Impact of mosaicism ratio on positive predictive value of cfDNA screening. (25th November 2020)

• Record Type: Journal Article
• Authors: Rafalko, Jill M.; Caldwell, Samantha; Tynan, John; Almasri, Eyad; Weinblatt, Vivian; McCullough, Ron
• Is Part Of: Prenatal diagnosis. Volume 41:Number 1(2021)
• Page Start: 28
• Page End: 34
• Publication Date: 2020-11-25
• Subjects: Prenatal diagnosis -- Periodicals; Fetus -- Diseases -- Diagnosis -- Periodicals; Electronic journals; 618.32075
• DOI: 10.1002/pd.5863
• Languages: English
• ISSNs: 0197-3851

Abstract

Abstract: Objective: To examine the relationship between the fraction of cell‐free DNA (cfDNA) affected by aneuploidy compared to the overall fetal fraction of a prenatal screening specimen and its effect on positive predictive value (PPV). Method: CfDNA specimens positive for trisomy 13, 18, and 21 with diagnostic outcomes were analysed over a 22‐month period in one clinical laboratory. For each positive specimen, a "mosaicism ratio" (MR) was calculated by dividing the fraction of cfDNA affected by aneuploidy by the overall fetal fraction of the specimen. PPVs were calculated and analyzed based on various MR ranges. Results: Trisomy 13 was the aneuploidy most commonly seen in mosaic form, followed by trisomy 18 and trisomy 21. Significant differences in positive predictive values were noted for all three trisomies between samples with an MR in the "mosaic" versus "non‐mosaic" range, as well as between results classified as "low‐mosaic" versus "high‐mosaic." Conclusion: PPVs may be influenced, in part, by the mosaicism ratio associated with a particular result. The data generated from this study may be useful in providing more personalized risk assessments for patients with positive cfDNA screening results.