Genomic Sequencing in Anatomically Normal Fetuses

This cohort study will examine the clinical utility of genomic sequencing (GS) in patients undergoing prenatal diagnostic procedures (chorionic villus sampling or amniocentesis) for routine indications other than a structural fetal anomaly.

Study Overview

• Status: Recruiting
• Conditions: Pregnant Individuals Requesting Standard Microarray
• Intervention / Treatment: Device: Genomic Sequencing

Detailed Description

Individuals who request prenatal diagnostic testing with standard chromosomal microarray will be offered GS as an option to assess for additional disease risk. The GS will be limited to evaluation of single gene disorders on a curated gene list developed by our multidisciplinary team of experts. This will include only pathogenic or likely pathogenic variants in genes associated with conditions with a well-defined phenotype that may include cognitive impairment or debilitating health conditions in childhood and/or conditions that will impact maternal, fetal, neonatal, or early childhood health management with significant perinatal or pediatric morbidity or mortality. GS test results will be reported to the research participant by a clinical geneticist or genetic counselor with expertise in exome sequencing. Participants may use this information for pregnancy management including termination of pregnancy. Participants will be offered analysis for secondary findings, as recommended by the American College of Medical Genetics and Genomics. Analysis and reporting of GS will be performed by the UCSF CLIA-certified Genomic Medicine Laboratory. Blood or saliva samples will be collected on both parents to allow trio GS to determine inheritance of any potentially significant fetal variants.

The project is exploratory in nature, with a goal of contributing to a growing body of evidence regarding the clinical utility of GS in the prenatal population.

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nuriye Sahin Hodoglugil, DrPH; Phone Number: 415-353-3400; Email: Nuriye.Sahin-Hodoglugil@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco
      • Contact: Nuriye Sahin Hodoglugil, DrPH; Email: Nuriye.Sahin-Hodoglugil@ucsf.edu
      • Principal Investigator: Mary Norton, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Pregnant patients who are:

• Pregnant with a structurally normal fetus (singleton or multiple gestation)
• Planning to undergo prenatal diagnosis by either chorionic villus sampling or amniocentesis with chromosome microarray analysis for routine indications
• Planning, or have already completed expanded carrier screening

Exclusion Criteria:

Pregnant patients who:

• Decline prenatal diagnostic testing
• Are pregnant and their fetus has a known anomaly
• Declined chromosomal microarray analysis of expanded carrier screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Genomic Sequencing	Device: Genomic Sequencing; Individuals who request prenatal diagnostic testing with standard chromosomal microarray will be offered genomic sequencing (GS) as an option to assess for additional disease risk.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of pathogenic or likely pathogenic variants with genomic sequencing	Proportion of positive genetic diagnosis among all pregnancies with anatomically normal fetuses	Up to 2 months after enrollment

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Mary Norton, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: January 8, 2024
• First Submitted That Met QC Criteria: January 8, 2024
• First Posted (Actual): January 18, 2024

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 23-38946

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No