First-trimester contingent screening for trisomy 21 by biomarkers and maternal blood cell-free DNA testing

Ultrasound Obstet Gynecol. 2013 Jul;42(1):41-50. doi: 10.1002/uog.12511. Epub 2013 Jun 7.


Objective: To define risk cut-offs with corresponding detection rates (DR) and false-positive rates (FPR) in screening for trisomy 21 using maternal age and combinations of first-trimester biomarkers in order to determine which women should undergo contingent maternal blood cell-free (cf) DNA testing.

Methods: From singleton pregnancies undergoing screening for aneuploidies at three UK hospitals between March 2006 and May 2012, we analyzed prospectively collected data on the following biomarkers: fetal nuchal translucency thickness (NT) and ductus venosus pulsatility index for veins (DV-PIV) at 11 + 0 to 13 + 6 weeks' gestation and serum free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PlGF) and alpha-fetoprotein (AFP) at 8 + 0 to 13 + 6 weeks. Estimates of risk cut-offs, DRs and FPRs were derived for combinations of biomarkers and these were used to define the best strategy for contingent cfDNA testing.

Results: In contingent screening, detection of 98% of fetuses with trisomy 21 at an overall invasive testing rate < 0.5% can be potentially achieved by offering cfDNA testing to about 36%, 21% and 11% of cases identified by first-line screening using the combined test alone, using the combined test with the addition of serum PlGF and AFP and using the combined test with the addition of PlGF, AFP and DV-PIV, respectively.

Conclusions: Effective first-trimester screening for trisomy 21, with DR of 98% and invasive testing rate < 0.5%, can be potentially achieved by contingent screening incorporating biomarkers and cfDNA testing.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Cell-Free System*
  • Chorionic Gonadotropin, beta Subunit, Human / metabolism*
  • Cytogenetic Analysis* / methods
  • DNA / blood*
  • DNA / genetics
  • Down Syndrome / diagnosis*
  • Female
  • Humans
  • Maternal Age
  • Nuchal Translucency Measurement / methods
  • Pregnancy
  • Pregnancy Trimester, First*
  • Pregnancy-Associated Plasma Protein-A / metabolism*
  • Prenatal Diagnosis
  • Prospective Studies
  • Surveys and Questionnaires
  • Time Factors
  • United Kingdom / epidemiology


  • Biomarkers
  • Chorionic Gonadotropin, beta Subunit, Human
  • DNA
  • Pregnancy-Associated Plasma Protein-A