EP18.04: Postpartum placental cytogenetic analyses from pregnancies with discordant cell‐free DNA screening results

We aimed to conduct cytogenetic analyses of placentas collected at birth from women who received high-risk cell-free DNA (cfDNA) screening results which were discordant with fetal chromosome diagnostic investigations, to assess what proportion of ‘false-positive’ screening results are attributable to confined placental mosaicism (CPM). This ongoing research is a cohort study involving maternity patients at participating practices in Melbourne, Australia, who are identified as having had a high-risk cfDNA screening result which was discordant with euploid fetal diagnostic investigations. After birth, placentas from these women are biopsied in each quadrant, with samples being combined and then processed using direct microarray analysis. Placentas are also collected from a control cohort of women with low-risk cfDNA results, with a 2:1 ratio of controls to cases. Samples are analysed to a depth of 4Mb on the chromosome flagged by cfDNA screening, in order to identify CPM as a cause of the screening result. This study remains ongoing. Thus far, we have obtained cytogenetic results from 30 women with ‘false-positive’ cfDNA results. Of these placentas, 11/30 (36.7%) were confirmed to contain CPM, with the remaining 19 (63.3%) being euploid. Placentas affected by CPM included cfDNA results for various trisomies, sex chromosome aneuploidies and segmental copy number variants, with no discernible association between chromosome anomaly type and prevalence of CPM. All 30 control placentas analysed thus far have been euploid. CPM is a significant contributor to false-positive cfDNA results, but does explain all cases of ‘false-positive’ cfDNA results. Along with trisomy, segmental copy number variant results may also arise from CPM, thereby the use of chorionic villus sampling as opposed to amniocentesis should be carefully considered for women with these results so as to not give false indication of fetal chromosome anomalies.