Implementation of maternal blood cell-free DNA testing in early screening for aneuploidies

Ultrasound Obstet Gynecol. 2013 Jul;42(1):34-40. doi: 10.1002/uog.12504. Epub 2013 Jun 7.


Objective: To explore the feasibility of routine maternal blood cell-free (cf) DNA testing in screening for trisomies 21, 18 and 13 at 10 weeks' gestation.

Method: In this prospective study, women attending The Fetal Medicine Centre in London, UK, between October 2012 and April 2013, with singleton pregnancy and live fetus with CRL 32-45 mm, were screened for trisomies 21, 18 and 13 by cfDNA testing at 10 weeks and the combined test at 12 weeks.

Results: cfDNA testing was performed in 1005 singleton pregnancies with a median maternal age of 37 (range, 20-49) years. Risks for trisomies were provided for 957 (95.2%) cases and in 98.0% these were available within 14 days from sampling. In 48 (4.8%) cases no result was provided due to problems with delivery to the laboratory, low fetal fraction or assay failure. Repeat sampling was performed in 40 cases and a result obtained in 27 (67.5%) of these. In 11 cases the risk score for trisomy 21 and in five cases that for trisomy 18 was > 99%, in one the risk for trisomy 13 was 34% and in 968 the risk for each of the three trisomies was < 0.01%. The suspected trisomies were confirmed by karyotyping after chorionic villus sampling (CVS), except in one case of trisomy 18 in which the karyotype was normal. On the basis of the maternal age distribution of the study population, the expected and observed numbers for each of the three trisomies were similar. Both cfDNA and combined testing detected all trisomies, but the estimated false-positive rates (FPR) were 0.1% and 3.4%, respectively.

Conclusion: Routine screening for trisomies 21, 18 and 13 by cfDNA testing at 10 weeks is feasible and has a lower FPR than does combined testing, but abnormal results require confirmation by CVS.

Publication types

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

MeSH terms

  • Cell-Free System*
  • Chorionic Gonadotropin, beta Subunit, Human / metabolism
  • Chromosomes, Human, Pair 13*
  • Chromosomes, Human, Pair 18*
  • Chromosomes, Human, Pair 21*
  • Cytogenetic Analysis* / methods
  • DNA / blood*
  • DNA / genetics
  • Early Diagnosis
  • False Positive Reactions
  • Female
  • Genetic Counseling
  • Humans
  • London / epidemiology
  • Maternal Age
  • Nuchal Translucency Measurement / methods
  • Pregnancy
  • Pregnancy Trimester, First
  • Pregnancy-Associated Plasma Protein-A / metabolism
  • Prospective Studies
  • Risk Assessment
  • Sensitivity and Specificity
  • Trisomy / diagnosis*


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