Hydrops: Diagnosing & Redefining Outcomes With Precision Study

NCT ID: NCT03412760

Last Updated: 2026-02-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-11
• Study Completion Date: 2027-02-28

Brief Summary

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.

Detailed Description

Up to 1:1700 pregnancies are affected by non-immune hydrops fetalis (NIHF), and this condition is associated with significant perinatal risks ranging from preterm birth to Ballantyne (maternal mirror) syndrome, stillbirth, and neonatal death. Birth defects affect 1:33 pregnancies, and are the leading cause of infant death (contributing to approximately 20% of infant deaths). 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.

This study is open for enrollment by invitation. In addition to performing ES, the investigators are collecting clinical data prospectively on all cases of NIHF and other birth defects, including demographics, medical and obstetric history, prenatal and delivery course, and postnatal outcomes.

The specific research aims include:

1. Create registry of clinical data for cases of NIHF and other birth defects.

2. Investigate genetic variants underlying NIHF and other birth defects via ES.

3. Characterize the features and outcomes of genetic diseases presenting with NIHF and other birth defects.

• In particular, the researchers are focused on enrolling cases of increased nuchal translucency, cystic hygroma, abnormal fetal fluid collection (even single fluid compartments such as isolated pleural effusion), and/or frank NIHF.

This research will contribute novel information about the frequency and types of genetic disorders in fetuses and newborns with a diagnosis of NIHF and other birth defects, enabling providers to more accurately counsel about prognosis and individualize perinatal care. This information will also facilitate informed decision-making for parents, allow the care team to anticipate specific perinatal needs, and enable more precise counseling for the parents about recurrence risks for NIHF and other birth defects. Further, the research will facilitate future aims such as novel fetal therapies for genetic diseases.

Conditions

Hydrops Fetalis; Birth Defect; Fetal Anomaly

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Exome sequencing

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.

Group Type: EXPERIMENTAL

Exome sequencing

Intervention Type: DIAGNOSTIC_TEST

Expansive genetic test performed for affected fetus or neonate.

Interventions

Exome sequencing

Expansive genetic test performed for affected fetus or neonate.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Singletons or dichorionic twin pregnancies that are diagnosed prenatally with non-immune hydrops fetalis (NIHF) or another birth defect. Cases with chromosomal abnormalities, postnatal samples, and stillbirths will still be included.

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

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

NIH

Sponsor Role: collaborator

Fetal Health Foundation

UNKNOWN

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Teresa Sparks, MD, MAS

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Mary Norton, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California, San Francisco

San Francisco, California, United States

Countries

United States

References

Sparks TN, Lianoglou BR, Adami RR, Pluym ID, Holliman K, Duffy J, Downum SL, Patel S, Faubel A, Boe NM, Field NT, Murphy A, Laurent LC, Jolley J, Uy C, Slavotinek AM, Devine P, Hodoglugil U, Van Ziffle J, Sanders SJ, MacKenzie TC, Norton ME; University of California Fetal-Maternal Consortium; University of California, San Francisco Center for Maternal-Fetal Precision Medicine. Exome Sequencing for Prenatal Diagnosis in Nonimmune Hydrops Fetalis. N Engl J Med. 2020 Oct 29;383(18):1746-1756. doi: 10.1056/NEJMoa2023643. Epub 2020 Oct 7.

Reference Type: DERIVED

PMID: 33027564 (View on PubMed)

Other Identifiers

5K12HD001262

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HydropsUCSF

Identifier Type: -

Identifier Source: org_study_id