Enhanced Detection of Genetic Abnormalities in High-Risk Pregnancies Using CNV-Seq Compared to Karyotyping

Genetic abnormalities in high-risk pregnancies present substantial threats to both maternal and fetal well-being, frequently resulting in poor outcomes and imposing significant burdens on healthcare resources. This study aimed to evaluate the efficacy of copy number variation sequencing (CNV-seq) compared to karyotyping in identifying genetic abnormalities among high-risk pregnant women. A cohort of 3,335 high-risk pregnancies (median maternal age: 32.5 years, median gestational age: 24.5 weeks) was analyzed, with indications including advanced maternal age, abnormal screening results, and prior adverse outcomes. Karyotyping detected abnormalities in 7.7% (256/3,335) of cases, while CNV-seq identified 14.6% (487/3,335), demonstrating superior sensitivity, particularly for structural variations (50 pathogenic CNVs vs. 13 by karyotyping). Follow-up data (97.7% coverage) revealed that 7% of pregnancies were terminated due to genetic abnormalities, primarily trisomies 21, 18, and 13, with low rates of neonatal death (0.3%) and subsequent miscarriage (0.5%). Additionally, parental verification of 30 cases with uncertain pathogenicity showed 12 suspected pathogenic CNVs, most resulting in normal outcomes upon continued pregnancy. Despite limitations such as lack of wet lab validation and potential batch effects, this study highlights CNV-seq as a transformative tool for prenatal diagnosis, offering higher detection rates and enabling informed clinical decision-making. Future research should focus on integrating CNV-seq into routine screening protocols, optimizing cost-effectiveness, and enhancing genetic counseling frameworks to further improve pregnancy outcomes.