title: Clinical experience and follow-up with large scale single-nucleotide polymorphism-based noninvasive prenatal aneuploidy testing.
abstract: OBJECTIVE
  We sought to report on laboratory and clinical experience following 6 months of clinical implementation of a single-nucleotide polymorphism-based noninvasive prenatal aneuploidy test in high- and low-risk women.
  
  
  METHODS
  All samples received from March through September 2013 and drawn ≥9 weeks' gestation were included. Samples that passed quality control were analyzed for trisomy 21, trisomy 18, trisomy 13, and monosomy X. Results were reported as high or low risk for fetal aneuploidy for each interrogated chromosome. Relationships between fetal fraction and gestational age and maternal weight were analyzed. Follow-up on outcome was sought for a subset of high-risk cases. False-negative results were reported voluntarily by providers. Positive predictive value (PPV) was calculated from cases with an available prenatal or postnatal karyotype or clinical evaluation at birth.
  
  
  RESULTS
  Samples were received from 31,030 patients, 30,705 met study criteria, and 28,739 passed quality-control metrics and received a report detailing aneuploidy risk. Fetal fraction correlated positively with gestational age, and negatively with maternal weight. In all, 507 patients received a high-risk result for any of the 4 tested conditions (324 trisomy 21, 82 trisomy 18, 41 trisomy 13, 61 monosomy X; including 1 double aneuploidy case). Within the 17,885 cases included in follow-up analysis, 356 were high risk, and outcome information revealed 184 (51.7%) true positives, 38 (10.7%) false positives, 19 (5.3%) with ultrasound findings suggestive of aneuploidy, 36 (10.1%) spontaneous abortions without karyotype confirmation, 22 (6.2%) terminations without karyotype confirmation, and 57 (16.0%) lost to follow-up. This yielded an 82.9% PPV for all aneuploidies, and a 90.9% PPV for trisomy 21. The overall PPV for women aged ≥35 years was similar to the PPV for women aged <35 years. Two patients were reported as false negatives.
  
  
  CONCLUSIONS
  The data from this large-scale report on clinical application of a commercially available noninvasive prenatal test suggest that the clinical performance of this single-nucleotide polymorphism-based noninvasive prenatal test in a mixed high- and low-risk population is consistent with performance in validation studies.
authors.affiliation: Division of Fetal Medicine, Department of Obstetrics and Gynecology and Women's Health, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Pe'er
authors.initials: P
authors.lastname: Dar
authors.affiliation: Natera Inc, San Carlos, CA.
authors.forename: Kirsten J
authors.initials: KJ
authors.lastname: Curnow
authors.affiliation: Natera Inc, San Carlos, CA.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Gross
authors.affiliation: Natera Inc, San Carlos, CA.
authors.forename: Megan P
authors.initials: MP
authors.lastname: Hall
authors.affiliation: Natera Inc, San Carlos, CA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Stosic
authors.affiliation: Natera Inc, San Carlos, CA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Demko
authors.affiliation: Natera Inc, San Carlos, CA.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Zimmermann
authors.affiliation: Natera Inc, San Carlos, CA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hill
authors.affiliation: Natera Inc, San Carlos, CA.
authors.forename: Styrmir
authors.initials: S
authors.lastname: Sigurjonsson
authors.affiliation: Natera Inc, San Carlos, CA.
authors.forename: Allison
authors.initials: A
authors.lastname: Ryan
authors.affiliation: Natera Inc, San Carlos, CA.
authors.forename: Milena
authors.initials: M
authors.lastname: Banjevic
authors.affiliation: Quest Diagnostics, Nichols Institute, San Juan Capistrano, CA.
authors.forename: Paula L
authors.initials: PL
authors.lastname: Kolacki
authors.affiliation: Quest Diagnostics, Nichols Institute, San Juan Capistrano, CA.
authors.forename: Susan W
authors.initials: SW
authors.lastname: Koch
authors.affiliation: Quest Diagnostics, Nichols Institute, San Juan Capistrano, CA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Strom
authors.affiliation: Natera Inc, San Carlos, CA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Rabinowitz
authors.affiliation: Division of Human Genetics, Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT. Electronic address: benn@nso1.uchc.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Benn
mesh_terms: D000293:Adolescent; D000328:Adult; D000782:Aneuploidy; D001835:Body Weight; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D004247:DNA / Q000097:blood / Q000235:genetics*; D004314:Down Syndrome / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012189:Retrospective Studies; D014314:Trisomy / Q000175:diagnosis* / Q000235:genetics; D000073839:Trisomy 13 Syndrome; D000073842:Trisomy 18 Syndrome; D014424:Turner Syndrome / Q000175:diagnosis* / Q000235:genetics; D055815:Young Adult
chemical_list: D004247:DNA
keywords: low-risk; noninvasive prenatal testing; single-nucleotide polymorphism; trisomy 21