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

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ClinicalTrials.gov Identifier: NCT03412760

Recruitment Status : Enrolling by invitation

First Posted : January 26, 2018

Last Update Posted : January 10, 2023

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborators:

National Institutes of Health (NIH)

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

Fetal Health Foundation

Information provided by (Responsible Party):

University of California, San Francisco

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hydrops Fetalis Birth Defect Fetal Anomaly	Diagnostic Test: Exome sequencing	Not Applicable

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:

Create registry of clinical data for cases of NIHF and other birth defects.
Investigate genetic variants underlying NIHF and other birth defects via ES.
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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	500 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Intervention Model Description:	All cases of unexplained non-immune hydrops fetalis (NIHF) or other birth defects enrolled in the study will be offered exome sequencing (ES) for the affected fetus or neonate.
Masking:	None (Open Label)
Primary Purpose:	Diagnostic
Official Title:	Hydrops: Diagnosing & Redefining Outcomes With Precision Study
Actual Study Start Date :	October 11, 2018
Estimated Primary Completion Date :	November 2025
Estimated Study Completion Date :	December 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Edema

Genetic and Rare Diseases Information Center resources: Hydrops Fetalis Thalassemia Alpha-thalassemia

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Diagnostic Test: Exome sequencing Expansive genetic test performed for affected fetus or neonate.

Outcome Measures

Primary Outcome Measures :

Genetic variants detected with exome sequencing that implicate a genetic disease underlying non-immune hydrops fetalis (NIHF) and other birth defects. [ Time Frame: Turn around time for exome sequencing results is 2-4 weeks for ongoing pregnancies and live infants, and is 8-12 weeks for stillbirths, terminations, and infant demises. ]
Both NIHF and birth defects can be caused by a variety of genetic variants that researchers are continuing to learn more about. Exome sequencing will yield information about the specific genetic variants present in cases of NIHF and other birth defects, and about the specific diseases implicated by these variants. Investigators will determine the proportion of cases seen in the setting of particular genetic variants, and will correlate phenotypic outcomes with specific genotypes.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 55 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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).

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03412760

Locations

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United States, California
University of California, San Francisco
San Francisco, California, United States, 94143

Sponsors and Collaborators

University of California, San Francisco

National Institutes of Health (NIH)

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

Fetal Health Foundation

Investigators

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Principal Investigator:	Teresa Sparks, MD, MAS	University of California, San Francisco
Principal Investigator:	Mary Norton, MD	University of California, San Francisco

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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Responsible Party:	University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT03412760
Other Study ID Numbers:	HydropsUCSF 5K12HD001262 ( U.S. NIH Grant/Contract )
First Posted:	January 26, 2018 Key Record Dates
Last Update Posted:	January 10, 2023
Last Verified:	January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No
Plan Description:	De-identified data will be shared only in accordance with NIH/NICHD regulations as the Women's Reproductive Health Research (WRHR) grant is a funding source for this study, and is co-sponsored by these bodies.

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	Yes
Device Product Not Approved or Cleared by U.S. FDA:	Yes
Product Manufactured in and Exported from the U.S.:	No

Keywords provided by University of California, San Francisco:


hydrops fetalis birth defect fetal anomaly exome sequencing

Additional relevant MeSH terms:

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Hydrops Fetalis Congenital Abnormalities Edema Erythroblastosis, Fetal Fetal Diseases Pregnancy Complications Female Urogenital Diseases and Pregnancy Complications	Urogenital Diseases Hematologic Diseases alpha-Thalassemia Thalassemia Hemoglobinopathies Genetic Diseases, Inborn Immune System Diseases

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