guideSEQ: Genomic Understanding, Impact, Decision & Ethics in Prenatal Sequencing (guideSEQ)

This study looks at whether genome sequencing should be used more routinely during pregnancy, even when ultrasounds look normal. Genome sequencing can examine nearly all of a baby's genes and may find genetic conditions that standard tests do not detect. Researchers will compare this test with current prenatal testing to see if it provides helpful information for families and doctors. The study will also explore how parents decide what kinds of genetic information they want to receive and how this information affects their experience during pregnancy. The goal is to understand whether genome sequencing can be used in a way that is helpful, responsible, and supportive for families in the future.

Study Overview

• Status: Recruiting
• Conditions: Prenatal Genetic Diagnosis
• Intervention / Treatment: Genetic: Genome Sequencing (GS)

Detailed Description

This multicenter, observational cohort study will evaluate prenatal sequencing among pregnancies with no fetal structural anomalies recruited at university based medical centers and evaluated at the New York Genome Center. Pregnancies with no fetal structural anomalies and meeting eligibility criteria will be enrolled into the study.

The prenatal sequencing group will be used to determine the frequency of pathogenic, likely pathogenic, and uncertain genomic variants identifiable by sequencing and the relative yield of sequencing. The prenatal sequencing group will be evaluated to understand the psychosocial needs of pregnant couples. Mothers, fathers and infants will be followed through 1 year postpartum.

The main objective of this multi-center collaborative study is to evaluate genome sequencing as a prenatal diagnostic tool in pregnancies with no known structural anomalies. Specifically, the aims are as follows:

Aim 1: Determine in pregnancies with a normal finding on ultrasound imaging, the frequency and types of fetal and maternal genetic conditions identified by GS, which impact clinical care. The goal is to understand the scope of these conditions, explore appropriate reporting criteria in pregnancy, and the role of genetic conditions in maternal morbidity and mortality.

Aim 2: Determine parental attitudes, choices, and the impact of offering prenatal whole genome sequencing as a genetic diagnostic screen in pregnancies with normal ultrasound anatomy. Clinician and community perspectives on the utility of prenatal GS as a non-invasive tool will be evaluated.

Aim 3: Expand the infrastructure for the standardized collection of prenatal genotype and phenotype data that is required to maximize future interpretive algorithms.

• Study Type: Interventional
• Enrollment (Estimated): 1042
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Camila Zarate, MPH; Phone Number: 646-300-0197; Email: cz2888@cumc.columbia.edu
• Study Contact Backup: Name: Jessica Giordano, MS, CGC; Phone Number: 516-521-5604; Email: jlg2197@cumc.columbia.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Active, not recruiting
      • Boston Childrens Hospital
  • New York
    • New York, New York, United States, 10013
      • Active, not recruiting
      • New York Genome Center
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center (CUIMC)
      • Principal Investigator: Ronald Wapner, MD
      • Contact: Camila Zarate, MPH; Phone Number: 646-300-0197; Email: cz2888@cumc.columbia.edu
      • Contact: Jessica Giordano, MS, CGC; Phone Number: 516-521-5604; Email: jlg2197@cumc.columbia.edu

Participation Criteria

Eligibility Criteria

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

Study Population

Pregnant individuals undergoing prenatal diagnostic testing (CVS or amniocentesis) whose pregnancies had no major fetal structural anomalies.

Description

Inclusion Criteria:

• Patient planned chorionic villus sampling (CVS) or amniocentesis in the absence of major fetal structural anomalies (minor anomalies are eligible, the HPO (Human Phenotype Ontology) will not be used by the analyst)
• Certified genetic counselor involved in care

Exclusion Criteria:

