Hydrops FetalisHyDROPSNCT03412760
Hydrops: Diagnosing & Redefining Outcomes With Precision Study
A study testing Exome sequencing in people with Hydrops Fetalis and Birth Defect, run by University of California, San Francisco at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Hydrops Fetalis, Birth Defect, Fetal Anomaly
- What is being tested?
- Exome sequencing
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Oct 2018to Feb 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
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.
Read the 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.
- Conditions
- Hydrops Fetalis, Birth Defect, Fetal Anomaly
- Being tested
- Exome sequencing
- Keywords
- hydrops fetalis, birth defect, fetal anomaly, exome sequencing
- Medical subject headings
- Hydrops Fetalis, Congenital Abnormalities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exome sequencingDiagnostic test
Expansive genetic test performed for affected fetus or neonate.
| Study group | Role | What they receive |
|---|---|---|
| Exome sequencing | Experimental | 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. Receives: Diagnostic Test: Exome sequencing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Genetic variants detected with exome sequencing that implicate a genetic disease underlying non-immune hydrops fetalis (NIHF) and other birth defects.
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2018
- Study start11 Oct 2018
- Primary completionDec 2026 (estimated)
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hydrops FetalisStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Fetal Health Foundation
- Responsible party
- Sponsor
- Investigators
- Teresa Sparks, MD, MAS, Principal investigator, University of California, San FranciscoMary Norton, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03412760
- Sponsor's protocol ID
- HydropsUCSF
- Other IDs
- 5K12HD001262
- Acronym
- HyDROPS
- Status last verified
- Apr 2026
- First submitted
- 10 Jan 2018
- Last updated
- 17 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: 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.
Publications
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.
PubMed 33027564
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hydrops: Diagnosing & Redefining Outcomes With Precision Study
- ClinicalTrials.gov ID
- NCT03412760
- Acronym / sponsor ID
- HyDROPS / HydropsUCSF
- Conditions
- Hydrops Fetalis, Birth Defect, Fetal Anomaly
- Keywords
- hydrops fetalis, birth defect, fetal anomaly, exome sequencing
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Fetal Health Foundation
- Study start
- 11 Oct 2018 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Feb 2027 (estimated)
- First posted
- 26 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Exome sequencing | Experimental | Diagnostic Test: Exome sequencingThere 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- Monochorionic twin pregnancies and cases of hydrops fetalis that are attributed to red cell alloimmunization (due to hydrops fetalis caused by different pathophysiologic processes).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exome sequencingExpansive genetic test performed for affected fetus or neonate. | Diagnostic test | Exome sequencing |
Primary outcome
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2026.
- Derived from this study: PubMed 33027564Sparks 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.
- Individual participant dataSharing planned: No. 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.
Related trials for Hydrops Fetalis
Enrolling by invitation
Uncovering the Etiologies of Non-immune Hydrops Fetalis
Non-Immune Hydrops Fetalis
RecruitingObservational study
Fetal Electrophysiologic Abnormalities in High-Risk Pregnancies Associated With Fetal Demise
High Risk Pregnancy, Congenital Heart Disease
Recruiting
In-utero Hematopoietic Stem Cell Transplantation for the Treatment of Fetuses With Bart's Hydrops Fetalis Syndrome
Haemoglobin Barts Hydrops
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Teresa Sparks, MD, MAS principal investigator
University of California, San Francisco
Mary Norton, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exome sequencing in people with Hydrops Fetalis and Birth Defect, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 17 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03412760, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2026.