title: Single-nucleotide polymorphism-based noninvasive prenatal screening in a high-risk and low-risk cohort.
abstract: 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<.001, odds ratio 9.2, CI 4.4-19.0). Sensitivity and specificity did not differ in low-risk and high-risk populations.
  
  
  CONCLUSIONS
  This noninvasive prenatal screen performed with high sensitivity and specificity in high-risk and low-risk cohorts. Aneuploid samples were significantly more likely to not return a result; the number of aneuploidy samples was especially increased among samples with low fetal fraction. This underscores the importance of redraws or, in rare cases, invasive procedures based on low fetal fraction.
  
  
  METHODS
  II.
authors.affiliation: Northwestern Reproductive Genetics, Chicago, Illinois; Columbia University, New York, New York; and Natera Inc, San Carlos, California.
authors.forename: Eugene
authors.initials: E
authors.lastname: Pergament
authors.forename: Howard
authors.initials: H
authors.lastname: Cuckle
authors.forename: Bernhard
authors.initials: B
authors.lastname: Zimmermann
authors.forename: Milena
authors.initials: M
authors.lastname: Banjevic
authors.forename: Styrmir
authors.initials: S
authors.lastname: Sigurjonsson
authors.forename: Allison
authors.initials: A
authors.lastname: Ryan
authors.forename: Megan P
authors.initials: MP
authors.lastname: Hall
authors.forename: Michael
authors.initials: M
authors.lastname: Dodd
authors.forename: Phil
authors.initials: P
authors.lastname: Lacroute
authors.forename: Melissa
authors.initials: M
authors.lastname: Stosic
authors.forename: Nikhil
authors.initials: N
authors.lastname: Chopra
authors.forename: Nathan
authors.initials: N
authors.lastname: Hunkapiller
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Prosen
authors.forename: Sallie
authors.initials: S
authors.lastname: McAdoo
authors.forename: Zachary
authors.initials: Z
authors.lastname: Demko
authors.forename: Asim
authors.initials: A
authors.lastname: Siddiqui
authors.forename: Matthew
authors.initials: M
authors.lastname: Hill
authors.forename: Matthew
authors.initials: M
authors.lastname: Rabinowitz
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D000782:Aneuploidy; D002474:Cell-Free System; D025063:Chromosome Disorders / Q000175:diagnosis*; D002882:Chromosomes, Human, Pair 13; D002887:Chromosomes, Human, Pair 18; D004247:DNA / Q000097:blood*; D004314:Down Syndrome / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014314:Trisomy / Q000175:diagnosis*; D000073839:Trisomy 13 Syndrome; D000073842:Trisomy 18 Syndrome; D014424:Turner Syndrome / Q000175:diagnosis*; D055815:Young Adult
chemical_list: D004247:DNA