Variability of “Reported Fetal Fraction” in Noninvasive Prenatal Screening (NIPS)

Abstract

Abstract Background Fetal fraction is often used to designate no-calls in noninvasive prenatal screening (NIPS). We wished to compare the variability in determining fetal fraction to gold standard methods. Methods We identified 6 publications with datasets consisting of methods capable of measuring fetal fraction for all samples that also had comparison data from gold standard methods. Examples of gold standard methods included relative Y-chromosome quantification in cases of male fetus pregnancies or relative quantification of the relevant chromosome for pregnancies affected by one of the 3 major trisomies. Results The studies showed that the differences of the various fetal fraction measurement assays as compared to a gold standard measurement displayed a standard deviation (SD) in the range of 1.3–3.4% fetal fraction (FF). The 4 studies that measured FF from fragment size and genomic coordinates or single nucleotide polymorphisms had a lower variability, with a median SD of about 1.6%, whereas 2 other studies using different methods displayed significantly higher variability. Conclusion When deciding whether to use the reported FF as a reason to discard samples as no-calls or not, we recommend taking the variability of the FF measurement into consideration.