Prenatal Cell-Free DNA Screening With Fetal Enrichment Enables Sampling From 8 Weeks of Gestational Age.

Abstract

Cell-free DNA (cfDNA) screening for fetal aneuploidy is typically offered from 10 weeks of gestational age (GA) onward. Fetal fraction (FF) enrichment may enable screening before 10 weeks with a low failure rate. This study aimed to assess the feasibility of cfDNA screening with in vitro enrichment before 10 weeks of gestation. 435 pregnant women were recruited between 7w0d and 9w6d of GA (EARLY samples) and scheduled for a second cfDNA sample after 11 weeks of GA (12w+ samples). 371 women provided both an EARLY and a 12w+ sample, and we compared cfDNA results between EARLY and 12w+ samples and sex at birth. For sex determination using cfDNA, EARLY, and 12w+ samples were 100% concordant with clinical sex at birth. In 170 male pregnancies, EARLY samples 5.9% had FF < 4% after enrichment. Seven aneuploidies were observed early, but eight at 12+ weeks (one false positive after invasive diagnostic testing). We observed 4.4% spontaneous abortions between the EARLY and 12w+ sampling. Our findings suggest that in vitro fetal enrichment provides sufficient cfDNA for reliable prenatal cfDNA screening results as early as 8 weeks, but one limitation lies in the high proportion of spontaneous abortions before 12w0d.