title: Validation of an Enhanced Version of a Single-Nucleotide Polymorphism-Based Noninvasive Prenatal Test for Detection of Fetal Aneuploidies.
abstract: OBJECTIVE
  To validate an updated version (Version 2) of a single-nucleotide polymorphism (SNP)-based noninvasive prenatal test (NIPT) and to determine the likelihood of success when testing for fetal aneuploidies following a redraw.
  
  
  METHODS
  Version 2 was analytically validated using 587 plasma samples with known genotype (184 trisomy 21, 37 trisomy 18, 15 trisomy 13, 9 monosomy X, 4 triploidy and 338 euploid). Sensitivity, specificity and no-call rate were calculated, and a fetal-fraction adjustment was applied to enable projection of these values in a commercial distribution. Likelihood of success of a second blood draw was computed based on fetal fraction and maternal weight from the first draw.
  
  
  RESULTS
  Validation of this methodology yielded high sensitivities (≥99.4%) and specificities (100%) for all conditions tested with an observed no-call rate of 2.3%. The no-call threshold for sample calling was reduced to 2.8% fetal fraction. The redraw success rate was driven by higher initial fetal fractions and lower maternal weights, with the fetal fraction being the more significant variable.
  
  
  CONCLUSIONS
  The enhanced version of this SNP-based NIPT method showed a reduced no-call rate and a reduced fetal-fraction threshold for sample calling in comparison to the earlier version, while maintaining high sensitivity and specificity.
authors.affiliation: Natera Inc., San Carlos, Calif., USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Ryan
authors.forename: Nathan
authors.initials: N
authors.lastname: Hunkapiller
authors.forename: Milena
authors.initials: M
authors.lastname: Banjevic
authors.forename: Naresh
authors.initials: N
authors.lastname: Vankayalapati
authors.forename: Nicole
authors.initials: N
authors.lastname: Fong
authors.forename: Kristine N
authors.initials: KN
authors.lastname: Jinnett
authors.forename: Zachary
authors.initials: Z
authors.lastname: Demko
authors.forename: Bernhard
authors.initials: B
authors.lastname: Zimmermann
authors.forename: Styrmir
authors.initials: S
authors.lastname: Sigurjonsson
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Gross
authors.forename: Matthew
authors.initials: M
authors.lastname: Hill
mesh_terms: D000328:Adult; D000782:Aneuploidy; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D005865:Gestational Age; D006801:Humans; D062145:Maternal Serum Screening Tests / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy