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Utility of Whole Genome Sequencing in Fetuses With Abnormal Ultrasound Findings

2026年5月20日更新者：Women's Hospital School Of Medicine Zhejiang University

Clinical Study on Prenatal Diagnosis of Fetal Abnormalities of Unknown Cause Using Whole-Genome Sequencing: A Multicenter Study

The goal of this observational study is to learn if whole-genome sequencing (WGS) can help find the genetic cause in fetuses with structural abnormalities that remain unexplained after standard genetic testing (such as karyotyping, chromosomal microarray, or whole-exome sequencing). It will also learn how WGS results may affect pregnancy management and family decision-making.

The main questions it aims to answer are:

How often does WGS identify a genetic cause in these fetuses? Does WGS find more genetic causes compared to standard genetic tests? Can combining WGS with other molecular analyses help discover new disease genes or pathways? Researchers will compare WGS results to results from standard genetic tests to see if WGS finds more genetic causes.

Participants are pregnant women whose fetuses have structural abnormalities seen on ultrasound or MRI, with negative results from routine genetic testing. Participants will:

Undergo an invasive procedure (such as amniocentesis) or provide postnatal samples as part of their regular medical care Allow the use of leftover samples for WGS and additional molecular studies Be followed until after delivery to collect information on pregnancy outcomes and neonatal health

研究概览

地位

招聘中

条件

研究类型

观察性的

注册 (估计的)

1000

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

姓名：Qiong Luo
电话号码：+86 571 89998819
邮箱：luoq@zju.edu.cn

学习地点

中国
- Zhejiang
  - Hangzhou、Zhejiang、中国、310006
    - 招聘中
    - Women's Hospital School Of Medicine Zhejiang University
    - 接触：
      
      Qiong Luo
      
      电话号码：+86 571 89998819
      
      邮箱：luoq@zju.edu.cn
  - Huzhou、Zhejiang、中国、313000
    - 招聘中
    - Huzhou Maternity & Child Care Hospital
    - 接触：
      
      Liping Qiu
      
      电话号码：+86 15906823270
      
      邮箱：392686340@qq.com
  - Quzhou、Zhejiang、中国、324000
    - 招聘中
    - Quzhou Maternal and Child Health Care Hospital
    - 接触：
      
      Yuying Zhu
      
      电话号码：+86 15257023995
      
      邮箱：zhuyuy123@163.com
  - Shaoxing、Zhejiang、中国、312000
    - 招聘中
    - Shaoxing Maternity & Child Care Hospital
    - 接触：
      
      Hualin Xu
      
      电话号码：+86 13867526767
      
      邮箱：xhl0175@sina.cn

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

成人
年长者

接受健康志愿者

不

取样方法

非概率样本

研究人群

Pregnant women aged 18 years or older with singleton pregnancies, whose fetuses have structural abnormalities detected by ultrasound or MRI between 11+0 and 32+0 weeks of gestation, and who are scheduled to undergo invasive or postnatal genetic diagnostic procedures.

描述

Inclusion Criteria:

Pregnant women aged ≥ 18 years.
Singleton pregnancy.
Gestational age between 11+0 and 32+0 weeks, with ultrasound or MRI indicating a definite structural malformation in the fetus (may be with or without soft marker abnormalities) requiring prenatal diagnosis (see Appendices 1 and 2). Fetal developmental abnormalities include those of the central nervous system, cardiovascular system, craniofacial/neck region, chest/mediastinum, abdomen/digestive tract, urinary system, skeletal system/limbs, and systemic abnormalities such as fetal hydrops, abnormally thickened placenta with hydrops, and severe growth restriction. Criteria for ultrasound soft markers and structural malformations are provided in the appendices.
Planned to undergo at least one invasive or postnatal procedure for genetic diagnosis, and consent to the use of residual diagnostic samples for research testing.
Signed unified informed consent form, agreement to follow-up, and consent for storage and submission of samples and data according to the protocol.

