title: Cell-Free DNA Screening: Complexities and Challenges of Clinical Implementation.
abstract: Screening for fetal aneuploidy in pregnant women using cell-free DNA has increased dramatically since the technology became commercially available in 2011. Since that time, numerous trials have demonstrated high sensitivity and specificity to screen for common aneuploidies in high-risk populations. Studies assessing the performance of these tests in low-risk populations have also demonstrated improved detection rates compared with traditional, serum-based screening strategies. Concurrent with the increased use of this technology has been a decrease in invasive procedures (amniocentesis and chorionic villus sampling). As the technology becomes more widely understood, available, and utilized, challenges regarding its clinical implementation have become apparent. Some of these challenges include test failures, false-positive and false-negative results, limitations in positive predictive value in low-prevalence populations, and potential maternal health implications of abnormal results. In addition, commercial laboratories are expanding screening beyond common aneuploidies to include microdeletion screening and whole genome screening. This review article is intended to provide the practicing obstetrician with a summary of the complexities of cell-free DNA screening and the challenges of implementing it in the clinical setting.
authors.affiliation: Clinical Fellow.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Grace
authors.affiliation: Clinical Instructor and Certified Genetic Counselor, Prenatal Diagnosis Program.
authors.forename: Emily
authors.initials: E
authors.lastname: Hardisty
authors.affiliation: Clinical Fellow.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Dotters-Katz
authors.affiliation: Assistant Professor and Director of Reproductive Genetics, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC.
authors.forename: Neeta L
authors.initials: NL
authors.lastname: Vora
authors.affiliation: Professor, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Duke University, Durham, NC.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kuller
mesh_terms: D000782:Aneuploidy; D015415:Biomarkers / Q000097:blood; D004247:DNA / Q000097:blood*; D004314:Down Syndrome / Q000175:diagnosis; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008423:Maternal Age; D062145:Maternal Serum Screening Tests / Q000379:methods*; D017410:Practice Guidelines as Topic; D011237:Predictive Value of Tests; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood; D011296:Prenatal Diagnosis / Q000379:methods*
chemical_list: D015415:Biomarkers; D004247:DNA