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.
Obstetricians and gynecologists, family physicians.
After completing this activity, the learner should be better able to understand the complexities of cell-free DNA screening and describe considerations involved in its clinical implementation.
*Clinical Fellow, †Clinical Instructor and Certified Genetic Counselor, Prenatal Diagnosis Program, and ‡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; and §Professor, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Duke University, Durham, NC
All authors and staff in a position to control the content of this CME activity and their spouses/life partners (if any) have disclosed that they have no financial relationships with, or financial interests in, any commercial organizations pertaining to this educational activity.
Correspondence requests to: Matthew R. Grace, MD, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, 3010 Old Clinic Bldg, Campus Box 7516, Chapel Hill, NC 27599-7516. E-mail: email@example.com.