Noninvasive Prenatal Testing Prone to Fetal Fraction Variability

For a paper in Clinical Chemistry, a team at the University Medical Center Utrecht, Vrije Universiteit Amsterdam, and other centers tracks the proportion of cell-free fetal DNA found in maternal blood samples during noninvasive prenatal testing (NIPT). The investigators saw a range of fetal fraction estimates and fetal fraction reporting frequencies by NIPT labs when they looked at fetal fractions in 477 fetal aneuploidy screening samples that had been collected around the world; tested by a range of NIPT providers using sequencing, array, or digital PCR approaches; and evaluated by the European Molecular Genetics Quality Network and Genomic Quality Assessment in 2018, 2019, and 2020. From there, the authors consider fetal fractions found in a single sample tested for trisomy 21 with multiple whole-genome sequencing-based analyses, along with fetal fraction estimates established with Veriseq2 and SeqFF bioinformatic tools for almost 87,400 more NIPT samples from an NIPT in Amsterdam. Based on their results, the authors suggest that fetal fraction estimates "should be regarded as a laboratory-specific range, rather than a precise number," whereas "strict universal minimum thresholds might result in unnecessary test failures and should be used with caution."