Enrichment of Fetal Cell-Free DNA in Early Miscarriages for Detection of Aneuploidy: A Novel Approach

Early pregnancy losses are commonly linked to chromosomal abnormalities, but such a diagnosis can be difficult to achieve due to the unavailability of the product of conception and the low fetal fraction in maternal blood, which makes cell-free DNA (cfDNA) analysis difficult. Using in vitro enrichment by stringent cfDNA fragment size selection before analysis among 24 women with early pregnancy losses, we show a strong increase of fetal fraction (P < 0.001), enabling aneuploidy screening in all of them. We also observed an increased rate of aneuploidy with gestational age at loss (from 13% to 88%, P = 0.01). Using a highly efficient in vitro enrichment of fetal cfDNA may allow genetic screening in early pregnancy losses.