First-trimester contingent screening for trisomies 21, 18 and 13 by biomarkers and maternal blood cell-free DNA testing

Fetal Diagn Ther. 2014;35(3):185-92. doi: 10.1159/000356066. Epub 2013 Oct 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Cell-Free System / physiology
  • Chromosome Disorders / blood
  • Chromosome Disorders / diagnosis
  • Chromosome Disorders / genetics*
  • Chromosomes, Human, Pair 13 / genetics
  • Chromosomes, Human, Pair 18 / genetics
  • Chromosomes, Human, Pair 18 / metabolism
  • DNA / genetics*
  • Down Syndrome / blood
  • Down Syndrome / diagnosis
  • Down Syndrome / genetics*
  • Female
  • Humans
  • Maternal Serum Screening Tests / methods
  • Maternal Serum Screening Tests / standards*
  • Pregnancy
  • Pregnancy Trimester, First / blood
  • Pregnancy Trimester, First / genetics*
  • Trisomy / diagnosis
  • Trisomy / genetics*
  • Trisomy 13 Syndrome
  • Trisomy 18 Syndrome


  • Biomarkers
  • DNA