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Adherence of cell-free DNA noninvasive prenatal screens to ACMG recommendations



Noninvasive prenatal screening (NIPS) for fetal aneuploidy via cell-free DNA has been commercially available in the United States since 2011. In 2016, the American College of Medical Genetics and Genomics (ACMG) issued a position statement with specific recommendations for testing laboratories. We sought to evaluate adherence to these recommendations.


We focused on commercial laboratories performing NIPS testing in the United States as of 1 January 2018. Sample laboratory reports and other materials were scored for compliance with ACMG recommendations. Variables scored for common and sex chromosome aneuploidy detection included detection rate, specificity, positive and negative predictive value, and fetal fraction. Labs that performed analysis of copy-number variants and results for aneuploidies other than those commonly reported were identified. Available patient education materials were similarly evaluated.


Nine of 10 companies reported fetal fraction in their reports, and 8 of 10 did not offer screening for autosomal aneuploidies beyond trisomy 13, 18, and 21. There was inconsistency in the application and reporting of other measures recommended by ACMG.


Laboratories varied in the degree to which they met ACMG position statement recommendations. No company adhered to all laboratory guidance.

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The authors would like to thank Judith Benkendorf for her early assistance with this research.

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Financial conflicts of interest: B.G.S. occasionally consults on the topic of Down syndrome (DS) through Gerson Lehrman Group. He receives remuneration from DS nonprofit organizations for speaking engagements and associated travel expenses. B.G.S. receives annual royalties from Woodbine House, Inc., for the publication of his book, Fasten Your Seatbelt: A Crash Course on Down Syndrome for Brothers and Sisters. Within the past 2 years, B.G.S. has received research funding from F. Hoffmann–La Roche, Inc. to conduct clinical trials on study drugs for people with DS. B.G.S. is occasionally asked to serve as an expert witness for legal cases where DS is discussed. M.W.L. and S.M. are employees of the National Center for Prenatal & Postnatal Resources at the University of Kentucky, which produces and sells patient educational material recommended by professional guidelines; M.W.L. and S.M. receive no direct compensation from the sale of such materials. K.B. has financial holdings in GenomeSmart, a patient education platform. M.A.A. is an employee of Mayo Clinic, which provides cell-free DNA testing services through Mayo Medical Laboratories; M.A.A. receives no direct compensation from the sale of such tests. A.R.G. participated in the production of a continuing medical education (CME) activity on NIPT for Medscape. Other conflicts of interest: Beyond the items mentioned in the financial disclosures above, B.G.S. serves in a nonpaid capacity on the Honorary Board of Directors for the Massachusetts Down Syndrome Congress, the Board of Directors for the Band of Angels Foundation, and the Professional Advisory Committee for the National Center for Prenatal and Postnatal Down Syndrome Resources. B.G.S. has a sister with DS. M.W.L. serves in a nonpaid capacity on the D.S. Education Foundation for Down Syndrome of Louisville. M.W.L. has a daughter with DS. S.M. has a son with DS. S.K. and A.R.G. serve in a nonpaid capacity on the Board of Directors for the American College of Medical Genetics and Genomics (ACMG). A.R.G. also serves on the ACMG Foundation Board of Directors. M.A.A. has received travel funding compensation from the Association for X and Y Chromosome Variations. The other authors declare no conflicts of interest.

Correspondence to Brian G. Skotko MD, MPP.

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  • noninvasive prenatal tests
  • NIPT
  • noninvasive prenatal screens
  • NIPS
  • trisomy 21

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