title: Trisomy 13 detection in the first trimester of pregnancy using a chromosome-selective cell-free DNA analysis method.
abstract: OBJECTIVE
  To assess the performance of chromosome-selective sequencing of maternal plasma cell-free DNA (cfDNA) in non-invasive prenatal testing for trisomy 13.
  
  
  METHODS
  Two-phase case-control study on a single plasma sample per case. The first phase was used to optimize the trisomy 13 algorithm, which was then applied to a second dataset to determine the risk score for trisomy 13 by laboratory personnel who were blinded to the fetal karyotype.
  
  
  RESULTS
  In the first phase, trisomy 13 risk scores were given for 11 cases of trisomy 13 and 145 euploid cases at 11-13 weeks' gestation. The test identified seven (63.6%) cases of trisomy 13 with no false positives. The trisomy 13 algorithm was subsequently modified and the trisomy 13 risk score was > 99% in all 11 cases of trisomy 13 and < 0.01% in all 145 euploid cases. In the second phase, the new algorithm was used to generate trisomy 13 risk scores for 10 cases of trisomy 13 and 1939 euploid cases. The trisomy 13 risk scores were > 99% in eight (80.0% (95% confidence interval (CI), 49.0-94.3%)) cases of trisomy 13. In the 1939 euploid cases the risk score for trisomy 13 was < 0.01% in 1937 (99.9%), 0.79% in one, and > 99% in one. Therefore, at the predefined risk cut-off of 1% for classifying a sample as high or low risk, the false-positive rate (FPR) was 0.05% (95% CI, 0.0-0.3%).
  
  
  CONCLUSIONS
  Chromosome-selective sequencing of cfDNA can detect the majority of cases of trisomy 13 at an FPR of less than 0.1%.
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Ashoor
authors.forename: A
authors.initials: A
authors.lastname: Syngelaki
authors.forename: E
authors.initials: E
authors.lastname: Wang
authors.forename: C
authors.initials: C
authors.lastname: Struble
authors.forename: A
authors.initials: A
authors.lastname: Oliphant
authors.forename: K
authors.initials: K
authors.lastname: Song
authors.forename: K H
authors.initials: KH
authors.lastname: Nicolaides
mesh_terms: D000328:Adult; D000465:Algorithms; D016022:Case-Control Studies; D025063:Chromosome Disorders / Q000097:blood / Q000175:diagnosis*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D004247:DNA / Q000097:blood*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011296:Prenatal Diagnosis / Q000379:methods*; D018570:Risk Assessment / Q000379:methods; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods*; D014314:Trisomy / Q000175:diagnosis*; D000073839:Trisomy 13 Syndrome
chemical_list: D004247:DNA