title: First-trimester contingent screening for trisomies 21, 18 and 13 by biomarkers and maternal blood cell-free DNA testing.
abstract: OBJECTIVE
  To examine potential performance of screening for trisomies by cell-free (cf) DNA testing in maternal blood contingent on results of first-line testing by combinations of fetal translucency thickness (NT), fetal heart rate (FHR), ductus venosus pulsatility index (DV PIV), and serum-free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PLGF) and α-fetoprotein (AFP).
  
  
  METHODS
  Performance was estimated for firstly, screening by cfDNA in all pregnancies and secondly, cfDNA testing contingent on results of first-line testing by combinations of ultrasound and biochemical markers.
  
  
  RESULTS
  In first-line screening by cfDNA testing, the detection rate for trisomy 21 and trisomies 18 or 13 would be 99 and 96%, respectively, after invasive testing in 1% of the population. In contingent screening, a detection rate of 98% for trisomy 21 and 96% for trisomy 18 or 13, at an invasive testing rate of 0.7%, can be achieved by carrying out cfDNA testing in about 35, 20 and 11% of cases identified by first-line screening with the combined test alone (age, NT, FHR, β-hCG, PAPP-A), the combined test plus PLGF and AFP and the combined test plus PLGF, AFP and DV PIV, respectively.
  
  
  CONCLUSIONS
  Effective first-trimester screening for trisomies can be achieved by contingent screening incorporating biomarkers and cfDNA testing.
authors.affiliation: Harris Birthright Research Centre of Fetal Medicine, King's College Hospital, London, UK.
authors.forename: K H
authors.initials: KH
authors.lastname: Nicolaides
authors.forename: A
authors.initials: A
authors.lastname: Syngelaki
authors.forename: L C
authors.initials: LC
authors.lastname: Poon
authors.forename: M M
authors.initials: MM
authors.lastname: Gil
authors.forename: D
authors.initials: D
authors.lastname: Wright
mesh_terms: D015415:Biomarkers / Q000097:blood; D002474:Cell-Free System / Q000502:physiology; D025063:Chromosome Disorders / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004314:Down Syndrome / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D062145:Maternal Serum Screening Tests / Q000379:methods / Q000592:standards*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood / Q000235:genetics*; D014314:Trisomy / Q000175:diagnosis / Q000235:genetics*; D000073839:Trisomy 13 Syndrome; D000073842:Trisomy 18 Syndrome
chemical_list: D015415:Biomarkers; D004247:DNA