Our research contributes novel information about genetic disorders that cause Non-Immune Hydrops Fetalis. This enables more accurate counseling, individualized antenatal care, and anticipation of neonatal needs.
What is hydrops?
Hydrops fetalis is a condition in pregnancy marked by abnormal collections of fluid in the developing fetus. There are two types of hydrops. One is immune in nature, and results from blood type incompatibility between the pregnant woman and fetus. The other type is non-immune, which comprises the vast majority of cases today and is the type of hydrops that we are studying. Non-immune hydrops fetalis (NIHF) can be caused by chromosomal abnormalities, single gene disorders, birth defects, infections, and other causes.
NIHF carries significant risks of stillbirth, early delivery, and serious illness and death for the newborn after birth. There is also risk to the pregnant woman of developing mirror syndrome, which may include high blood pressure, swelling, and damage to organs such as the kidneys and liver. These risks vary widely, however, by the underlying cause of the NIHF. Further, the approach to management of the pregnancy and treatment of the newborn after birth are largely dependent on establishing a clear cause for the NIHF.
What is our study about and why is it important?
Research by our group has shown that the underlying cause of NIHF remains unclear in at least half of all cases after standard testing. Further, genetic tests that are currently standard of care cannot detect the majority of genetic diseases that lead to NIHF. The HyDROPS study (Hydrops: Diagnosing and Redefining Outcomes with Precision Study) is focused on applying broad testing approaches to find the genetic causes of NIHF, as well as provide opportunities for more accurate counseling, individualized and improved care, and preparation for the needs of the infant such as treatments where available. Our team is dedicated to understanding what causes NIHF in each case in order to achieve these goals.
We are conducting a novel, prospective study to collect clinical data about NIHF cases, as well as to apply a broad genetic test called trio exome sequencing to discover the underlying genetic causes. Our research contributes important data about the types of genetic diseases leading to NIHF, as well as essential information to guide both the expectations of families and the care plans of providers. Ultimately, our goals are to develop a precision-based approach to care for NIHF to optimize survival and other outcomes, and ultimately, novel and targeted in utero treatments specific to each underlying cause.
Who can enroll in our study?
Inclusion criteria are one or more of the following:NIHF (two or more abnormal fluid collections in the fetus) Isolated abnormal fluid collections in the fetus (such as fluid only around the fetal lungs) Cystic hygroma Increased nuchal translucency measuring ≥ 3.5 mmCases that would not meet criteria for inclusion are those with hydrops resulting from alloimmunization or twin pregnancies with evidence of twin-twin transfusion syndrome.Participants may enroll either during pregnancy or after pregnancy. If genetic testing is not done until after birth, we can still enroll and plan to complete the testing after birth. We can enroll participants remotely over video or telephone, and travel to UCSF is not necessary for most cases.
- Diagnosis of NIHF
- Standard work up including amniocentesis or CVS during pregnancy, or diagnostic testing after birth
- Contact UCSF here or at any earlier time
- Samples to UCSF for trio exome sequencing (fetus or infant, and both biological parents)
- UCSF team returns results to the participant and referring provider
What happens if I enroll in the study?
For NIHF cases that are not clearly explained by standard genetic testing (karyotype or microarray), we offer trio exome sequencing through our UCSF Genomic Medicine Laboratory. Trio exome sequencing means that we sequence the full exome (~20,000 protein-coding genes) of the fetus or infant, and samples from each biological parent are used for reference. If samples from both biological parents are not available, then testing can also be done with a sample from only one parent.
We do return results of the exome sequencing to participants. For ongoing pregnancies or live infants, we return results in approximately 2-4 weeks. For non-continuing pregnancies, we return results in approximately 8-12 weeks. For each case, a multidisciplinary genetics and genomics panel at UCSF carefully reviews the findings of the testing and classifies genetic variants that are found. There is no cost to participating families for this testing.
What types of samples can be used for the exome sequencing?
