Hydrops: Diagnosing & Redefining Outcomes With Precision Study (HyDROPS)

University of California San Francisco (UCSF)

Status: Active, not recruiting

Conditions: Fetal Anomaly; Hydrops Fetalis; Birth Defect

Treatments: Diagnostic Test: Exome sequencing

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03412760

5K12HD001262 (U.S. NIH Grant/Contract)

HydropsUCSF

Details and patient eligibility

About

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.

Full 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.

Enrollment: 500 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

500 participants in 1 patient group

Exome sequencing

Experimental group

Description:

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.

Treatment:

Diagnostic Test: Exome sequencing