OBJECTIVES: 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.
OBJECTIVES: 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: Athena M Cherry; Yassmine M Akkari; Kimberly M Barr; Hutton M Kearney; Nancy C Rose; Sarah T South; James H Tepperberg; Jeanne M Meck Journal: Genet Med Date: 2017-07-20 Impact factor: 8.822
Authors: Malgorzata Ilona Srebniak; Maarten F C M Knapen; Marieke Joosten; Karin E M Diderich; Sander Galjaard; Diane Van Opstal Journal: Mol Cytogenet Date: 2021-01-09 Impact factor: 2.009
Authors: Dick Oepkes; G C Lieve Page-Christiaens; Caroline J Bax; Mireille N Bekker; Catia M Bilardo; Elles M J Boon; G Heleen Schuring-Blom; Audrey B C Coumans; Brigitte H Faas; Robert-Jan H Galjaard; Attie T Go; Lidewij Henneman; Merryn V E Macville; Eva Pajkrt; Ron F Suijkerbuijk; Karin Huijsdens-van Amsterdam; Diane Van Opstal; E J Joanne Verweij; Marjan M Weiss; Erik A Sistermans Journal: Prenat Diagn Date: 2016-11-15 Impact factor: 3.050