Prenatal Genetic Diagnosis by Genomic Sequencing

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Total Enrollment

1097 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-06-28

Study Completion Date

2024-03-25

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Development of an Optimal Approach to Return of Results for Next-generation Sequencing for Prenatal Diagnosis

NCT02255825

Major Fetal Anomaly

WITHDRAWN NA

Perinatal Precision Medicine

NCT03211039

Genetic Diseases Genetic Syndrome Mendelian Disorders

ACTIVE_NOT_RECRUITING NA

Genomic Sequencing in Anatomically Normal Fetuses

NCT06211348

Pregnant Individuals Requesting Standard Microarray

RECRUITING NA

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

NCT04285814

Copy Number Abnormality Prenatal Diagnosis Genetic Disease

COMPLETED

Expanded Noninvasive Genomic Medical Assessment: The Enigma Study

NCT02787486

Down Syndrome Edwards Syndrome Patau Syndrome +5 more

COMPLETED

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Whole exome and whole genome sequencing (WGS) have expanded the ability to determine the genetic etiology of previously undiagnosed disorders. This study is a multicenter prospective cohort study to evaluate the emerging technology of sequencing for the management of fetuses with structural anomalies. The hypothesis is that a significant subset of fetal structural anomalies has a genetic etiology identifiable by sequencing and that prenatal knowledge of this information will improve perinatal care, reduce unnecessary diagnostic testing, reduce the cost of care, and improve quality of life for both the child and the family. The aims of this study are to investigate these multiple aspects of prenatal sequencing in a single study with an innovative integrated prospective design, which will permit a robust evaluation of the benefits and risks of delivering diagnostic and prognostic genetic testing results in a prenatal setting.

The study will determine, in a sequential population of pregnancies with selected fetal structural anomalies and a negative or non-causal chromosomal microarray (CMA), the frequency of pathogenic, likely pathogenic, and uncertain genomic variants identifiable by sequencing. To determine the impact of this information on clinical care, a control population of unsequenced pregnancies with similar structural anomalies will be prospectively recruited and the infants from both cohorts will be followed up to 1 year of age. This study component will evaluate differences in healthcare management and cost through discharge from hospital post-delivery, and perinatal and infant outcomes through 1 year of life. The educational, counseling and psychosocial impact of sequencing results during the prenatal period, in the nursery and through 1 year of life also will be evaluated. Since the analytical and clinical tools needed for the full translation of sequencing into care are still developing, optimization of bioinformatic tools to improve identification of pathogenic and likely pathogenic mutations associated with prenatal phenotypes of established disease genes will be investigated, as well as identification of new genes associated with presently undiagnosed fetal/neonatal phenotypes. This study will provide an in-depth evaluation of the prenatal diagnostic value of sequencing prior to its responsible introduction into practice and will provide independent data to guide its translation.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Fetal Structural Anomalies

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Prenatally Sequenced Group

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

Prenatal Genomic Sequencing

Intervention Type DIAGNOSTIC_TEST

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

No Prenatal Sequencing (Unsequenced) Group

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

No interventions assigned to this group

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Prenatal Genomic Sequencing

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

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

Prenatal sequencing group

1. Fetus identified by ultrasound and/or MRI with at least one of the following:

1. One or more major structural anomalies (Appendix A)
2. A nuchal translucency measurement of ≥ 3.5 mm
3. 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.
2. Negative prenatal CMA (or those with CMA findings not related to the ultrasound finding)
3. Singleton or twin gestation
4. Gestational age less than 36 weeks, 0 days to allow for availability of sequencing results before delivery

Unsequenced Group

1. Fetus identified by ultrasound and/or MRI with at least one of the following:

1. One or more major structural anomalies (Appendix A)
2. A nuchal translucency measurement of ≥ 3.5 mm
3. 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
2. Negative prenatal or postnatal CMA (or those with CMA findings not related to the ultrasound finding)
3. Declined prenatal sequencing
4. Singleton gestation

Exclusion Criteria

Prenatal Sequencing Group

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

Unsequenced Group

1. Maternal or paternal age less than 18 years old
2. Proven infectious or teratogenic cause of fetal anomaly
3. Positive prenatal NIPT screening for trisomy 21,18 or 13. Positive 22q11.2 prenatal NIPT testing with consistent ultrasound findings is also an exclusion.
4. Planned termination of the pregnancy
5. Parental unwillingness to participate in 1 year postnatal follow-up
6. Language barrier (non-English or Spanish speaking)

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes