Nonimmune hydrops fetalis: identifying the underlying genetic etiology.

PURPOSE: Numerous etiologies may lead to nonimmune hydrops fetalis (NIHF), and the underlying cause often remains unclear. We aimed to determine the proportion of NIHF cases in which the etiology was clearly determined in a large, contemporary, and diverse cohort, as well as to describe the etiologies with a focus on genetic causes. METHODS: Retrospective review of NIHF cases between 2015 and 2017 from the five University of California Fetal-Maternal Consortium sites. Singleton pregnancies with prenatally diagnosed NIHF were included, and cases with maternal alloimmunization were excluded. Cases were categorized as being of confirmed, suspected, or unknown etiology. RESULTS: Sixty-five NIHF cases were identified. Forty-six percent (30/65) remained of unknown etiology, while 9.2% (6/65) had a suspected etiology and 44.6% (29/65) were of confirmed etiology. Among confirmed cases, 11 resulted from aneuploidy; 7 from fetal structural anomalies; 2 each from fetal arrhythmia, Noonan syndrome, and generalized lymphatic dysplasia; and 1 each from arthrogryposis, parvovirus, neonatal alloimmune thrombocytopenia, fetal goiter, and Kasabach-Merritt syndrome. CONCLUSION: In this contemporary, multicenter study, the cause of prenatally diagnosed NIHF was confirmed in only 44% of cases, and a genetic etiology was found in only 25% of those that received standard of care genetic testing.

Mosaic trisomy 16: what are the obstetric and long-term childhood outcomes?

PURPOSE: To evaluate obstetric and neonatal outcomes as well as long-term neurodevelopmental outcomes and quality of life among prenatally detected cases of mosaic trisomy (MT16) and confined placental mosaicism (CPM) for trisomy 16. METHODS: We recruited participants for this cross-sectional study through an international registry of families with children diagnosed with MT16 or CPM. Parents were interviewed about expectations based on prenatal counseling as well as about actual perinatal outcomes, congenital anomalies, medical conditions, and school progress. Health-related quality of life (HRQOL) was assessed via the Pediatric Quality of Life Inventory 4.0 Generic Core Scales. RESULTS: Forty-four families were enrolled, and 68.2% of the children were female. Common complications were gestational hypertension (gHTN) or preeclampsia (38.1%), preterm delivery (PTD; 71.4%), cesarean delivery (CD; 73.8%), birth weight <10th percentile (73.8%), neonatal intensive care unit (NICU) admission (88.1%), and congenital anomalies (59.5%). However, 81.8% of school-aged children were entirely in mainstream classes, and median physical, psychosocial, and total HRQOL scores were high: 90.6 (34.4-100), 86.7 (35-100), and 84.8 (34.8-100), respectively (100 = optimal quality of life). CONCLUSION: Several obstetric and neonatal complications are common with pregnancies affected by MT16 or CPM. However, the majority of children demonstrate normal neurodevelopmental outcomes and high HRQOL.Genet Med advance online publication 06 April 2017.

Preferences regarding contemporary prenatal genetic tests among women desiring testing: implications for optimal testing strategies.

OBJECTIVES: To compare utilities for prenatal testing outcomes among women inclined to continue their pregnancy despite abnormal results versus those inclined to terminate and to analyze how differences affect optimal prenatal testing strategies. METHOD: Time tradeoff utilities for 23 outcomes were elicited from 281 women. We compared utilities based on termination inclination and applied them to a decision-analytic framework. RESULTS: Of participants, 46.6% indicated that they would 'definitely' or 'probably' continue their pregnancy despite results indicating an intellectual disability. These women assigned higher utilities to abnormal testing results and having a child with an intellectual disability than women who would probably or definitely terminate. Primary cell-free DNA screening had the most quality-adjusted life years for women inclined to continue their pregnancy but yielded an incremental cost-effectiveness ratio (ICER) of $1 685 449. Multiple marker screening with either cell-free DNA or diagnostic testing as follow-up had an ICER of $9037. Primary diagnostic testing resulted in the most quality-adjusted life years for women inclined to terminate, with an ICER of $111 776. CONCLUSION: Women seeking testing vary in prenatal testing outcome preferences and termination inclinations in the context of results indicating an intellectual disability. How they envision utilizing prenatal testing information impacts their optimal testing strategy. © 2016 John Wiley & Sons, Ltd.

Their Last Breath: Death and Dying in a Hmong American Community.

