The type of feto‐placental aneuploidy detected by cfDNA testing may influence the choice of confirmatory diagnostic procedure

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. © 2015 John Wiley & Sons, Ltd.