• A major structural anomaly
• Maternal or paternal age less than 18 years old
• Parental unwillingness to participate in 1 year of postnatal follow-up
• Language barrier (non-English or Spanish speaking)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incremental Genomic Frequency	The incremental frequency of fetal genetic conditions identified and reported by genomic sequencing (GS) compared to those found by standard-of-care (SOC) testing, including pathogenic, likely pathogenic, or variant of uncertain significance (VUS) variants identified by sequencing and deemed reportable by the Variant Adjudication Committee	Baseline to 12 months postpartum.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and type of pathogenic and likely pathogenic (P/LP) genomic findings by SOC and GS independently		Baseline to 12 months postpartum.
Percent and type of P/LP findings reported		Baseline to 12 months postpartum.
Percent of fetal P/LP findings requiring adjudication		Baseline to 12 months postpartum.
Turnaround time of SOC and GS testing		Baseline to 12 months postpartum.
Frequency of reportable genomic findings in mother		Baseline to 12 months postpartum.
Frequency of participants electing to undergo standard vs tiered reporting		Baseline to 12 months Postpartum
Comparison of the demographic characteristics between these two groups		Baseline to 12 month Postpartum
Frequency of participants opting in to reporting of strong variants of uncertain Significance		Baseline to 12 month postpartum
Frequency and type of strong VUS results amongst people who opt in to receiving them		Baseline to 12 month postpartum
Frequency of VUS findings by SOC vs GS testing, amongst people who opt in to receiving them on GS		Baseline to 12 months postpartum
Comparison of the demographic characteristics between those who opt in and those who opt out of receiving strong VUS results		Baseline to 12 month postpartum
Frequency of participants opting out of reporting on copy number variants associated with susceptibility to neurodevelopmental disorders		Baseline to 12 months postpartum
Comparison of demographic characteristics between those who opt in and those who opt out of receiving susceptibility CNV results		Baseline to 12 month postpartum
Frequency of participants opting in to receive results for conditions up to and including age 18		Baseline to 12 months postpartum
Frequency of reportable findings that may cause symptom presentation at any point during childhood (up to and including age 18) amongst those who opt in		Baseline to 12 months postpartum
Comparison of the demographic characteristics between those who opt in to receive results with possible symptom presentation up to and including age 18 vs those who elect only reporting of variants with symptom presentation up to and including only age 7		Baseline to 12 months postpartum
Frequency of participants electing to receive secondary findings per ACMG (American College of Medical Genetics) criteria		Baseline to 12 months postpartum
Frequency of ACMG secondary findings amongst those who opt in		Baseline to 12 months postpartum
Frequency of ACMG secondary findings that would have been reported regardless of this option given immediate implications for maternal health in the peripartum period		Baseline to 12 months postpartum
Comparison of the demographic characteristics between those electing to receive ACMG secondary findings vs those declining		Baseline to 12 months postpartum
Frequency of false positive and negative GS results as assessed by one year of age		Baseline to 12 months postpartum
Number of specialists added to the care of the pregnancy, delivery, and newborn care (as applicable) based on the reported genetic results		Baseline to 12 months postpartum.
Pairwise correlations of each of the four-tiered consenting decisions	Pairwise correlations will be evaluated using responses collected through the structured consent administered at enrollment Outcome measures will include the proportion (%) of participants selecting each consent option and correlation coefficients describing relationships between consent decisions across tiers.	Baseline to 12 months postpartum

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Ronald Wapner, MD, Columbia University Irving Medical Center (CUIMC)

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2026
• Primary Completion (Estimated): July 31, 2029
• Study Completion (Estimated): July 31, 2029

Study Registration Dates

• First Submitted: May 20, 2026
• First Submitted That Met QC Criteria: May 20, 2026
• First Posted (Actual): May 28, 2026

Study Record Updates

• Last Update Posted (Actual): July 15, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Genome Sequencing
• Other Study ID Numbers: ACYY0180; 2R01HD055651-16 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with the NIH Genomic Data Sharing policy, sequencing data and clinical data will be shared with other scientific investigators.
• IPD Sharing Time Frame: At the conclusion of the study, the final dataset will be prepared by Columbia and Broad for archiving and sharing.
• IPD Sharing Access Criteria: Raw genomic data (CRAM/VF) and detailed phenotype information will be submitted to the RIFGC. Controlled access to this repository is governed by dbGaP authorization requests and supervised by the consortium. Raw data, when possible, are available through AnVIL. We will also utilize governance and standards including Clinical Laboratory Improvement Amendments, Health Insurance Portability and Accountability Act (HIPAA), Fast Healthcare Interoperability Resources (FHIR) Health Level 7 (HL7), United States Core Data for Interoperability (USCDI), and the National Center for Biotechnology Information (NCBI) MedGen.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No