Prenatal Cell-free DNA Screening in Pregnancies With Diverse Genetic Risk Profiles Utilizing Targeted and Whole-exome Sequencing

NCT07106853 | Not Yet Recruiting

• 1 other identifier: IRB-20250133-R
• Study Type: observational
• Target: 1,600
• Locations: 0 countries
• Sites: N/A

Brief Summary

This multicenter study aims to recruit a minimum of 1,600 pregnant women, encompassing individuals with varying levels of genetic risk. The study particularly focuses on cases with increased fetal nuchal translucency (NT ≥3.5 mm), additional ultrasound markers, and/or fetal structural anomalies. Peripheral blood samples of eligible participants will be collected for two state-of-the-art cfDNA tests based on coordinative allele-aware target enrichment sequencing (COATE-seq): (1) a targeted panel to screen for frequent chromosomal aneuploidies, microdeletions/duplications, and dominant single-gene conditions, and (2) comprehensive whole-exome cfDNA sequencing for aneuploidies, microdeletions/duplications, monogenic variants (both dominant and recessive variants), uniparental disomy, and hydatidiform moles. The results of both cfDNA tests will be compared with those from invasive or postnatal diagnostic testing. Pregnancy outcome will be followed up to six weeks postpartum. The primary goal is to determine the clinical validity of targeted and whole exome cfDNA analyses, assessed through sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) relative to diagnostic standards. Secondary goal is to assess efficacy across diverse genetic risk populations by analyzing detection rates of pathogenic variants associated with fetal indications. The clinical utility of cfDNA screening will also be evaluated by its impact on clinical management decisions, including follow-up diagnostic procedures or prenatal/perinatal interventions.

Conditions

Genetic Disease

Outcome Measures

Primary Outcomes (1)

• Determine the clinical validity of targeted and whole exome cfDNA analyses, assessed through sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) relative to diagnostic standards.

  18 months

Secondary Outcomes (1)

• Assess efficacy across diverse genetic risk populations by analyzing detection rates of pathogenic variants associated with fetal indications.

  8 months

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

* Adult pregnant woman (≥18 years old) * Gestational age between 9+0 and 25+6 weeks * Singleton pregnancy * Pregnancy with indications for prenatal diagnosis due to: * Increased nuchal translucency (NT) ≥3.5 mm: capped at 25% of total subjects * Increased NT ≥3.5 mm AND presence of any other "soft marker" or structural anomaly: capped at 25% of total subjects * Presence of structural anomaly: at least 50% of total subjects * Agree to participate in the clinical study for being followed-up and accept at least one molecular diagnosis (diagnostic procedures performed on prenatal invasive specimens, product of conception, umbilical cord blood, or other specimens) and possible family member testing

You may qualify if:

• Adult pregnant woman (≥18 years old)
• Gestational age between 9+0 and 25+6 weeks
• Singleton pregnancy
• Pregnancy with indications for prenatal diagnosis due to:
• Increased nuchal translucency (NT) ≥3.5 mm: capped at 25% of total subjects
• Increased NT ≥3.5 mm AND presence of any other "soft marker" or structural anomaly: capped at 25% of total subjects
• Presence of structural anomaly: at least 50% of total subjects
• Agree to participate in the clinical study for being followed-up and accept at least one molecular diagnosis (diagnostic procedures performed on prenatal invasive specimens, product of conception, umbilical cord blood, or other specimens) and possible family member testing

You may not qualify if:

• Age under 18 years
• Gestational age is less than 9+0 weeks or greater than 25+6 weeks
• One parent or other family member has a known pathogenic variant linked to the fetal ultrasound finding(s)
• Conditions affecting the accuracy of cfDNA assay (e.g., maternal malignancy during pregnancy, maternal allogeneic blood transfusion, organ transplantation, or cell therapy within the past year)

Sponsors & Collaborators

• Women's Hospital School Of Medicine Zhejiang University: lead
• University of Pennsylvania: collaborator
• Chinese University of Hong Kong: collaborator

Biospecimen

Retention: SAMPLES WITH DNA

blood, chorionic villus, amniotic cells, cord blood, products of conception (POC), placenta tissues or other tissues

MeSH Terms

Conditions

Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Jinglan Zhang, PhD

CONTACT

86-18057173728; jinglanzhang@foxmail.com

Study Design

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

Study Record Dates

• First Submitted: June 11, 2025
• First Posted: August 6, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: August 6, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The IPD will be available together with the publication of the study results.