ( TSB / TCB \< 205umol / L )

Genetic: Genomic sequencing

significant hyperbilirubinemia

500 cases of significant hyperbilirubinemia ( 205umol / L ≤ TSB / TCB \< 342umol / L )

Genetic: Genomic sequencing

severe hyperbilirubinemia

500 cases of severe hyperbilirubinemia ( TSB / TCB ≥ 342umol / L )

Genetic: Genomic sequencing

Extremely severe hyperbilirubinemia

500 cases ( TSB / TCB ≥ 428umol / L )

Genetic: Genomic sequencing

Interventions

Genomic sequencing GENETIC

Newborns with neonatal hyperbilirubinemia who did not randomly receive genome sequencing will receive a Genomic Newborn Sequencing Report which will include pathogenic or likely pathogenic variants identified in genes associated with childhood-onset disease.

Extremely severe hyperbilirubinemia; non-significant hyperbilirubinemia; severe hyperbilirubinemia; significant hyperbilirubinemia

Eligibility Criteria

• Age: 1 Day - 28 Days
• Sex: all
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

This study is a prospective observational study. According to the positive mutation rate of NHB-related genes in neonatal hyperbilirubinemia, P is about 30 %, the test level α = 0.05 and the allowable error δ = 2 %, n ( sample size ) = ( Uα / δ ) 2 \* p \* ( 1-P ) ≈ 2000 cases. A total of 2000 neonates were included, including 500 cases of non-significant hyperbilirubinemia ( TSB / TCB \< 205umol / L ) ; ( 2 ) 500 cases of significant hyperbilirubinemia ( 205umol / L ≤ TSB / TCB \< 342umol / L ) ; ( 3 ) 500 cases of severe hyperbilirubinemia ( TSB / TCB ≥ 342umol / L ) ; (4) Extremely severe hyperbilirubinemia 500 cases ( TSB / TCB ≥ 428umol / L ).

You may qualify if:

• Age 1-28 days
• gestational age ≥ 35 weeks
• Birth weight ≥ 2.5 kg and \< 4 kg.

You may not qualify if:

• Neonatal data with unclear clinical basic information ;
• Lack of traceability core information data ;
• data that the test results cannot be analyzed and interpreted ;
• Sample collection is not qualified and unwilling to cooperate with re-sampling.
• Newborns with severe deformity and severe lethal inherited metabolic diseases

Sponsors & Collaborators

• Sixth Affiliated Hospital, Sun Yat-sen University: lead

Study Sites (1)

The Sixth Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510655, China

RECRUITING

Related Publications (4)

• Wu J, Lu AD, Zhang LP, Zuo YX, Jia YP. [Study of clinical outcome and prognosis in pediatric core binding factor-acute myeloid leukemia]. Zhonghua Xue Ye Xue Za Zhi. 2019 Jan 14;40(1):52-57. doi: 10.3760/cma.j.issn.0253-2727.2019.01.010. Chinese.

  PMID: 30704229 RESULT

• Olusanya BO, Kaplan M, Hansen TWR. Neonatal hyperbilirubinaemia: a global perspective. Lancet Child Adolesc Health. 2018 Aug;2(8):610-620. doi: 10.1016/S2352-4642(18)30139-1. Epub 2018 Jun 28.

  PMID: 30119720 RESULT

• Watchko JF, Lin Z. Exploring the genetic architecture of neonatal hyperbilirubinemia. Semin Fetal Neonatal Med. 2010 Jun;15(3):169-75. doi: 10.1016/j.siny.2009.11.003. Epub 2009 Dec 21.

  PMID: 20022574 RESULT

• Yang H, Wang Q, Zheng L, Zheng XB, Lin M, Zhan XF, Yang LY. Clinical Significance of UGT1A1 Genetic Analysis in Chinese Neonates with Severe Hyperbilirubinemia. Pediatr Neonatol. 2016 Aug;57(4):310-7. doi: 10.1016/j.pedneo.2015.08.008. Epub 2015 Dec 2.

  PMID: 26727668 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Any newborn who joined the project, his/her parents will be informed and signed informed consent, in the newborn clinical treatment process to collect venous blood 2ml for gene sequencing and mutation screening

MeSH Terms

Conditions

Hyperbilirubinemia, Neonatal

Condition Hierarchy (Ancestors)

Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperbilirubinemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Hu Hao

  Department of Pediatrics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

  STUDY DIRECTOR

Central Study Contacts

Hu Hao

CONTACT

86-020-38777850; haohu@mail.sysu.edu.cn

Wenna Lin

CONTACT

86-020-38777850; linwn5@mail.sysu.edu.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Project leader

Study Record Dates

• First Submitted: December 13, 2023
• First Posted: January 2, 2024
• Study Start: September 1, 2023
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: January 2, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)