Non-invasive prenatal screening for foetal trisomy: An assessment of reliability and reporting

Objective Non-invasive prenatal screening (NIPS) has been introduced as a routine screening technique for aneuploidies in the clinic. To evaluate its reliability and reporting standardization, the National Center for Clinical Laboratories launched an external quality assessment (EQA) program based on highly simulated samples. Methods Maternal and child paired cell lines were digested by enzymes to obtain DNA fragments for the analysis panel, which were composed of 5% T21, 5% T18, 10% T13, 10% euploid, and 20% T18 samples. The samples were validated and distributed to laboratories along with scenarios and questionnaires for analysis. Results Out of 350 participating laboratories, 98.6% correctly identified all samples. The concurrence rates of laboratories for the 5% T21, 5% T18, 10% T13, 10% euploid, and 20% T18 samples were 98.9%, 99.7%, 99.7%, 100%, and 100%, respectively. Enrichment increased the foetal fraction (FF) values by 2∼3-fold, but the z scores generated by the enrichment group fluctuated greatly. Other FF estimation techniques, such as the size-based and FF-QuantSC methods, generated slightly different FF values from the chr Y-based method. Furthermore, some laboratories omitted the suggestions of results in reports. Conclusions The participating laboratories provided highly reliable results for samples with relatively higher FF values. However, the absence of performance validation, laboratory errors, and low FF values were potential reasons for false-negative results. In addition, enrichment operations should be validated and normalized to guarantee NIPS reproducibility, plus further efforts are required to standardize the NIPS reports.