Technology Development for Noninvasive Prenatal Genetic Diagnosis Using Whole Fetal Cells From Maternal Peripheral Blood

NCT04285814 | Completed

• 2 other identifiers: AAAS91073R01HD055651
• Study Type: observational
• Target: 33
• Locations: 1 country
• Sites: 2

Brief Summary

Amniocentesis (amnio) and chorionic villus sampling (CVS) can reliably detect many smaller DNA/genetic abnormalities that cannot be reliably diagnosed by cell-free noninvasive prenatal testing (NIPT) that is in widespread use. The investigators present evidence that a cell-based form of NIPT, here called Single Fetal Cell (SFC) testing, using a blood sample from the mother can detect most or all of the genetic abnormalities that are detected using amnio or CVS. This study proposes to compare the effectiveness of SFC testing in detecting abnormalities already detected by amnio or CVS in women already undergoing these tests as part of their clinical care because of fetal ultrasound abnormalities.

Conditions

Copy Number Abnormality; Prenatal Diagnosis; Genetic Disease

Keywords

noninvasive prenatal testing; microarray; fetal cells; prenatal diagnosis

Outcome Measures

Primary Outcomes (4)

• Using a population of pregnancies with abnormal and normal karyotypes and CMAs, determine the false positive, false negative, true positive, and true negative rates of WFC testing.

  3 years

• Determine the technical success rate for WFC testing including number of scorable cells for each sample.

  3 years

• Determine the level of resolution for detecting deletions/duplications by WFC testing based on "spiked in" samples of known CNVs and on analysis of naturally occurring CNVs in fetal cells.

  3 years

• Determine capability and success rate for genotyping single gene mutations including de novo and inherited single gene mutations and benign SNPs.

  3 years

Secondary Outcomes (3)

• Evaluate WFC testing results according to gestational age at testing, specific anomalies, maternal weight, and multiple gestations.

  3 years

• Determine whether cells are more frequent in pregnancies resulting in adverse pregnancy outcomes including preeclampsia.

  3 years

• Improve methods for genotyping single cells including ability to perform genotyping and genome-wide copy number analysis on the same cell.

  3 years

Study Arms (2)

Normal CMA

150 women whose blood samples will be drawn for WFC testing who previously had a CMA performed with normal results.

Diagnostic Test: Whole Fetal Cell (WFC) Testing

Abnormal CMA

150 women whose blood samples will be drawn for WFC testing who previously had a CMA performed with abnormal results.

Diagnostic Test: Whole Fetal Cell (WFC) Testing

Interventions

Whole Fetal Cell (WFC) Testing DIAGNOSTIC_TEST

Performing WFC testing on blood specimens.

Abnormal CMA; Normal CMA

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Participants must be pregnant women.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Pregnant women presenting at the study sites who have a karyotype and/or CMA performed will be recruited for this study. Half of the women will have a normal CMA (150) and half will have an abnormal CMA (150).

You may qualify if:

• Have already had a CVS or amniocentesis (blood sample collected \>= 7 days after procedure).
• Have already received an abnormal (case) or normal (control) CMA/karyotype/FISH result from the CVS or amniocentesis.

You may not qualify if:

• Unavailability of maternal blood sample at least 7 days post-procedure.
• Language barrier (non-English or Spanish speaking and no adequate interpreter)
• Maternal age of less than 18 years
• Higher order multiple pregnancy (triplet or greater)

Sponsors & Collaborators

• Columbia University: lead
• Baylor College of Medicine: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (2)

Columbia University

New York, New York, 10032, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Remaining blood samples and products (including DNA) will be stored for future research on WFC testing.

MeSH Terms

Conditions

Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Ronald Wapner, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Chair, Research, OBGYN

Study Record Dates

• First Submitted: February 24, 2020
• First Posted: February 26, 2020
• Study Start: September 1, 2020
• Primary Completion: July 20, 2023
• Study Completion: July 20, 2023
• Last Updated: January 29, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)