Only one sample type is needed for the fetus or infant and for each biological parent:
- Fetus: cultured amniocytes, extracted DNA, cord blood, or other types of samples
- Infant: blood, buccal (cheek) swab, or other types of samples
- Parent: blood or saliva
Our team will assist with transferring all samples to UCSF to complete the testing. We can also ship saliva kits directly to participants’ homes with pre-paid return labels for easy return to our lab.
How can I participate?
If you would like to participate in the study or want more information, please either email our study team at [email protected] or call 1-800-RX-FETUS.
Where can I find out more about hydrops and exome sequencing?
For information on our recommended workup, download the Non-Immune Hydrops Fetalis Workup PDF
Fetal Exome Sequencing video
Fetal Exome Sequencing video (Spanish)
Fetal Exome Sequencing video (Mandarin)
Publications by our group
Mardy AH, Rangwala N, Hernandez-Cruz Y, Gosnell KA, Gonzalez JM, Norton ME, Sparks TN. Utility of chromosomal microarray for diagnosis in cases of nonimmune hydrops fetalis. Prenat Diagn 2020; Epub ahead of print. (PubMed)
Sparks TN, Thao K, Lianoglou BR, Boe NM, Bruce KG, Datkhaeva I, Field NT, Fratto VM, Jolley J, Laurent LC, Mardy AH, Murphy AM, Ngan E, Rangwala N, Rottkamp CAM, Wilson L, Wu E, Uy CC, Valdez Lopez P, Norton ME on behalf of the University of California Fetal-Maternal Consortium (UCfC). Nonimmune hydrops fetalis: identifying the underlying genetic etiology. Genet Med 2019; 21(6):1339-1344. (PubMed)
Mardy AH, Chetty SP, Norton ME, Sparks TN. A system-based approach to the genetic etiologies of non-immune hydrops fetalis. Prenat Diagn 2019; 39(9):732-750. (PubMed)
Berger VK, Sparks TN, Jelin AC, Derderian C, Jeanty C, Gosnell K, MacKenzie T, Gonzalez JM. Non-immune hydrops fetalis: Do placentomegaly and polyhydramnios matter? J Ultrasound Med 2018; 37(5):1185-1191. (PubMed)
Sparks TN, Lianoglou BR, Patel S, Adami R, Rangwala N, Datkhaeva I, Holliman K, Downum S, Amezcua J, Boe N, Laurent LC, MacKenzie TC, Murphy A, Sanders S, Slavotinek AM, Norton ME on behalf of the University of California Fetal-Maternal Consortium (UCfC). HyDROPS study: Exome sequencing identifies genetic disorders causing non-immune hydrops fetalis. Presented in oral format at: Annual Meeting of the Society for Maternal-Fetal Medicine (SMFM); Dallas, TX. February 3-8, 2020. (Abstract)
Sparks TN, Chen F, Lianoglou BR, Rego S, Patel S, Slavotinek AM, Koenig B, Norton ME. Agreement to secondary findings with exome sequencing in pre- and postnatal settings. Presented in poster format at: Annual Meeting of the Society for Maternal-Fetal Medicine (SMFM); Dallas, TX. February 3-8, 2020. (Abstract)
Mardy AH, Hernandez-Cruz Y, Rangwala N, Gosnell KA, Gonzalez JM, Norton ME, Sparks TN. Utility of chromosomal microarray in cases of non-immune hydrops fetalis. Poster presented at: Annual Meeting of the Society for Maternal-Fetal Medicine (SMFM); Las Vegas, NV. February 11-16, 2019. (Abstract)
Sparks TN, Thao K, Lianoglou B, Boe N, Bruce K, Datkaeva I, Field N, Fratto V, Jolley J, Laurent L, Mardy AH, Murphy AM, Rangwala N, Valdez Lopez P, Ngan E, Rottkamp C, Wilson L, Wu E, Uy C, Norton ME for University of California Fetal-Maternal Consortium. Underlying etiologies in prenatally-diagnosed non-immune hydrops fetalis. Poster presented at: Annual Meeting of the Society for Maternal-Fetal Medicine (SMFM); Dallas, TX. January 29-February 3, 2018. (Abstract)