J. Clin. Med.2014, 3(3), 849-864; doi:10.3390/jcm3030849 - published online 24 July 2014 Show/Hide Abstract
Abstract: Until recently, maternal serum analyte levels paired with sonographic fetal nuchal translucency measurement was the most accurate prenatal screen available for Trisomies 18 and 21, (91% and 94% detection and false positive rates of 0.31% and 4.5% respectively). Women with positive California Prenatal Screening Program (CPSP) results have the option of diagnostic testing to determine definitively if the fetus has a chromosomal abnormality. Cell-free fetal (cff-) DNA screening for Trisomies 13, 18, and 21 was first offered in 2012, allowing women with positive screens to choose additional screening before diagnostic testing. Cff-DNA sensitivity rates are as high as 99.9% and 99.1%, with false positive rates of 0.4% and 0.1%, for Trisomies 18 and 21, respectively. A retrospective chart review was performed in 2012 on 500 CPSP referrals at the University of California, San Diego Thornton Hospital. Data were collected prior to and after the introduction of cff-DNA. There was a significant increase in the number of participants who chose to pursue additional testing and a decrease in the number of invasive procedures performed after cff-DNA screening was available. We conclude that as fetal aneuploidy screening improves, the number of invasive procedures will continue to decrease.
J. Clin. Med.2014, 3(3), 838-848; doi:10.3390/jcm3030838 - published online 24 July 2014 Show/Hide Abstract
Abstract: This report describes the trends of chorionic villus sampling (CVS) referred for prenatal genetic diagnosis in the past two and a half decades in a Portuguese Center. Our cohort of 491 CVS was mostly performed by the transcervical method at the 12th gestational week. Data collected within the framework of this study relate to the following: sampling method, referral reason versus abnormality and incidence of procedure-related pregnancy loss, that declined to about 0.5% over the last 15 years. The year 2000 represented a change in referral reasons for chorionic tissue collection, shifting from almost exclusively for cytogenetic testing to an increasing number of molecular tests for monogenic disorders. Herein, success rates as well as cytogenetic and/or molecular DNA results are presented. These latter include not only tests for several monogenic disorders, but also aneuploidy and maternal cell contamination screening. This retrospective analysis reiterates that CVS is a safe and reliable first trimester technique for prenatal diagnosis in high genetic risk pregnancies.
J. Clin. Med.2014, 3(3), 809-837; doi:10.3390/jcm3030809 - published online 24 July 2014 Show/Hide Abstract
Abstract: Chromosomal mosaicism is one of the primary interpretative issues in prenatal diagnosis. In this review, the mechanisms underlying feto-placental chromosomal mosaicism are presented. Based on the substantial retrospective diagnostic experience with chorionic villi samples (CVS) of a prenatal diagnosis laboratory the following items are discussed: (i) The frequency of the different types of mosaicism (confined placental, CPM, and true fetal mosaicisms, TFM); (ii) The risk of fetal confirmation after the detection of a mosaic in CVS stratified by chromosome abnormality and placental tissue involvement; (iii) The frequency of uniparental disomy for imprinted chromosomes associated with CPM; (iv) The incidence of false-positive and false-negative results in CVS samples analyzed by only (semi-)direct preparation or long term culture; and (v) The implications of the presence of a feto-placental mosaicism for microarray analysis of CVS and non-invasive prenatal screening (NIPS).
J. Clin. Med.2014, 3(3), 795-808; doi:10.3390/jcm3030795 - published online 17 July 2014 Show/Hide Abstract
Abstract: Obesity is a worldwide epidemic and can have a profound effect on pregnancy risks. Obese patients tend to be older and are at increased risk for structural fetal anomalies and aneuploidy, making screening options critically important for these women. Failure rates for first-trimester nuchal translucency (NT) screening increase with obesity, while the ability to detect soft-markers declines, limiting ultrasound-based screening options. Obesity also decreases the chances of completing the anatomy survey and increases the residual risk of undetected anomalies. Additionally, non-invasive prenatal testing (NIPT) is less likely to provide an informative result in obese patients. Understanding the limitations and diagnostic accuracy of aneuploidy and anomaly screening in obese patients can help guide clinicians in counseling patients on the screening options.
J. Clin. Med.2014, 3(3), 763-794; doi:10.3390/jcm3030763 - published online 15 July 2014 Show/Hide Abstract
Abstract: In recent years, the obesity epidemic has developed into a major health crisis both in the United States as well as throughout the developed world. With current treatments limited to expensive, high-risk surgery and minimally efficacious pharmacotherapy, new therapeutic options are urgently needed to combat this alarming trend. This review focuses on the endogenous gut-brain signaling axes that regulate appetite under physiological conditions, and discusses their clinical relevance by summarizing the clinical and preclinical studies that have investigated manipulation of these pathways to treat obesity.
J. Clin. Med.2014, 3(3), 747-762; doi:10.3390/jcm3030747 - published online 8 July 2014 Show/Hide Abstract
Abstract: Prenatal diagnostic testing is a rapidly advancing field. An accurate diagnosis of structural anomalies and additional abnormalities in fetuses with structural anomalies is important to allow “triage” and designation of prognosis. This will allow parents to make an informed decision relating to the pregnancy. This review outlines the current tests used in prenatal diagnosis, focusing particularly on “new technologies” such as exome sequencing. We demonstrate the utility of exome sequencing above that of conventional karyotyping and Chromosomal Microarray (CMA) alone by outlining a recent proof of concept study investigating 30 parent-fetus trios where the fetus is known to have a structural anomaly. This may allow the identification of pathological gene anomalies and consequently improved prognostic profiling, as well as excluding anomalies and distinguishing between de novo and inherited mutations, in order to estimate the recurrence risk in future pregnancies. The potential ethical dilemmas surrounding exome sequencing are also considered, and the future of prenatal genetic diagnosis is discussed.