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Utility of Whole Genome Sequencing in Fetuses With Abnormal Ultrasound Findings

20. maj 2026 opdateret af: 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

Studieoversigt

Status

Rekruttering

Betingelser

Undersøgelsestype

Observationel

Tilmelding (Anslået)

1000

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Studiesteder

  • Kina
    • Zhejiang
      • Hangzhou, Zhejiang, Kina, 310006
        • Rekruttering
        • Women's Hospital School of Medicine Zhejiang University
        • Kontakt:
      • Huzhou, Zhejiang, Kina, 313000
        • Rekruttering
        • Huzhou Maternity & Child Care Hospital
        • Kontakt:
      • Quzhou, Zhejiang, Kina, 324000
        • Rekruttering
        • Quzhou Maternal and Child Health Care Hospital
        • Kontakt:
      • Shaoxing, Zhejiang, Kina, 312000
        • Rekruttering
        • Shaoxing Maternity & Child Care Hospital
        • Kontakt:

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Prøveudtagningsmetode

Ikke-sandsynlighedsprøve

Studiebefolkning

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.

Beskrivelse

Inclusion Criteria:

  1. Pregnant women aged ≥ 18 years.
  2. Singleton pregnancy.
  3. 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.
  4. 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.
  5. 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:

  1. Age < 18 years or individuals lacking full capacity for civil conduct.
  2. Twin or multiple pregnancies.
  3. 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.
  4. Refusal to consent to the storage and use of samples and data for this study.
  5. Other conditions deemed unsuitable for participation in this study by the investigator.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Diagnostic yield of WGS
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Phenotypic stratification system and gene pathway enrichment results
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Women's Hospital School Of Medicine Zhejiang University

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

12. marts 2026

Primær færdiggørelse (Anslået)

12. september 2027

Studieafslutning (Anslået)

12. marts 2028

Datoer for studieregistrering

Først indsendt

9. april 2026

Først indsendt, der opfyldte QC-kriterier

20. maj 2026

Først opslået (Faktiske)

26. maj 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

26. maj 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

20. maj 2026

Sidst verificeret

1. marts 2026

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • IRB-20260095-R

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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