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, at least half 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 are performing trio exome sequencing (ES) for the fetus or neonate (meaning that samples are collected from the fetus or neonate as well each each biological parent for reference) 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 are performing trio exome sequencing (ES) for the fetus or neonate (meaning that samples are collected from the fetus or neonate as well each each biological parent for reference) to investigate the underlying genetic etiology. This study is open for enrollment. Established collaborating sites include all five sites of the University of California Fetal-Maternal Consortium (UCfC). The UCfC 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 recruiting through these five centers, the investigators are also recruiting from ANY SITE NATIONALLY in order to develop a diverse cohort of NIHF cases and other birth defects. In addition to performing exome sequencing (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 until the infant is discharged from the hospital. The specific research aims include: 1. Create registry of 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 ES. 3. Develop a precision-based approach to antenatal and neonatal care in cases of 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, examining genotype-phenotype correlations will facilitate a precision-based approach to individualize counseling and also enable targeted neonatal (and in the future, antenatal) therapies such as enzyme replacement and stem cell transplantation.