Mammalian pregnancy involves tremendous de novo maternal vascular construction to adequately support conceptus development. In early mouse decidua basalis (DB), maternal uterine natural killer (uNK) cells oversee this process directing various aspects during the formation of supportive vascular networks. The uNK cells recruited to early implantation site DB secrete numerous factors that act in the construction of early decidual vessels (neoangiogenesis) as well as in the alteration of the structural components of newly developing and existing vessels (pruning and remodeling). Although decidual and placental development sufficient to support live births occur in the absence of normally functioning uNK cells, development and structure of implantation site are optimized through the presence of normally activated uNK cells. Human NK cells are also recruited to early decidua. Gestational complications including recurrent spontaneous abortion, fetal growth restriction, preeclampsia, and preterm labor are linked with the absence of human NK cell activation via paternally inherited conceptus transplantation antigens. This review summarizes the roles that mouse uNK cells normally play in decidual neoangiogenesis and spiral artery remodeling in mouse pregnancy and briefly discusses changes in early developmental angiogenesis due to placental growth factor deficiency.Reproduction (2015) 149 R91-R102

Whole exome sequencing (WES) is an integral tool in the diagnosis of genetic conditions in pediatric patients, but concerns have been expressed about the complexity of the information and the possibility for secondary findings that need to be conveyed to those deciding about WES. Currently, there is no validated tool to assess parental understanding of WES. We developed and implemented a survey to assess perceived and actual understanding of WES in parents who consented to clinical WES for their child between July 2013 and May 2015. Fifty-three eligible surveys were returned (57% response rate). Areas with both low perceived and actual understanding about WES included how genes are analyzed and lack of protection against life insurance discrimination. Parents also had low actual understanding for two questions related to secondary findings - reporting of secondary findings in a parent (if tested) and whether secondary findings can be related to traits such as height and hair color. Further work to develop a validated tool to assess understanding of WES would be beneficial as WES is integrated more frequently into clinical care.

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Purpose: To characterize the genetic testing ordered, diagnoses made, and charges acquired for patients admitted to a level IV Neonatal Intensive Care Unit (NICU) in 2013 and 2014. Methods: Retrospective chart review of all patients admitted to a single level IV NICU in 2013 and 2014. Demographic, genetic testing, genetic diagnosis, and charge data were collected from the electronic medical record (EMR). Results: A total of 1327 unique patients were admitted to our level IV NICU during the study period. During the NICU stay and up to two years of age, 478 genetic tests were ordered for 276 (20.8%) patients. Of these, 73.4% (351) were ordered during the initial NICU admission. Most patients had only one test ordered, though this ranged from one to seven tests. The most commonly ordered test in the NICU was a microarray (103, 29.3%), which was the confirmatory test for 12.6% of those patients with a diagnoses. The least commonly ordered test was whole exome sequencing (4, 1.1%). A genetic diagnosis was made in 36.3% of patients who had genetic testing. In total, 128 patients (9.6%) received a genetic diagnosis by two years through genetic testing or other means. These patients were significantly more likely to be either term or late preterm (p = 0.0025), and to have normal birth weights (p = 0.0111). Inpatient clinical genetics evaluation improved the rate of diagnosis as opposed to performing genetic testing without a clinical genetics evaluation (26.5% vs. 44.5% in patients with a consult). However, a majority of the diagnoses (57.6%) were made after discharge. Of the 265 (20.0% of cohort) patients who received a genetics consult, 83 (31.3%) received a diagnosis. Patients receiving a diagnosis had significantly longer and more costly hospital stays. They had higher genetics charges, as expected. These patients were also more labor intensive than patients without a genetic diagnosis. In total $851,982 in charges for genetics services were accrued during the two year study window, equaling $642.04 per patient when averaged across the study cohort. Conclusions: Our study characterized the genetic evaluation, testing, and diagnoses of a level IV NICU cohort over a two year time period. Nearly 10% of our cohort received a genetic iii diagnosis by two years of age. These patients had longer NICU stays, more costly stays, and required more work to care for them than their counterparts without a genetic diagnosis. Inpatient genetic consultations increased the rate of diagnosis in patients and despite overall more costly stays, genetics charges-for hospital and physician charges and testing-were very low relative to the overall cost of their NICU stay across the cohort.