Prenatal Genetic Diagnosis by Genomic Sequencing

NCT03936101 | Completed Results

• 2 other identifiers: AAAS2118R01HD055651
• Study Type: observational
• Target: 1,097
• Locations: 1 country
• Sites: 5

Brief Summary

This study is evaluating the impact of prenatal sequencing on the management of fetuses with ultrasound abnormalities. The hypothesis is that a significant subset of fetal abnormalities have a genetic cause that can be identified by sequencing and that prenatal knowledge of this information will improve prenatal care, reduce unnecessary diagnostic testing, reduce the cost of care, and improve the quality of life for both the child and the family.

Conditions

Fetal Structural Anomalies

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Had Reportable Variants

  Reportable variants: defined as either Pathogenic / Likely pathogenic (P/LP) or variant of uncertain significance (VUS) identified by sequencing and deemed reportable by the Variant Adjudication Committee.

  At end of study, approx 4 years

• Healthcare Costs

  Healthcare costs from time of diagnosis of anomaly to infant discharge between sequenced and unsequenced groups.

  From time of diagnosis of anomaly to infant discharge

Secondary Outcomes (21)

• Gestational Age at Delivery

  At time of delivery

• Neonatal Outcomes

  Up to 28 days after birth

• Number of Deaths

  From discharge to 12 months postpartum

• NICU Stay Duration

  From discharge to 12 months postpartum

• Length in Centimeters

  12 months postpartum

Study Arms (2)

Prenatally Sequenced Group

750 trios with fetal structural anomalies who receive prenatal sequencing from the study

Diagnostic Test: Prenatal Genomic Sequencing

No Prenatal Sequencing (Unsequenced) Group

350 trios with fetal structural anomalies who do not have prenatal sequencing

Interventions

Prenatal Genomic Sequencing DIAGNOSTIC_TEST

Whole genome sequencing (which initially will be masked and reported as exome only)

Prenatally Sequenced Group

Eligibility Criteria

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

Study Population

A total of 1,100 pregnancies with fetal structural anomalies and meeting eligibility criteria will be enrolled into the study. Of these, 750 will undergo prenatal genomic sequencing (prenatal sequencing group) and the remaining 350 pregnancies will not have any prenatal genomic sequencing (unsequenced prenatal group). Enrollment of pregnancies with an isolated nuchal translucency measurements ≥ 3.5 mm will be restricted to 5% within each group (sequenced and unsequenced) and isolated estimated fetal weight \<5th %ile also will be restricted to 5% for each group (sequenced and unsequenced).

You may qualify if:

• Prenatal sequencing group
• Fetus identified by ultrasound and/or MRI with at least one of the following:
• One or more major structural anomalies (Appendix A)
• A nuchal translucency measurement of ≥ 3.5 mm
• A fetus less than 24 weeks 0 days gestation with normal anatomy and sonographically estimated fetal weight \<5th %ile without maternal hypertension, type I diabetes, or other maternal disorders known to alter fetal growth.
• Negative prenatal CMA (or those with CMA findings not related to the ultrasound finding)
• Singleton or twin gestation
• Gestational age less than 36 weeks, 0 days to allow for availability of sequencing results before delivery
• Unsequenced Group
• Fetus identified by ultrasound and/or MRI with at least one of the following:
• One or more major structural anomalies (Appendix A)
• A nuchal translucency measurement of ≥ 3.5 mm
• A fetus less than 24 weeks 0 days gestation with normal anatomy and sonographically estimated fetal weight \<5th %ile without maternal hypertension, type I diabetes, or other maternal disorders known to alter fetal growth
• Negative prenatal or postnatal CMA (or those with CMA findings not related to the ultrasound finding)
• Declined prenatal sequencing

You may not qualify if:

• Prenatal Sequencing Group
• Prenatal sequencing or planned prenatal sequencing performed outside of the study, including gene panels
• Maternal or paternal age less than 18 years old
• Proven infectious or teratogenic cause of fetal anomaly
• Planned termination of the pregnancy
• Unavailable blood or saliva samples from both biologic parents prior to sequencing
• Parental unwillingness to participate in 1 year postnatal follow-up
• Language barrier (non-English or Spanish speaking)
• Previous consent to the unsequenced prenatal group or enrollment in a previous pregnancy
• Unsequenced Group
• Maternal or paternal age less than 18 years old
• Proven infectious or teratogenic cause of fetal anomaly
• Planned termination of the pregnancy
• Parental unwillingness to participate in 1 year postnatal follow-up
• Language barrier (non-English or Spanish speaking)

Sponsors & Collaborators

• Columbia University: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Baylor College of Medicine: collaborator
• University of North Carolina: collaborator
• The George Washington University Biostatistics Center: collaborator
• Oregon Health and Science University: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator
• The University of Texas Health Science Center, Houston: collaborator
• Broad Institute of MIT and Harvard: collaborator
• The Jackson Laboratory: collaborator

Study Sites (5)

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of North Carolina Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Children's Hospital, Cincinnati Medical Center

Cincinnati, Ohio, 45229, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

UT Health Houston

Houston, Texas, 77030, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Remaining DNA from trios will be stored in a biorepository. Plasma from Streck tubes will be retained as well.

Results Point of Contact

• Title: Jessica L Giordano, CGC
• Organization: Columbia University

jlg2197@cumc.columbia.edu

516-521-5604

Study Officials

• Ronald Wapner, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Reproductive Genetics, Department of OBGYN

Study Record Dates

• First Submitted: March 25, 2019
• First Posted: May 3, 2019
• Study Start: June 28, 2019
• Primary Completion: March 25, 2024
• Study Completion: March 25, 2024
• Last Updated: October 27, 2025
• Results First Posted: October 27, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After study completion.
• Access Criteria: Through dbGaP or other controlled access databases.

Locations

US (5)