Hmong Americans have typically been unwilling to use biomedical palliative care for end-of-life needs. This has resulted in confusion and frustration for Hmong patients, families, and nurses. Hmongs' end-of-life care choices for family members usually involve in-home caregiving provided by the family using a combination of biomedicine and traditional healing methods. Health care decisions are made for the patient by the family and community in this familistic culture. A qualitative approach was used to explore the beliefs that ultimately determine end-of-life care goals and strategies for Hmong patients. Semistructured interviews were conducted with 15 family caregivers of terminally ill patients and 5 shamans and Hmong funeral officiants. Several themes affecting care choices were identified, including cultural legacies of the responsibility of end-of-life caregiving by the family, the desire for family privacy in caregiving, and the role of community in the care for the dying, as well as completion of the rituals that ensure the soul of the deceased reaches the afterlife. Suggestions for improving communication between Hmongs and biomedical providers include providing information about end-of-life care beliefs and strategies to biomedical care providers and providing information to Hmong patients and families about hospice and palliative care options and services to support family care.

100K Pathogen Genome Project: 306 Listeria Draft Genome Sequences for Food Safety and Public Health.

Listeria monocytogenes is a food-associated bacterium that is responsible for food-related illnesses worldwide. This is the initial public release of 306 L. monocytogenes genome sequences as part of the 100K Pathogen Genome Project. These isolates represent global genomic diversity in L. monocytogenes.

Automation of PacBio SMRTbell NGS library preparation for bacterial genome sequencing.

BACKGROUND: The PacBio RS II provides for single molecule, real-time DNA technology to sequence genomes and detect DNA modifications. The starting point for high-quality sequence production is high molecular weight genomic DNA. To automate the library preparation process, there must be high-throughput methods in place to assess the genomic DNA, to ensure the size and amounts of the sheared DNA fragments and final library. FINDINGS: The library construction automation was accomplished using the Agilent NGS workstation with Bravo accessories for heating, shaking, cooling, and magnetic bead manipulations for template purification. The quality control methods from gDNA input to final library using the Agilent Bioanalyzer System and Agilent TapeStation System were evaluated. CONCLUSIONS: Automated protocols of PacBio 10 kb library preparation produced libraries with similar technical performance to those generated manually. The TapeStation System proved to be a reliable method that could be used in a 96-well plate format to QC the DNA equivalent to the standard Bioanalyzer System results. The DNA Integrity Number that is calculated in the TapeStation System software upon analysis of genomic DNA is quite helpful to assure that the starting genomic DNA is not degraded. In this respect, the gDNA assay on the TapeStation System is preferable to the DNA 12000 assay on the Bioanalyzer System, which cannot run genomic DNA, nor can the Bioanalyzer work directly from the 96-well plates.

Draft Genome Sequences of 1,183 Salmonella Strains from the 100K Pathogen Genome Project.

Salmonella is a common food-associated bacterium that has substantial impact on worldwide human health and the global economy. This is the public release of 1,183 Salmonella draft genome sequences as part of the 100K Pathogen Genome Project. These isolates represent global genomic diversity in the Salmonella genus.

Genetic dissection of epidermal growth factor receptor signaling during luteinizing hormone-induced oocyte maturation.

Recent evidence that luteinizing hormone (LH) stimulation of ovulatory follicles causes transactivation of the epidermal growth factor receptor (EGFR) has provided insights into the mechanisms of ovulation. However, the complete array of signals that promote oocyte reentry into the meiotic cell cycle in the follicle are still incompletely understood. To elucidate the signaling downstream of EGFR involved in oocyte maturation, we have investigated the LH responses in granulosa cells with targeted ablation of EGFR. Oocyte maturation and ovulation is disrupted when EGFR expression is progressively reduced. In granulosa cells from mice with either global or granulosa cell-specific disruption of EGFR signaling, LH-induced phosphorylation of MAPK3/1, p38MAPK, and connexin-43 is impaired. Although the LH-induced decrease in cGMP is EGFR-dependent in wild type follicles, LH still induces a decrease in cGMP in Egfr(delta/f) Cyp19-Cre follicles. Thus compensatory mechanisms appear activated in the mutant. Spatial propagation of the LH signal in the follicle also is dependent on the EGF network, and likely is important for the control of signaling to the oocyte. Thus, multiple signals and redundant pathways contribute to regulating oocyte reentry into the cell cycle.