Newborns
Conditions
Brief summary
The project will carry out the genetic testing of 10000 neonates. The aim of the project is to assess the application of targeted sequencing technology in the screening of neonatal diseases.
Detailed description
Neonatal screening (NBS) is the last step of birth defects prevention. Currently, biochemical and mass spectrometry are commonly used for NBS, but there are limited diseases and certain false positive/negative. High-throughput sequencing (NGS) has been widely used in prenatal diagnosis, tumor-targeted biomarkers detection and pathogen detection. Although the application of NGS in new screening has a broad prospect and many countries around the world have begun to explore it, there are still challenges in the selection of screening diseases, gene clinical phenotypes, genetic counseling and clinical pathway. Since 2019, our team began to explore the appllication of NGS technologies in the clinical application of tertiary prevention, combined with Clinva, HGMD, OMIM database, on the basis of screening specific disease-causing genes and mutation sites as the target, A NGS panel for Newborns in China (NeoExome) was designed, covering 542 single-gene diseases with 601 genes. The rationality and validity of the NGS panel was preliminarily verified in 3423 neonatal blood samples collected from 5 new screening centers in China. In order to further optimize the gene screening spectrum of neonatal diseases in the Chinese population, evaluate the efficacy of targeted sequencing technology in the screening and diagnosis of neonatal diseases, standardize the clinical pathway, and lay a foundation for the formulation of China's new screening NGS guidelines, the investigators further optimized the targeted sequencing package (NeoexOME-V2) on the basis of the first phase. 491 genes covering 485 single-gene genetic diseases were designed to launch the "Budding Action". The project plans to collect 10000 samples nationwide and carry out the multi-center clinical research on the application of targeted sequencing technology in the screening of neonatal diseases.
Interventions
GENETICNGS
In the Nation multicenter screening cohort, NGS testing was performed on the basis of conventional NBS to study the relationship between gene variation and disease occurrence;
Sponsors
Shanghai Children's Hospital
Xuzhou maternal and Child Health Care Hospital
Northwest Women's and Children's Hospital, Xi'an, Shaanxi
Inner Mongolia Maternal and Child Health Care Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
1 Days to 28 Days
Inclusion criteria
* \-- Subjects: all newborns (from birth to 28 days); * \-- After fully understanding the program, the guardian signs the informed consent and agrees to participate in the program.
Exclusion criteria
* Other similar clinical research projects are under way for the examined neonates; * Neonates have received transfusion of allogeneic blood products; * Newborns whose guardians explicitly refuse to participate in the program after receiving the mission. Elimination criteria * Samples that are not properly collected or stored for testing; * Samples with non-standard data records; * Samples without clinical follow-up results; * The project recalls newborns who are required to withdraw by their guardians during the follow-up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Outcome measure | From enrollment to the end of test at 3 years | Kappa coefficient to evaluate the agreement strength. Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) calculated based on the 2x2 contingency table (True Positive, False Positive, False Negative, True Negative). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The consistency of test results of NGS and conventional NBS | From enrollment to the end of testt at 8 weeks | Conventional NBS was used as the standard to study the application potential of targeted sequencing technology in neonatal screening and evaluate its consistency: ① Genetic variations in children with positive results from routine NBS screening: Genetic variation rate, genetic variations found in specific genes, population distribution characteristics, etc.; ② Application of gene sequencing technology in the diagnosis of diseases in infants and young children with positive results from routine newborn screening. 50% number of participants with consistency of test results. physiological parameter: Kappa coefficient to evaluate the agreement strength. Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) calculated based on the 2x2 contingency table (True Positive, False Positive, False Negative, True Negative). McNemar's test for discordant pairs analysis. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORLin Zou
Shanghai Children's Hospital
Outcome results
None listed