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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03412760
Recruitment Status : Recruiting
First Posted : January 26, 2018
Last Update Posted : April 10, 2020
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
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Brief Summary:
This is a multi-center, prospective study designed to investigate the genetic etiologies of non-immune hydrops fetalis (NIHF) and other birth defects. In the setting of NIHF, at least half of prenatally diagnosed 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 trio exome sequencing (ES) for the fetus or neonate (meaning that samples are collected from the fetus or neonate as well each each biological parent for reference) to investigate the underlying genetic etiology.

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

Detailed Description:

Between 1:1700 and 1:3000 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 trio exome sequencing (ES) for the fetus or neonate (meaning that samples are collected from the fetus or neonate as well each each biological parent for reference) to investigate the underlying genetic etiology.

This study is open for enrollment. Established collaborating sites include all five sites of the University of California Fetal-Maternal Consortium (UCfC). The UCfC is a collaborative network of investigators with representatives from five UC medical centers (UC Davis, UC Irvine, UC Los Angeles, UC San Diego, UC San Francisco). In addition to recruiting through these five centers, the investigators are also recruiting from ANY SITE NATIONALLY in order to develop a diverse cohort of NIHF cases and other birth defects.

In addition to performing exome sequencing (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 until the infant is discharged from the hospital.

The specific research aims include:

  1. Create registry of clinical data for cases of non-immune hydrops fetalis (NIHF) and other birth defects.
  2. Investigate the genetic variants underlying NIHF and other birth defects via ES.

  3. Develop a precision-based approach to antenatal and neonatal care in cases of 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, examining genotype-phenotype correlations will facilitate a precision-based approach to individualize counseling and also enable targeted neonatal (and in the future, antenatal) therapies such as enzyme replacement and stem cell transplantation.

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 non-immune hydrops fetalis (NIHF) or other birth defects enrolled in the study will be offered trio exome sequencing (ES). This will be trio ES ideally, meaning that ES will be offered for the affected fetus as well as for both of the biologic parents. If one or both of the parents are unavailable, then duo or proband-only ES could be done, respectively.
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

Arms and Interventions
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Arm Intervention/treatment
Experimental: Trio exome sequencing
There is only one arm of this study. All enrolled participants will be offered trio exome sequencing (or duo where necessary). Please refer to the Study Design section for further details.
 Diagnostic Test: Trio exome sequencing
Expansive genetic test performed for affected fetus as well as for both biological parents where possible (or for only one parent where applicable).


Outcome Measures
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Primary Outcome Measures :
  1. Genetic variants detected on exome sequencing that implicate a cause of 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 8-10 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
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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
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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


Contacts
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Contact: Teresa Sparks, MD 415-514-9399 hydrops@ucsf.edu
Contact: Dougherty Val, MS 415-514-0730 dougherv@ucsf.edu

Locations
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United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Teresa Sparks, MD    415-514-9399    hydrops@ucsf.edu   
Contact: Dougherty Val, MS    415-514-0730    dougherv@ucsf.edu   
Principal Investigator: Teresa Sparks, MD         
Principal Investigator: Mary Norton, MD         
Sub-Investigator: Billie Lianoglou, LCGC         
Sub-Investigator: Tippi Mackenzie, MD         
Sub-Investigator: Stephan Sanders, MD, PhD         
Sub-Investigator: Ophir Klein, MD, PhD         
Sub-Investigator: Renata Gallagher, MD, PhD         
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 University of California, San Francisco
Principal Investigator: Mary Norton, MD University of California, San Francisco
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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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: April 10, 2020
Last Verified: April 2020
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
whole exome sequencing
Additional relevant MeSH terms:
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Hydrops Fetalis
Congenital Abnormalities
Edema
Erythroblastosis, Fetal
Fetal Diseases
Pregnancy Complications
 Hematologic Diseases
alpha-Thalassemia
Thalassemia
Hemoglobinopathies
Genetic Diseases, Inborn
Immune System Diseases