for people ages 18-55 (full criteria)
at San Francisco, California
study started
estimated completion
Teresa Sparks Mary Norton



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.


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.


Hydrops FetalisBirth DefectFetal Anomalywhole exome sequencingCongenital AbnormalitiesEdemaTrio whole exome sequencing


You can join if…

Open to people ages 18-55

  • 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.

You CAN'T join if...

  • Monochorionic twin pregnancies and cases of hydrops fetalis that are attributed to red cell alloimmunization (due to hydrops fetalis caused by different pathophysiologic processes).


  • University of California, San Franciscoaccepting new patients
    San FranciscoCalifornia94143United States

Lead Scientists

  • Teresa Sparks
    I am an obstetrician specializing in Maternal-Fetal Medicine and Clinical Genetics. In my practice, I care for women who are either pregnant or considering pregnancy, including those with pregnancies that are higher risk for a variety of reasons. Teaching and mentoring are activities that I take very seriously, and see as an essential part of my very day job.
  • Mary Norton
    Authored (or co-authored) 123 research publications


accepting new patients
Start Date
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University of California, San Francisco
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