Uncovering the Etiologies of Non-immune Hydrops Fetalis

NCT05528796 | Enrolling By Invitation FDA Device

• 1 other identifier: R01HD107190
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Non-immune hydrops fetalis (NIHF) is diagnosed on prenatal ultrasound when abnormal fluid collections are seen in the fetus. NIHF carries significant risks of stillbirth, preterm birth, and postnatal morbidity and mortality, particularly when the etiology remains unknown and critical opportunities for focused care and implementation of treatments are missed. In contrast, when an etiology is found, both pre- and postnatal management are directly impacted: counseling is focused, risks to the fetus and neonate are accurately anticipated, surveillance and in utero available treatments such as intrauterine transfusions are implemented, and postnatal treatments are promptly initiated to optimize outcomes. The overarching hypothesis is that discovering the precise etiologies of NIHF will create critical opportunities to improve outcomes through earlier, targeted pre- and postnatal care. Several important steps remain in order to uncover the genetic etiologies for cases remaining unsolved and improve care for these pregnancies. The study team proposes a multicenter collaboration to discover additional genetic diseases and novel variants underlying NIHF in a prospectively enrolled, large and diverse cohort utilizing whole genome sequencing (WGS) and RNA sequencing. The team will further perform comprehensive phenotyping to: a) collect detailed postnatal phenotypes and outcomes, b) re-analyze WGS data utilizing postnatal phenotype to identify diagnoses missed when sequencing algorithms incorporated only phenotype, and c) expand the phenotypes of all genetic in utero in utero diseases the investigators identify to optimize prenatal diagnosis and yield of genomic testing during pregnancy. Such a focused and comprehensive approach to the evaluation and diagnosis of NIHF has not previously been performed, particularly in a large and diverse cohort, and it is expected that this work will significantly improve the ability to understand and reshape the perinatal care for NIHF. This work will lay the foundation for redefining the approach to prenatal diagnosis, management, in utero and postnatal care for NIHF, and will create future opportunities to develop novel diagnostic algorithms and approaches to manage the complications of specific diseases underlying in utero NIHF.

Conditions

Non-Immune Hydrops Fetalis

Outcome Measures

Primary Outcomes (1)

• Number of cases for whom a genetic disease or novel variants were identified for underlying NIHF

  Cases with NIHF for whom pathogenic or likely pathogenic variants were identified implicating genetic disease

  1-3 months

Study Arms (1)

Pregnancies where the fetus has been diagnosed with NIHF

EXPERIMENTAL

The unit of analysis will be the "proband", i.e. pregnancy/fetus affected with non-immune hydrops fetalis (NIHF). Pregnant individuals receiving care at one of the participating sites whose fetus has been diagnosed with NIHF of unknown etiology will be eligible for recruitment and enrollment in this study. Biological fathers of the fetus with NIHF will also be enrolled when available in order to determine inheritance of fetal genetic variants when identified.

Diagnostic Test: Whole genome sequencing

Interventions

Whole genome sequencing DIAGNOSTIC_TEST

The investigators will study the genes in a fetus' or child's DNA using a test called genome sequencing. Genes are the instructions passed from individuals to a child, and genes determine how bodies are built and grow. Some medical conditions are caused by differences in genes, and the genome sequencing test looks for changes in genes and other parts of a person's genetic sequence (the genome). Genetic material will be extracted from bio-specimens. Genome sequencing for this study will be performed at the UCSF Genomic Medicine Laboratory at UCSF. When the genome sequencing results are available, the investigators will arrange an in person or telehealth meeting to explain the test results and what the results mean for the fetus, pregnancy, and family.

Pregnancies where the fetus has been diagnosed with NIHF

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Pregnant individuals whose fetus has been diagnosed with NIHF and standard prenatal testing with karyotype and/or microarray is non-diagnostic
• Neonates who received a prenatal diagnosis of NIHF, but genetic testing was unable to be completed or was deferred until after delivery

You may not qualify if:

• Fetuses/neonates with prenatal presentation of
• hydrops secondary to twin-twin transfusion syndrome,
• a clear viral etiology, or
• alloimmunization.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• University of California, San Diego: collaborator
• Albert Einstein College of Medicine: collaborator
• Johns Hopkins University: collaborator
• University of Pennsylvania: collaborator
• The Jackson Laboratory: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Hydrops Fetalis

Condition Hierarchy (Ancestors)

Erythroblastosis, Fetal; Fetal Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; alpha-Thalassemia; Thalassemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Immune System Diseases; Edema; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Teresa Sparks, MD

  UCSF Department of Obstetrics, Gynecology and Reproductive Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2022
• First Posted: September 6, 2022
• Study Start: March 1, 2022
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)