Uncovering the Etiologies of Non-immune Hydrops Fetalis

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

Interventions

DIAGNOSTIC_TEST

Whole genome sequencing

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.

Sponsors & Collaborators

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

  collaborator NIH

• University of California, San Diego

  collaborator OTHER

• Albert Einstein College of Medicine

  collaborator OTHER

• Johns Hopkins University

  collaborator OTHER

• University of Pennsylvania

  collaborator OTHER

• The Jackson Laboratory

  collaborator OTHER

• University of California, San Francisco

  lead OTHER

Principal Investigators

• Teresa Sparks, MD · UCSF Department of Obstetrics, Gynecology and Reproductive Sciences

Study Design

Allocation

NA

Purpose

DIAGNOSTIC

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-03-01

Primary Completion

2027-02-28

Completion

2027-02-28

FDA Device

Yes

Countries

• United States

Study Locations