Evaluation of noninvasive prenatal screening for copy number variations among screening laboratories.

OBJECTIVE: To evaluate the current situation of expanded noninvasive prenatal screening (NIPS) for copy number variations (CNVs) in laboratories in China, the National Center of Clinical Laboratories conducted an externalqualityassessment (EQA) program.

METHODS: The EQA panel consisted of 12 artificial samples associated with different syndromes, which were mixed with maternal plasma collected from pregnant women and enzyme-digested cell-free DNA (cfDNA) from cell lines with different fetal fractions (FFs) ranging from 5% to 15%. The panel was validated by next-generation sequencing and distributed to laboratories, along with questionnaires and case scenarios.

RESULTS: Sixty-nine laboratories participated in the EQA program, and 91.30% (63/69) of laboratories correctly identified all samples. A total of 7.25% (5/69) of the laboratories reported false-negative results, and 2.90% (2/69) of the laboratories reported unexpected CNVs. The correct rates of the 22q11.2 deletion syndrome, Cri-du-chat syndrome, 1p36 deletion syndrome and Angelman/Prader-Willi syndrome samples were 97.46%, 98.55%, 100%, and 100%, respectively. With the increase in the FF, deletion size, and read depth, the detection rate increased. For results reports, only five laboratories reported FF values, one laboratory reported the CNV classification type, and none reported sensitivity, specificity, positive predictive values, and negative predictive values.

CONCLUSION: The detection capabilities of NIPS for CNVs still need to be improved and standardized, and FF, deletion size, and read depth are factors that affect the detection rate.