The Effect and Mechanism of Gene Variation on Neonatal Hyperbilirubinemia

Neonatal Hyperbilirubinemia Clinical Trial

— EMOGVONHB  

Official title:

The Effect and Mechanism of Gene Variation on Neonatal Hyperbilirubinemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06186349
• Other study ID #: EMGVNHB
• Status: Recruiting
• Start date: September 1, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: December 2023
• Source: Sixth Affiliated Hospital, Sun Yat-sen University
• Contact: Hu Hao
• Phone: 86-020-38777850
• Email: haohu[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Gender: All
• Age group: 1 Day to 28 Days

Eligibility

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

Related Conditions & MeSH terms

• Hyperbilirubinemia
• Hyperbilirubinemia, Neonatal
• Neonatal Hyperbilirubinemia

Intervention

Genetic:
• 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.

Locations

Country	Name	City	State
China	The Sixth Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sixth Affiliated Hospital, Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.
Primary	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.