Accurate Assessment and Intervention Research on Newborn Whole Genome Sequencing and Genetic Disease Risk

NCT07365254 | Recruiting

• 1 other identifier: IRB-20250021-R
• Study Type: observational
• Target: 1,000,000
• Locations: 1 country
• Sites: 1

Brief Summary

Maternal and infant health is the foundation of public health, and its status directly reflects the overall health level of the population. With rapid socioeconomic development and increasingly severe environmental issues, health problems among women and children have become more widespread and diverse. In the new era, maternal and child health faces new challenges, with higher demands in areas such as reproductive health promotion, birth defect prevention, maternal and infant safety, and childhood disease prevention. Cohort studies, as an epidemiological research method for exploring disease etiology, involve recruiting participants before or during pregnancy and conducting follow-ups on pregnancy, childbirth, and maternal and child health outcomes after birth to identify various factors influencing diseases and health. Focusing on the early stages of life, this approach is an effective method for studying the associations between environmental, genetic, and behavioral risk factors during early life and embryonic development, fetal health, and infant health. This project plans to conduct long-term follow-ups on couples and their offspring on a family basis, while collecting biological samples at multiple time points. A systematic multi-dimensional assessment, based on clinical information and multi-omics data from the enrolled population, will be used to infer the causes of reproductive and pregnancy-related diseases and developmental abnormalities, identify new biomarkers for pregnancy-related diseases, establish predictive models, and recognize risk factors in the early life of offspring, thereby providing guidance for the prevention and control of reproductive and developmental diseases.

Conditions

Genetic Disease

Keywords

Newborn; Multiomics

Outcome Measures

Primary Outcomes (6)

• Whole-genome sequencing data

  Complete 30-40X whole-genome sequencing of the serum cfDNA sample according to the instructions of the DNBSEQ-T7RS High-throughput Sequencing Kit (FCL PE100) V2.0, and perform bioinformatics analysis of the sequencing data.

  After the completion of sample collection, an average of 1 year.

• Concentration of metabolite

  The concentration of each metabolite was analyzed and calculated using the automated targeted metabolic absolute quantification software HMQuant, independently developed by BGI.

  After the completion of sample collection, an average of 1 year.

• Construction and sequencing of cfRNA from maternal peripheral blood

  The library construction and quality control were performed according to the BGI PALM-seq library construction method, followed by cfRNA sequencing. The PALM-seq sequencing bioinformati

  After the completion of sample collection, an average of 1 year.

• Whole-genome DNA methylation data

  Combining bisulfite treatment with high-throughput sequencing technology enables the efficient and accurate mapping of whole-genome DNA methylation profiles, making it a crucial tool for epigenomics research. Based on the domestically developed DNBSEQTM sequencing technology, BGI has independently developed a novel library preparation method utilizing double-strand cyclization. This approach effectively addresses the base bias issue present in traditional methylation sequencing, allowing for rapid and efficient acquisition of authentic methylation level data.

  After the completion of sample collection, an average of 1 year.

• Protein expression differences and functional analysis

  Sample protein preparation: Samples were taken from -80°C, and 50 μL of each sample was treated with urea, dithiothreitol, and iodoacetamide for reduction and alkylation. Solid-phase extraction plates were used to remove high-abundance proteins, followed by the addition of trypsin for enzymatic hydrolysis. Liquid chromatography-mass spectrometry detection: After enzymatic hydrolysis, the peptides were analyzed using nanoflow-high-performance liquid chromatography-high-resolution mass spectrometry (Lumos, Thermo) in DIA (data-independent acquisition) mode for data acquisition. Data analysis: DIA-NN software was used to identify and quantify proteins from the DIA data.

  After the completion of sample collection, an average of 1 year.

• The metagenomic data

  Vaginal secretion DNA extraction and library sequencing: Magpure Stoll DNA KF kit was used to extract DNA from vaginal secretions; Construct a metagenomic library using the MGIEasy universal DNA library preparation kit; Use Agilent 2100 Bioanalyzer to detect the fragment range and concentration of the library. Qualified libraries were sequenced using the T1 sequencing platform according to the DNBSEQ-T7RS high-throughput sequencing kit instructions. Bioinformatics analysis of metagenomic sequencing data: The metagenomic data is first subjected to quality control of the original sequences using Trimomatic software, and then contaminated sequences are removed from the processed data using fastq\_streen software, including host sequences and phix library contamination; Afterwards, the BWA aligner was used for comparison, and the human genome fragments were first removed. The microbial species composition and relative abundance were evaluated using the Metaphlan2 software.

  After the completion of sample collection, an average of 1 year.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Families with ongoing pregnancies (via assisted reproductive therap or natural conception) and newborn infants.

You may qualify if:

• Families with ongoing pregnancies (via assisted reproductive therap or natural conception) and newborn infants.

You may not qualify if:

• None

Sponsors & Collaborators

• Women's Hospital School Of Medicine Zhejiang University: lead
• Zhejiang University: collaborator
• Second Affiliated Hospital, School of Medicine, Zhejiang University: collaborator

Study Sites (1)

Women's Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310006, China

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

blood, urine, vaginal secretions, feces, amniotic cells, umbilical cord blood, pregnancy outcome (POC), placental tissue, or other tissues.

MeSH Terms

Conditions

Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Hefeng Huang

  Women's Hospital School Of Medicine Zhejiang University

  STUDY CHAIR

• Dan Zhang

  Women's Hospital School Of Medicine Zhejiang University

  STUDY CHAIR

Central Study Contacts

Hengchao Ruan, phD

CONTACT

0571-88208964; ruanhengchao@zju.edu.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2025
• First Posted: January 26, 2026
• Study Start: February 14, 2025
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: January 26, 2026

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)