Non-invasive Prenatal Screening for Fetal Aneuploidy: Comparison with Cytogenetic Results

Abstract

Non-invasive prenatal screening (NIPS) for fetal aneuploidy detection using cell-free fetal DNA from maternal circulation has been rapidly adopted for use in high-risk pregnancies since its inception in 2011. While most published NIPS studies are written from the clinical validation, obstetric, or technological viewpoints, in this review we summarize the published cytogenetics laboratory experience with this technology. A total of 528 NIPS positive cases were compared to cytogenetic results and the overall true-positive rate was 77 % (95 % CI 73.3-80.6) for all aneuploidies (407/528). Sixty percent (n = 317) showed increased risk for trisomy 21 and had a positive predictive value (PPV) of 92 % (95 % CI 88.2-94.6). The PPV for trisomy 18 was 69 % (95 % CI 59.3-78.1), 49 % (95 % CI 35.1-63.2) for trisomy 13, and 35 % (95 % CI 22.9-48.9) for combined sex chromosome abnormalities. This technology is rapidly expanding to include testing for microdeletion syndromes. In our limited experience with 18 cases referred to our laboratories after microdeletionpositive NIPS, only two were confirmed by cytogenetics, resulting in a PPV of 11 % (95 % CI 1.4-34.7). We discuss the reasons for discordant results which include confined placental mosaicism, vanishing co-twin, maternal mosaicism, maternal neoplasia, counting algorithms, and laboratory error.