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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to uncover the genetic causes of non-immune hydrops fetalis (NIHF) and other birth defects. Many cases of NIHF and similar conditions remain unexplained. Researchers use exome sequencing (a detailed genetic test) and trio exome sequencing (a genetic test involving the child and both parents) to find answers. The trial is open to those with pregnancies diagnosed with NIHF or other birth defects, including cases with chromosomal issues or post-birth samples. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to better understanding and potential solutions for these challenging conditions.

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 prior data suggests that exome sequencing is safe for genetic testing in fetuses?

Research has shown that exome sequencing is safe for studying genetic causes of fetal abnormalities. In reviewed studies, this method has been applied to many fetuses with various ultrasound findings, with no reports of harm or negative effects from the sequencing itself. This suggests the procedure is safe in this context.

Trio exome sequencing, which includes genetic information from the parents, has proven effective in diagnosing genetic conditions. Studies have not reported any safety concerns with this method either, indicating it is likely safe to use during pregnancy to help identify genetic issues.

Both exome sequencing and trio exome sequencing aid in understanding genetic conditions without posing a direct risk to the fetus. They analyze genetic information rather than involve physical procedures that could affect the baby. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about exome sequencing for detecting fetal abnormalities because it offers a deeper look into the genetic information of the fetus compared to standard tests like karyotyping or chromosomal microarray analysis. Exome sequencing specifically targets the coding regions of genes, which can help identify rare genetic mutations causing unexplained abnormalities. This method has the potential to provide more precise diagnoses, leading to better-informed decisions for expecting parents.

What evidence suggests that exome sequencing is effective for identifying genetic causes of non-immune hydrops fetalis?

Research has shown that exome sequencing, which participants in this trial will receive, can help identify genetic causes of birth defects. In one study, exome sequencing influenced decisions about pregnancy outcomes in 74% of cases. Another study found that exome sequencing successfully diagnosed up to 40.68% of certain fetal anomalies. Trio exome sequencing, which examines genes from both parents and the fetus, identified genetic issues in about 35.5% of cases with fetal structural problems. These findings suggest that exome sequencing is a powerful tool for understanding unexplained fetal abnormalities. ^{1 6 7 8 9}

Who Is on the Research Team?

Mary Norton, MD

Principal Investigator

University of California, San Francisco

Teresa Sparks, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9877148/

Prenatal Exome and Genome Sequencing for Fetal Structural ... This overview of prenatal sequencing includes information about indications for sequencing, methods, diagnostic yield, clinical utility, variant interpretation

2. genomemedicine.biomedcentral.com genomemedicine.biomedcentral.com/articles/10.1186/s13073-022-01130-x

Application of exome sequencing for prenatal diagnosis of ... In the prospective cohort, positive ES results contributed to decision making on termination or continuation of pregnancy in 74.0% of diagnostic ...

3. obgyn.onlinelibrary.wiley.com obgyn.onlinelibrary.wiley.com/doi/10.1002/pd.70006

Prenatal Exome Sequencing Analysis in Fetuses With ... The highest diagnostic yield was observed in the recurrent anomaly group (40.68%, 24/59), followed by the multisystem (28.41%, 25/88) and single ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5745303/

Promises, pitfalls and practicalities of prenatal whole exome ... Several small prenatal whole exome sequencing (WES) studies have successfully identified genetic diagnoses in fetuses with structural abnormalities when ...

5. tandfonline.com tandfonline.com/doi/full/10.1080/14767058.2025.2538208

Whole-exome sequencing for prenatal diagnosis of fetal ... Whole exome sequencing (WES) is a promising diagnostic tool for prenatal diagnosis. This study aimed to evaluate the efficiency of WES in identifying the ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0002929725001107

Advancing precision care in pregnancy through a treatable ... The use of genomic sequencing (GS) for prenatal diagnosis of fetuses with sonographic abnormalities has grown tremendously over the past decade.

7. nature.com nature.com/articles/s41431-021-01012-7

Singleton exome sequencing of 90 fetuses with ultrasound ... We present a retrospective study of 90 fetuses with different abnormal ultrasound findings, in which we employed the singleton exome sequencing ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12360300/

Application of family whole-exome sequencing for prenatal ... Translation of fertility risks through whole-exome sequencing of family lines to identify variants that explain patient's clinical ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT03482141

Clinical Utility of Prenatal Whole Exome Sequencing Whole exome sequencing (WES) will take place for prenatal patients (pregnancies with fetal structural defects). All patients will get exome sequencing and will ...