Simulated confined placental mosaicism proportion (SCPMP) based on cell‐free fetal DNA fraction enrichment can reduce false‐positive results in non‐invasive prenatal testing

Abstract Objective To decrease the false‐positive rate of NIPT using cell‐free fetal DNA (cffDNA) fraction enrichment and the simulated confined placental mosaicism proportion (SCPMP) threshold application via cffDNA quantification. Method Using a cffDNA enrichment method, 303 plasma samples with positive NIPT results ( Z ‐score > 3.0; 200 true‐positive and 103 false‐positive cases) were re‐sequenced. A method to calculate the SCPMP based on the quantified cffDNA fraction was developed; the SCPMP threshold between true‐ and false‐positive NIPT results was determined and used for re‐analyses. Results With enrichment, the fetal fraction of the 303 samples was 26.9 ± 8.4%, compared to 11.0 ± 3.2% without enrichment. The optimized threshold method with double determination using the Z‐value‐defined SCPMP can reduce the false‐positive rates for trisomies 21, 18, and 13 by 87%, 80%, and 88.9%, respectively. Conclusion Our optimized method can decrease the false‐positive rate of NIPT results.