Genetic Testing for Fetal Abnormalities

(HyDROPS Trial)

Overseen By Dougherty Val, MS

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Disqualifiers: Monochorionic twins, Red cell alloimmunization

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

500 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a national, prospective study designed to investigate the genetic etiologies of non-immune hydrops fetalis (NIHF) and other birth defects. At least half of prenatally diagnosed NIHF cases remain of unknown etiology after standard work up, and a substantial proportion of other birth defects remain of unknown etiology as well. The investigators are performing exome sequencing (ES) for the affected fetus or neonate in unexplained cases, as well as enrolling cases with a genetic explanation to represent the full spectrum of diseases underlying NIHF and other birth defects.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Exome sequencing, Trio exome sequencing for fetal abnormalities?

Research shows that trio exome sequencing can help diagnose genetic issues in fetuses with structural anomalies when other tests like karyotype and microarray don't find anything. This means it can be a useful tool for understanding certain fetal abnormalities. ^{1 2 3 4 5}

Is genetic testing for fetal abnormalities safe for humans?

The research articles focus on the diagnostic performance and motivations for using exome sequencing in prenatal testing, but they do not provide specific safety data for humans. ^{1 2 3 5 6}

How does trio exome sequencing differ from other treatments for fetal abnormalities?

Trio exome sequencing is unique because it analyzes the genetic information of both parents and the fetus to identify potential genetic causes of fetal abnormalities, especially when other tests like karyotyping and microarray analysis show normal results. This approach can provide a more comprehensive understanding of genetic disorders, potentially influencing pregnancy management decisions. ^{1 2 3 7 8}

Research Team

Mary Norton, MD

Principal Investigator

University of California, San Francisco

Teresa Sparks, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for single or twin pregnancies diagnosed with non-immune hydrops fetalis (NIHF) or other birth defects, including those with chromosomal abnormalities, postnatal samples, and stillbirths. It excludes monochorionic twins and cases where hydrops is due to red cell alloimmunization.

Inclusion Criteria

My pregnancy involves NIHF or another birth defect, including cases with chromosomal abnormalities or stillbirths.

Exclusion Criteria

Monochorionic twin pregnancies and cases of hydrops fetalis attributed to red cell alloimmunization (due to hydrops fetalis caused by different pathophysiologic processes).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Exome Sequencing

Exome sequencing is performed for the affected fetus or neonate in unexplained cases of NIHF and other birth defects

2-4 weeks for ongoing pregnancies and live infants, 8-12 weeks for stillbirths, terminations, and infant demises

Data Collection

Clinical data is collected prospectively on all cases of NIHF and other birth defects, including demographics, medical and obstetric history, prenatal and delivery course, and postnatal outcomes

Follow-up

Participants are monitored for safety and effectiveness after exome sequencing and data collection

4 weeks

Treatment Details

Interventions

• Exome sequencing
• Trio exome sequencing

Trial Overview The study investigates the genetic causes of NIHF and other congenital anomalies by performing exome sequencing on affected fetuses or neonates whose conditions are unexplained after standard evaluations.

Participant Groups

Group I: Exome sequencing Experimental Treatment 1 Intervention

There is only one arm of this study. All enrolled participants with unexplained NIHF or other birth defect will be offered exome sequencing for the affected fetus or neonate. Please refer to the Study Design section for further details.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

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

Collaborator

Trials

2,103

Recruited

2,760,000+

Fetal Health Foundation

Collaborator

Trials

1

Recruited

500+

References

1. United States pubmed.ncbi.nlm.nih.gov

An approach to integrating exome sequencing for fetal structural anomalies into clinical practice. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Parental motivations for and adaptation to trio-exome sequencing in a prospective prenatal testing cohort: Beyond the diagnosis. [2022]

3. England pubmed.ncbi.nlm.nih.gov

A single center experience of prenatal parent-fetus trio exome sequencing for pregnancies with congenital anomalies. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Application of exome sequencing for prenatal diagnosis of fetal structural anomalies: clinical experience and lessons learned from a cohort of 1618 fetuses. [2022]

5. England pubmed.ncbi.nlm.nih.gov

High rate of abnormal findings in Prenatal Exome Trio in low risk pregnancies and apparently normal fetuses. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Lessons learnt from prenatal exome sequencing. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Prenatal diagnosis by trio exome sequencing in fetuses with ultrasound anomalies: A powerful diagnostic tool. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

Prenatal exome sequencing and chromosomal microarray analysis in fetal structural anomalies in a highly consanguineous population reveals a propensity of ciliopathy genes causing multisystem phenotypes. [2022]