title: The type of feto-placental aneuploidy detected by cfDNA testing may influence the choice of confirmatory diagnostic procedure.
abstract: OBJECTIVE
  Cell-free DNA (cfDNA) screening can provide false positive/negative results because the fetal fraction originates primarily from trophoblast. Consequently, invasive diagnostic testing is recommended to confirm a high-risk result. Currently, there is debate about the most appropriate invasive method. We sought to estimate the frequency in which a chorionic villus sampling (CVS) performed after a high-risk cfDNA result would require a follow-up amniocentesis due to placental mosaicism.
  
  
  METHODS
  Analyses of the frequencies of the different types of mosaicism involving cytotrophoblasts, for trisomies 21 (T21), 18 (T18), 13 (T13) and monosomy X (MX) among 52,673 CVS karyotypes obtained from cytotrophoblast, mesenchyme and confirmatory amniocentesis.
  
  
  RESULTS
  After a high-risk cfDNA result for T21, 18, 13 and MX, the likelihood of finding CVS mosaicism and need for amniocentesis is, respectively, 2%, 4%, 22% and 59%. When mosaicism is detected by CVS, the likelihood of fetal confirmation by amniocentesis is, respectively, 44%, 14%, 4% and 26%.
  
  
  CONCLUSIONS
  In cases of high-risk cfDNA results for T21/T18, CVS (combining cytotrophoblast and mesenchyme analysis) can be considered, but with the caveat of 2-4% risk of an inconclusive result requiring further testing. In high-risk results for MX/T13, amniocentesis would appear to be the most appropriate follow-up diagnostic test, especially in the absence of sonographic findings.
authors.affiliation: Toma Advanced Biomedical Assays, Busto Arsizio, Varese, Italy.
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Grati
authors.affiliation: Department of Obstetrics, Gynecology and Women's Health at Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Komal
authors.initials: K
authors.lastname: Bajaj
authors.affiliation: Toma Advanced Biomedical Assays, Busto Arsizio, Varese, Italy.
authors.forename: Francesca
authors.identifier: http://orcid.org/0000-0002-8673-2944
authors.initials: F
authors.lastname: Malvestiti
authors.affiliation: Toma Advanced Biomedical Assays, Busto Arsizio, Varese, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Agrati
authors.affiliation: Toma Advanced Biomedical Assays, Busto Arsizio, Varese, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Grimi
authors.affiliation: Toma Advanced Biomedical Assays, Busto Arsizio, Varese, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Malvestiti
authors.affiliation: Toma Advanced Biomedical Assays, Busto Arsizio, Varese, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Pompilii
authors.affiliation: Toma Advanced Biomedical Assays, Busto Arsizio, Varese, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Maggi
authors.affiliation: Department of Obstetrics, Gynecology and Women's Health at Albert Einstein College of Medicine, Bronx, NY, USA.|Natera, San Carlos, CA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Gross
authors.affiliation: Toma Advanced Biomedical Assays, Busto Arsizio, Varese, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Simoni
authors.affiliation: Department of Obstetrics, Gynecology and Women's Health at Albert Einstein College of Medicine, Bronx, NY, USA.|1st Department of Obstetrics and Gynecology, Medical University of Warsaw, 02-015, Warsaw, Poland.
authors.forename: Jose Carlos P
authors.initials: JC
authors.lastname: Ferreira
mesh_terms: D005189:False Positive Reactions; D005260:Female; D006801:Humans; D062145:Maternal Serum Screening Tests; D009030:Mosaicism; D011247:Pregnancy; D012189:Retrospective Studies; D014314:Trisomy