Cell-free DNA Testing: Where are We now?

Abstract

ABSTRACTPrenatal screening for fetal aneuploidies has been focused on mainly Down syndrome in the last 40 years. The method of screening has changed from maternal age in the 1970s, with a detection rate of 30 and 5% false positive rate (FPR), to a combination of maternal age and second-trimester serum biochemical markers (triple test and quadruple test) in the 1980s and 1990s, with 60 to 75% detection rate and 5% false positive rate (FPR). Following this, the era of first trimester screening for Down syndrome has started with the clinical implementation of fetal nuchal translucency screening. The combination of maternal age, NT thickness and serum free beta-human chorionic gonadotropin (â-hCG) and pregnancy-associated plasma protein A (PAPP-A) in the first trimester has yielded a 90% detection rate with a 5% FPR. Starting from the year 2008, studies have shown that the performance of screening may be improved by analysis of cell-free deoxyribonucleic acid (DNA) (cfDNA) in maternal blood. Several studies in the last few years have reported the clinical validation of cell free fetal DNA test in the maternal serum in screening for trisomies 21, 18, and 13 and sex chromosome aneuploidies.Its widespread use is limited by the relatively high cost of the test and the lack of consensus about the optimal way for its clinical implementation. Until the optimal way of incorporating cfDNA into the clinical practice gets identified, it would be wise not to substitute cfDNA testing in place of first-trimester screening for fetal defects and other major complications of pregnancy. Furthermore, it would be preferable for clinicians managing individual patients not to counsel them for their result as positive or negative, rather the clinicians should use the risk estimate from the first-line method of screening as the prior risk and modify this by the appropriate positive or negative likelihood ratio from the cfDNA test.How to cite this articleSen C, Api O, Yayla M, Goynumer G. Cell-free DNA Testing: Where are We now? Donald School J Ultrasound Obstet Gynecol 2016;10(2):172-177.