Recruiting

NCT Number: NCT07610590

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

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Prenatal Genetic Diagnosis

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Boston Childrens Hospital, Boston, Massachusetts, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Genome Sequencing (GS)

Genetic

Genome sequencing (GS) is a genetic test that involves reading the genome to identify genetic changes (also known as "genetic variants") that can cause differences in human development and disease.

Primary outcomes

Incremental Genomic Frequency

Time frame: Baseline to 12 months postpartum.

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

Secondary outcomes

Frequency and type of pathogenic and likely pathogenic (P/LP) genomic findings by SOC and GS independently

Time frame: Baseline to 12 months postpartum.
Percent and type of P/LP findings reported

Time frame: Baseline to 12 months postpartum.
Percent of fetal P/LP findings requiring adjudication

Time frame: Baseline to 12 months postpartum.
Turnaround time of SOC and GS testing

Time frame: Baseline to 12 months postpartum.
Frequency of reportable genomic findings in mother

Time frame: 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

Time frame: Baseline to 12 months postpartum.
Frequency of participants electing to undergo standard vs tiered reporting

Time frame: Baseline to 12 months Postpartum
Comparison of the demographic characteristics between these two groups

Time frame: Baseline to 12 month Postpartum
Frequency of participants opting in to reporting of strong variants of uncertain Significance

Time frame: Baseline to 12 month postpartum
Frequency and type of strong VUS results amongst people who opt in to receiving them

Time frame: Baseline to 12 month postpartum
Frequency of VUS findings by SOC vs GS testing, amongst people who opt in to receiving them on GS

Time frame: 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

Time frame: Baseline to 12 month postpartum
Frequency of participants opting out of reporting on copy number variants associated with susceptibility to neurodevelopmental disorders

Time frame: Baseline to 12 months postpartum
Comparison of demographic characteristics between those who opt in and those who opt out of receiving susceptibility CNV results

Time frame: Baseline to 12 month postpartum
Frequency of participants opting in to receive results for conditions up to and including age 18

Time frame: 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

Time frame: 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

Time frame: Baseline to 12 months postpartum
Frequency of participants electing to receive secondary findings per ACMG (American College of Medical Genetics) criteria

Time frame: Baseline to 12 months postpartum
Frequency of ACMG secondary findings amongst those who opt in

Time frame: 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

Time frame: Baseline to 12 months postpartum
Comparison of the demographic characteristics between those electing to receive ACMG secondary findings vs those declining

Time frame: Baseline to 12 months postpartum
Pairwise correlations of each of the four-tiered consenting decisions

Time frame: Baseline to 12 months postpartum

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.
Frequency of false positive and negative GS results as assessed by one year of age

Time frame: Baseline to 12 months postpartum

Study contacts

Contact information is provided by the study sponsor or research team.

Camila Zarate, MPH

CONTACT

[email protected]

646-300-0197

Jessica Giordano, MS, CGC

CONTACT

[email protected]

516-521-5604

Sponsors and collaborators

Lead sponsor

Columbia University

Other

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Registry information

Acronym: guideSEQ

Important dates

Study start: 2026
Primary completion: 2029
Study completion: 2029
First posted: May 28, 2026
Registry last updated: Jul 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Recruiting

GRACE - Genetic Insights Into Early pRegnancy Loss Using Cell-free fEtal DNA

NCT07639333

Abortion, Spontaneous, Female Urogenital Diseases and Pregnancy Complications

Rennes, France

View Trial Details

Key information

Conditions

Age range

Sex eligibility

Study type

Phase

Primary location

About this study

Who can participate

Treatment and study plan

Genome Sequencing (GS)

Primary outcomes

Incremental Genomic Frequency

Secondary outcomes

Frequency and type of pathogenic and likely pathogenic (P/LP) genomic findings by SOC and GS independently

Percent and type of P/LP findings reported

Percent of fetal P/LP findings requiring adjudication

Turnaround time of SOC and GS testing

Frequency of reportable genomic findings in mother

Number of specialists added to the care of the pregnancy, delivery, and newborn care (as applicable) based on the reported genetic results

Frequency of participants electing to undergo standard vs tiered reporting

Comparison of the demographic characteristics between these two groups

Frequency of participants opting in to reporting of strong variants of uncertain Significance

Frequency and type of strong VUS results amongst people who opt in to receiving them

Frequency of VUS findings by SOC vs GS testing, amongst people who opt in to receiving them on GS

Comparison of the demographic characteristics between those who opt in and those who opt out of receiving strong VUS results

Frequency of participants opting out of reporting on copy number variants associated with susceptibility to neurodevelopmental disorders

Comparison of demographic characteristics between those who opt in and those who opt out of receiving susceptibility CNV results

Frequency of participants opting in to receive results for conditions up to and including age 18

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

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

Frequency of participants electing to receive secondary findings per ACMG (American College of Medical Genetics) criteria

Frequency of ACMG secondary findings amongst those who opt in

Frequency of ACMG secondary findings that would have been reported regardless of this option given immediate implications for maternal health in the peripartum period

Comparison of the demographic characteristics between those electing to receive ACMG secondary findings vs those declining

Pairwise correlations of each of the four-tiered consenting decisions

Frequency of false positive and negative GS results as assessed by one year of age

Study contacts

Sponsors and collaborators

Lead sponsor

Collaborators

Registry information

Important dates

Related clinical trials

GRACE - Genetic Insights Into Early pRegnancy Loss Using Cell-free fEtal DNA