Study on Early Genetic Screening and Precise Strategy of Neonatal Critical Illness

Study Overview
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Brief Summary
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The researchers hope to establish an overall program of early genetic screening for neonatal critical illness in China, and to develop precise intervention strategies to assist clinical diagnosis and treatment of hereditary critical illness.

Detailed Description
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Reducing the rate of neonatal death and disability is an important part of health education in China, and genetic diseases are an important cause of neonatal death. At present, with the development of life support platform technology, the treatment level of critically ill newborns has been rapidly improved. How to quickly diagnose and early precise intervention is the key to further break through the diagnosis and treatment of genetic diseases. Based on the neonatal genome project carried out in the early stage, the research group based on the genetic diagnosis results of over 10000 cases of neonatal critical illness cohort, studied the genetic disease spectrum of neonatal critical illness in line with the actual situation in China. In terms of detection technology, based on the second-generation sequencing technology, we established a critical illness screening gene sequencing combination including 300 genes; In the aspect of data analysis, an intelligent analysis process integrating clinical phenotype and gene sequencing data was established; In terms of clinical diagnosis and treatment, we cooperated with 5 maternity and children's hospitals in Shanghai to carry out multi center clinical verification, and formed the implementation plan of early universal genetic screening for neonatal critical illness. Through this project, we will carry out genetic disease screening research on neonatal critical diseases, focus on typical clinical manifestations such as encephalopathy, immunodeficiency, metabolic diseases, and carry out molecular autopsy on neonatal death cases to identify potential genetic causes, so as to provide basis for the research of corresponding early precise intervention strategies, and achieve the purpose of reducing neonatal death and disability rate.

Official Title
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Study on Early Genetic Screening and Precise Strategy of Neonatal Critical Illness

Conditions
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Genetic Screening, Hereditary Disease, Newborn, Stillbirth

Intervention / Treatment
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* Other: No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postnatal age less than 100 days; Perinatal death after 20 weeks of gestation (more than 500 g) Can be retained biological samples for genetic screening; Biological parent or guardian's informed consent. Exclusion Criteria: Reluctance of parents to use genetic sequencing data for subsequent research; Parents under 18 years of age or incapacitated for decision-making; subjects older than 100 days; Perinatal death less than 20 weeks of gestation or weight less than 500 g; Inherited metabolic diseases with chromosomal abnormalities; Multiple pregnancies; Lack of access to biological samples from which DNA can be extracted; Failure to sign informed consent.

Ages Eligible for Study
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Maximum Age: 100 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sick Neonates or Stillbirth<br>Infants and their parents enrolled through Neonatal Intensive Care Unit or stillbirths through Obstetrics Department of member hospitals who are un-randomized to receive genomic sequencing. Results disclosure sessions will include a discussion of: family history report, results from standard newborn screening, any potentially medically relevant findings from the baby's medical history/ physical exam, and the results of the genomic sequencing report. | Other: No intervention<br>* It's only observational study. No interventions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gene Mutation | To detect the mutation and characterize the genetic architecture and risk variants (911 variants of 146 genes, for example, AGT, AGTR1, CA12, CD2AP et al) of subjects using different genomic methods | In 3 months after receipt of the samples |