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.