The Effect and Mechanism of Gene Variation on Neonatal Hyperbilirubinemia

NCT ID: NCT06186349

Last Updated: 2024-01-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

2000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-09-01

Study Completion Date

2024-12-31

Brief Summary

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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.

Detailed Description

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Adverse reactions: In this study, only 3 drops of neonatal heel peripheral blood were collected for genetic analysis and statistical analysis of percutaneous jaundice values. No human trials were involved. Family members were willing to know the genetic test results and the genetic test results were positive. Family members may have a certain psychological burden. We will provide free professional genetic counseling, as detailed as possible to inform the hazards of this genetic defect, treatment and other related information to help. Psychiatrists can be arranged for free psychological counseling if necessary.

Ethical approval: This clinical study follows the Helsinki Declaration ( 2013 edition ), the ethical principles of human medical research and the relevant clinical research norms and regulations in China.

This clinical study was approved by the Research Ethics Committee / Institutional Review Boards ( REC/IRBs ).

This clinical study is an observational clinical study initiated by researchers. The clinical research protocol ( including informed consent and case report forms, etc. ) and other information provided to the family members or guardians of the newborn were reviewed and approved by the ethics committee of the clinical research team leader unit and the participating units.

Informed consent: Before the start of the clinical study, the researchers completely and comprehensively introduced the purpose, process, method, and the interests and risks of the newborn to the parents or legal representatives who met the inclusion criteria. A written informed consent form was given to each parent or guardian of the newborn before enrollment, so that he / she had sufficient time to consider whether to consent to the collection of neonatal information to participate in this clinical study. After obtaining the informed consent of each newborn 's parent or legal representative and signing the informed consent form, researchers can begin to collect relevant data.

Privacy protection: All members of the research team, including the primary researchers and their authorized researchers, must comply with all local and regional regulatory requirements and applicable privacy regulations.

Each newborn participating in this study will be assigned a unique number and an institutional identifier.

All research data will be stored in a confidential electronic system and stored for at least 3 years after the completion of the study.

The coding table for recording neonatal information and research will be kept by the researcher (PI) in a locked file cabinet or in a password-protected database. Only researchers and their authorized researchers have the right to access the coding table.

The coding table that records the name of the hospital and the institution identification number will be saved by the research team in a locked file cabinet, which is only limited to access by limited research members. The identity of each subject of observation should be kept confidential in research reports and related publications.

Conditions

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Neonatal Hyperbilirubinemia

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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non-significant hyperbilirubinemia

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

Genomic sequencing

Intervention Type 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.

significant hyperbilirubinemia

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

Genomic sequencing

Intervention Type 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.

severe hyperbilirubinemia

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

Genomic sequencing

Intervention Type 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

500 cases ( TSB / TCB ≥ 428umol / L )

Genomic sequencing

Intervention Type 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.

Interventions

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Genomic sequencing

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.

Intervention Type GENETIC

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* 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
Minimum Eligible Age

1 Day

Maximum Eligible Age

28 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sixth Affiliated Hospital, Sun Yat-sen University

OTHER

Sponsor Role lead

Responsible Party

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HaoHu

Project leader

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Hu Hao

Role: STUDY_DIRECTOR

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

Locations

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The Sixth Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Hu Hao

Role: CONTACT

86-020-38777850

Wenna Lin

Role: CONTACT

86-020-38777850

Facility Contacts

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Hu Hao

Role: primary

86-020-38777850

References

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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.

Reference Type RESULT
PMID: 30704229 (View on PubMed)

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.

Reference Type RESULT
PMID: 30119720 (View on PubMed)

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.

Reference Type RESULT
PMID: 20022574 (View on PubMed)

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.

Reference Type RESULT
PMID: 26727668 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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EMGVNHB

Identifier Type: -

Identifier Source: org_study_id

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