In the era of copy number variation sequencing: changes in the target population for prenatal diagnosis and what is the optimal prenatal diagnostic strategy?

Purpose: Copy number variation sequencing (CNV-Seq) has become a first-line prenatal diagnostic technology. The purpose of this study was to investigate the changes in the target population for prenatal diagnosis in the CNV-Seq era and to assess the clinical value and economic costs of combining the use of CNV-Seq with karyotyping. Methods: The prenatal diagnostic indications of 3,931 pregnant women (3,952 samples of amniotic fluid) in three groups were statistically analyzed. The detection rates (DRs) of karyotype or CNV-Seq for each indication were determined. The abnormal results from karyotyping or CNV-Seq were analyzed. The detection efficiencies of karyotyping and CNV-Seq for each type of chromosomal abnormality were compared. The DRs of chromosomal abnormalities and the economic costs of the three prenatal diagnosis strategies were assessed. Results: Ultrasonic anomalies were the leading indications for the occurrence of copy number variation in prenatal diagnosis. The DRs for chromosomal abnormalities were 3.72% with karyotyping and 16.20% with CNV-Seq. The DRs of chromosomal abnormalities increased from 7.02% to 15.81% when CNV-Seq was combined with karyotyping in the Karyotype and CNV-Seq group. CNV-Seq confirmed the small supernumerary marker chromosome and unidentified karyotypes detected by karyotyping. Both karyotyping and CNV-Seq are capable of detecting low-level mosaicism. Conclusion: In the era of CNV-Seq, the target population for prenatal diagnosis is expanding. Combining CNV-Seq with karyotyping can increase the DRs of fetal chromosomal abnormalities. Therefore, combined testing is an efficient and relatively cost-effective prenatal diagnostic strategy.