Birth Defect, Fetal Anomaly, Hydrops Fetalis
Conditions
Keywords
hydrops fetalis, birth defect, fetal anomaly, exome sequencing
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.
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: 1. Create registry of clinical data for cases of NIHF and other birth defects. 2. Investigate genetic variants underlying NIHF and other birth defects via ES. 3. 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.
Interventions
DIAGNOSTIC_TESTExome sequencing
Expansive genetic test performed for affected fetus or neonate.
Sponsors
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
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Genetic variants detected with exome sequencing that implicate a genetic disease underlying non-immune hydrops fetalis (NIHF) and other birth defects. | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORTeresa Sparks, MD, MAS
University of California, San Francisco
PRINCIPAL_INVESTIGATORMary Norton, MD
University of California, San Francisco
Outcome results
None listed