Single-Nucleotide Polymorphism–Based Noninvasive Prenatal Screening in a High-Risk and Low-Risk Cohort

OBJECTIVE:To estimate performance of a single-nucleotide polymorphism–based noninvasive prenatal screen for fetal aneuploidy in high-risk and low-risk populations on single venopuncture. METHODS:One thousand sixty-four maternal blood samples from 7 weeks of gestation and beyond were included; 1,051 were within specifications and 518 (49.3%) were low risk. Cell-free DNA was amplified, sequenced, and analyzed using the Next-generation Aneuploidy Test Using SNPs algorithm. Samples were called as trisomies 21, 18, 13, or monosomy X, or euploid, and male or female. RESULTS:Nine hundred sixty-six samples (91.9%) successfully generated a cell-free DNA result. Among these, sensitivity was 100% for trisomy 21 (58/58, confidence interval [CI] 93.8–100%), trisomy 13 (12/12, CI 73.5–100%), and fetal sex (358/358 female, CI 99.0–100%; 418/418 male, CI 99.1–100%), 96.0% for trisomy 18 (24/25, CI 79.7–99.9%), and 90% for monosomy X (9/10, CI 55.5–99.8%). Specificity for trisomies 21 and 13 was 100% (905/905, CI 99.6–100%; and 953/953, CI 99.6–100%, respectively) and for trisomy 18 and monosomy X was 99.9% (938/939, CI 99.4–100%; and 953/954, CI 99.4–100%, respectively). However, 16% (20/125) of aneuploid samples did not return a result; 50% (10/20) had a fetal fraction below the 1.5th percentile of euploid pregnancies. Aneuploidy rate was significantly higher in these samples (P