OBJECTIVES: This study aims to assess the value of copy number variation sequencing (CNV-seq) in prenatal diagnosis of abnormal ultrasound markers to reduce fetal birth defects. METHODS: Between June 2021 and December 2022, Yulin Maternal and Child Health Care Hospital examined 295 pregnant women with abnormal ultrasound indicators. We were categorized by the number of abnormalities and age. Karyotype analysis and CNV-seq were conducted, and the CNV-seq detection rate was statistically analyzed. RESULTS: CNV-seq detected abnormal chromosomes in 43 out of 295 pregnant women with abnormal fetal ultrasound soft indicators, resulting in a detection rate of 14.58 %, compared to 5.76 % with traditional karyotype analysis. CNV-seq identified all aneuploidy abnormalities found by karyotype analysis and an additional 5 abnormalities, increasing the detection rate by 1.69 %. However, CNV-seq missed one case of chromosome equilibrium translocation. The detection rate of CNV-seq in fetuses with Several abnormal soft indexes was 29.41 %, significantly higher than individual soft indexes (p<
0.05). The study compared abnormality rates of single and multiple ultrasound soft markers in two age groups. Abnormal detection rates were 12.38 % for the younger group and 13.73 % for the older group, with no significant difference. However, the younger group had a significantly higher detection rate for multiple soft markers compared to the older group (χ CONCLUSIONS: CNV-seq technology is valuable for identifying fetuses with abnormal soft markers, guiding its future use in perinatal diagnosis and aiding clinical genetic counseling.