Exclusion Criteria:

Age < 18 years or individuals lacking full capacity for civil conduct.
Twin or multiple pregnancies.
Known parental or familial carrier status of a pathogenic variant highly consistent with the current fetal phenotype, where testing is planned only for targeted confirmation.
Refusal to consent to the storage and use of samples and data for this study.
Other conditions deemed unsuitable for participation in this study by the investigator.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

研究衡量的是什么？

主要结果指标

结果测量	措施说明	大体时间
Diagnostic yield of WGS 大体时间：8 weeks after enrollment of the last participant	Proportion of fetuses with structural malformations or significant ultrasound abnormalities in whom whole-genome sequencing (WGS) using fetal and related tissues identifies at least one pathogenic or likely pathogenic variant. Overall diagnostic yield (including pathogenic/likely pathogenic variants and variants of uncertain significance reclassified as pathogenic/likely pathogenic based on additional evidence) will also be reported.	8 weeks after enrollment of the last participant
Comparison of diagnostic increment of WGS vs. standard clinical testing pathway 大体时间：12 weeks after enrollment of the last participant	Difference in diagnostic rate (proportion of fetuses with pathogenic/likely pathogenic variants) between whole-genome sequencing (WGS) and the current standard clinical testing pathway (karyotyping, CMA/CNV-seq, WES/panel). Stratified analysis by malformation type (e.g., isolated CNS, cardiac, skeletal, multiple systems) and by pattern of system involvement will be reported.	12 weeks after enrollment of the last participant
Number of novel candidate disease genes and enriched molecular pathways 大体时间：At study completion (average 24 months after first participant enrollment)	Count of novel candidate disease genes or regulatory elements identified by integrated multi-omics analysis. List of enriched KEGG pathways and GO terms (with FDR < 0.05) associated with fetal developmental abnormalities.	At study completion (average 24 months after first participant enrollment)

次要结果测量

结果测量	措施说明	大体时间
Phenotypic stratification system and gene pathway enrichment results 大体时间：At study completion (average 24 months after first participant enrollment)	Phenotypic classification system (based on organ/system involvement: isolated, multiple, syndromic). For each subtype: (1) count and frequency of pathogenic/likely pathogenic variants; (2) count of variant types (SNV, Indel, SV, CNV); (3) list of enriched KEGG pathways and GO terms with FDR < 0.05.	At study completion (average 24 months after first participant enrollment)
Reclassification rate of variants of uncertain significance (VUS) and impact on counseling decisions 大体时间：At study completion (average 24 months after first participant enrollment)	Proportion of VUS reclassified to pathogenic/likely pathogenic or benign/likely benign after multi-omics integration. Number of participants/families with altered genetic counseling or clinical decision-making (e.g., termination, prenatal intervention, postnatal follow-up plan) due to reclassification.	At study completion (average 24 months after first participant enrollment)
Establishment of a multicenter database and biobank 大体时间：At study completion (average 24 months after first participant enrollment)	A unified, relational database containing de-identified clinical phenotypes, genotypes (WGS variants), multi-omics data (e.g., transcriptomic, epigenomic), and biospecimen inventory (e.g., DNA, RNA, plasma, tissue blocks) from participating centers. Database completion will be defined as ≥90% of expected participants with all required data types uploaded and quality-controlled. Biobank completion will be defined as ≥90% of expected biospecimens collected, processed, and stored with traceable metadata.	At study completion (average 24 months after first participant enrollment)
Standardized data submission and sharing protocols 大体时间：At study completion (average 24 months after first participant enrollment)	Completion of a written protocol document (yes/no) covering sample submission, data formats, quality thresholds, reporting template (ACMG/AMP classification), clinical data dictionary, and de-identification rules, with sign-off obtained from all participating centers' principal investigators and data managers.	At study completion (average 24 months after first participant enrollment)

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Women's Hospital School Of Medicine Zhejiang University

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2026年3月12日

初级完成 (估计的)

2027年9月12日

研究完成 (估计的)

2028年3月12日

研究注册日期

首次提交

2026年4月9日

首先提交符合 QC 标准的

2026年5月20日

首次发布 (实际的)

2026年5月26日

研究记录更新

最后更新发布 (实际的)