Fetal Birth Defects: Toward a Precision-based Approach
| Status: | Recruiting |
|---|---|
| Conditions: | Cardiology, Women's Studies |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Reproductive |
| Healthy: | No |
| Age Range: | 18 - 55 |
| Updated: | 10/14/2018 |
| Start Date: | October 11, 2018 |
| End Date: | December 2025 |
| Contact: | Teresa Sparks, MD |
| Email: | teresa.sparks@ucsf.edu |
| Phone: | 415-514-9399 |
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, up to 46%
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 will perform whole exome sequencing (WES) for the fetus or neonate, as well as
both biological parents, in each of these cases to investigate the underlying genetic
etiology.
non-immune hydrops fetalis (NIHF) and other birth defects. In the setting of NIHF, up to 46%
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 will perform whole exome sequencing (WES) for the fetus or neonate, as well as
both biological parents, in each of these cases to investigate the underlying genetic
etiology.
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 will perform whole exome sequencing (WES) for the
fetus or neonate, as well as both biological parents, in each of these cases to investigate
the underlying genetic etiology.
Currently, this study is IRB-approved at UCSF and enrollment is anticipated to begin by
November 2018. Moving forward, the investigators are expanding IRB approval through the UC
Reliance in order to include all sites of the University of California Fetal-Maternal
Consortium (UCfC), which 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 performing trio whole exome sequencing (WES), the investigators
will also collect 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 a multi-center registry to collect 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 whole exome
sequencing (WES).
3. Develop a precision-based approach to antenatal and neonatal care in cases of NIHF and
other birth defects by i) understanding not only the type of disease process, but also
the implications of a particular genotype, and ii) improving the ability to predict
prognosis, counsel patients, and tailor antenatal and postnatal management.
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 again individualize counseling and
also enable targeted neonatal (and in the future, antenatal) therapies such as enzyme
replacement and stem cell transplantation. The NIH has recognized the importance of such a
precision-based approach to medical care.
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 will perform whole exome sequencing (WES) for the
fetus or neonate, as well as both biological parents, in each of these cases to investigate
the underlying genetic etiology.
Currently, this study is IRB-approved at UCSF and enrollment is anticipated to begin by
November 2018. Moving forward, the investigators are expanding IRB approval through the UC
Reliance in order to include all sites of the University of California Fetal-Maternal
Consortium (UCfC), which 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 performing trio whole exome sequencing (WES), the investigators
will also collect 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 a multi-center registry to collect 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 whole exome
sequencing (WES).
3. Develop a precision-based approach to antenatal and neonatal care in cases of NIHF and
other birth defects by i) understanding not only the type of disease process, but also
the implications of a particular genotype, and ii) improving the ability to predict
prognosis, counsel patients, and tailor antenatal and postnatal management.
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 again individualize counseling and
also enable targeted neonatal (and in the future, antenatal) therapies such as enzyme
replacement and stem cell transplantation. The NIH has recognized the importance of such a
precision-based approach to medical care.
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).
We found this trial at
1
site
San Francisco, California 94143
Principal Investigator: Teresa Sparks, MD
Phone: 415-514-9399
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