Sequencing Cell-Free DNA in the Maternal Circulation to Screen for Down Syndrome, Other Common Trisomies, and Selected Genetic Disorders

  • Glenn E. PalomakiEmail author
  • Robert G. Best


Up to three-quarters of pregnant women in the USA receive prenatal screening for Down syndrome (DS) and other fetal disorders. Historically, such testing has been based on combinations of maternal age, biochemical markers, and ultrasound findings with maximal detection rate for Down syndrome of 90% (sensitivity) at a false-positive rate of 2% (1-specificity) in a general pregnancy population. In 1997, a group from Hong Kong identified “fetal” cell-free (cf)DNA in maternal circulation. Unlike serum screening, cfDNA screening for Down syndrome is based directly on detection of extra chromosome 21 material from the fetal/placental unit. Following the 2011 publication of a prospective clinical trial of cfDNA, the first commercial prenatal screening test for Down syndrome based on circulating cfDNA was introduced into clinical practice. Among over 2000 DS and 200,000 euploid samples successfully tested, the detection rate for Down syndrome by a variety of cfDNA methods is presently over 99%, with a false-positive rate of about 0.2%. Multiple methodologies introduced by different laboratories have also shown detection rates at or above 95% for both trisomy 18 and trisomy 13. Occasionally (<1% to 5%), cfDNA testing fails to provide a usable results. Many of the commercial cfDNA tests also can identify the fetal sex as well as the common sex chromosome aneuploidies. This chapter discusses the use of cfDNA for the common autosomal trisomies, sex chromosome aneuploidies, microdeletions, nonviable chromosome disorders, emerging applications, technical limitations, emerging social and ethical issues, and areas for future study.


Cell-free (cf)DNA Sequencing Down syndrome Prenatal screening Trisomy Aneuploidy Sex chromosome aneuploidies Microdeletions Genetic testing Biomedical ethics Disruptive innovation Emerging technologies 


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Medical Screening and Special Testing, Department of Pathology and Laboratory MedicineWomen and Infants Hospital/Alpert Medical School of Brown UniversityProvidenceUSA
  2. 2.Savjani Institute for Health ResearchWindhamUSA
  3. 3.Biomedical SciencesUniversity of South Carolina School of Medicine/Greenville Health SystemGreenvilleUSA

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