An observational study in Nonimmune Fetal Hydrops, Nonimmune Hydrops in Neonate and Genetic Disorders, sponsored by Thomas Jefferson University. Completed at 1 site in United States. Open to participants aged 16 Years to 55 Years. Per ClinicalTrials.gov, last updated 2026-07-14.
Sponsored by Thomas Jefferson University · Observational
Brief Summary: Nonimmune hydrops fetalis (NIHF) is a potentially fatal condition characterized by abnormal fluid accumulation in two or more fetal compartments. Numerous etiologies may lead to NIHF, and the underlying cause often remains unclear (1). The current standard of genetic diagnostic testing includes a fetal karyotype and chromosomal microarray (CMA), with an option to pursue single gene testing on amniocytes collected by amniocentesis (2). A large subgroup of the NIHF causes includes single gene disorders that are not diagnosed with the standard genetic workup for hydrops. Currently, nearly 1 in 5 cases of NIHF is defined as idiopathic, meaning there is no identified etiology (2). The investigators believe this is because the causes of NIHF are not completely investigated, specifically single gene disorders. Our research study aims to increase the diagnostic yield by performing whole exome sequencing (WES) and whole genome sequencing (WGS) on prenatal and neonatal NIHF cases when standard genetic testing is negative, identifying known and new genes, thus providing vital information to families regarding the specific diagnosis and risk to future pregnancies. The investigators plan to perform WES as the initial diagnostic test. If WES is negative, then the investigators will proceed to perform WGS.
This is a prospective cohort study design for fetuses or neonates affected with NIHF. Mother-father-fetus trios of pregnancies complicated by idiopathic non-immune fetal hydrops will be identified. These patients will be counseled by a Maternal-Fetal Medicine specialist as would be the routine. As part of the routine work-up, amniocentesis will be recommended for karyotype, CMA and an infectious work-up. Amniocentesis will be performed by the Maternal-Fetal Medicine specialist of the referring institution. The patient will also be offered genetic counseling (routine). Subjects will be offered enrollment when inclusion criteria are met. After enrollment, the following samples will be collected: (1) maternal blood (2) paternal blood, (3) fetal DNA isolated from amniocytes (4) neonatal blood when referral is done postnatally. The WES results will be reported to the genetic counselor dedicated to the study. The parents will be contacted by the genetic counselor and counseled on the findings whether they were positive or negative. The result will also be communicated to the patient's primary MFM provider or pediatrician and appropriate referrals to pediatric genetics specialists will be made by the primary provider. In cases where no genetic disorder is identified, the sample will be stored and then subsequently whole genome sequencing will be performed.
403 studies on the registry are indexed under Genetic Diseases, Inborn; 145 are open to participants now.
This study's enrollment of 55 is below the median of 192 across 195 observational studies indexed under Genetic Diseases, Inborn.
Browse Genetic Diseases, Inborn studies →Thomas Jefferson University is the lead sponsor of 384 studies on the registry; 71 are open to participants now.
Of its 44 completed or terminated interventional studies of FDA-regulated products, 20 (45%) have results posted.
Counted across the registry records on this site, refreshed daily.
Patients will be recruited from MFM physicians, paediatricians,and neonatologists.
The following inclusion criteria will apply:
The following exclusion criteria will apply:
DNA obtained from amniotic fluid samples
Diagnostic Test: Whole Exome Sequencing · Diagnostic Test: Whole Genome Sequencing
DNA obtained from neonatal blood samples
Diagnostic Test: Whole Exome Sequencing · Diagnostic Test: Whole Genome Sequencing
Whole exome sequencing (WES) provides more detailed information through greater resolution, identifying single base-pair changes and small insertions and deletions. WES performs sequencing on the protein-coding exons, which are contained in 1-2% of the genome but make up over 85% of all known pathogenic mutations.
Whole Genome Sequencing (WGS) has emerged in recent years as a diagnostic tool that sequences the entire genome and can pick up insertions or deletion of bases, structural variants and intronic single nucleotide variations.
Identify known single gene disorders that would not be detected by microarray as a cause of nonimmune fetal hydrops by performing whole exome sequencing (WES)
Time frame: 5 years
Identify novel genetic disorders associated with nonimmune hydrops
Time frame: 5 years
Evaluate the incremental value of whole genome sequencing (WGS) in the evaluation of fetal hydrops when WES is negative
Time frame: 5 years
Better counsel the parents about the etiology of hydrops especially if they desire a subsequent pregnancy
Time frame: 5 years
Plan to share: Yes
This study is completed, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Thomas Jefferson University