The Application Value of Chromosome Microarray Analysis in Prenatal Diagnosis of Clinically Relevant Copy Number Variations in Fetuses

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Objective: Exploring the clinical application value of chromosome microarray analysis (CMA) technology in detecting clinically relevant copy number variations (CNVs) in fetuses and evaluating its efficacy in prenatal diagnosis. Methods: A retrospective analysis was conducted on 2860 pregnant women undergoing prenatal diagnosis between January 2019 and August 2023. All cases received concurrent G-banded karyotyping and CMA. Detection rates were compared and stratified by clinical indications (eg, structural anomalies, increased nuchal translucency NT). CNVs were classified per ACMG guidelines. Parental origin verification and neonatal follow-up (6 months to 2 years) were performed to correlate CNVs with postnatal phenotypes. Results: CMA yielded a significantly higher overall detection rate than karyotyping (14.41% vs 10.10%, P<0.05), identifying 238 pathogenic (8.32%), 62 likely pathogenic (2.17%), and 112 VUS (3.92%) cases. The highest CMA yield occurred in fetuses with structural anomalies (26.85%), particularly multi-system defects (25.16% P/LP yield). Pathogenic yields also rose progressively with NT thickness. Of the 300 P/LP CNVs, 54.00% were microdeletions and 61.33% were <5 Mb, with DiGeorge syndrome being most prevalent (5.67%). De novo P/LP CNVs showed a significantly higher rate of abnormal postnatal phenotypes (40.00%) compared to inherited cases (10.53%, P<0.05). For VUS, inherited cases had a significantly higher postnatal normality rate (93.75%) than de novo variants (66.67%, P<0.05). Conclusion: Based on large sample data, this study confirms that CMA technology can not only improve the overall detection rate of fetal chromosomal abnormalities, but also effectively identify submicroscopic CNVs within the blind spots of traditional karyotype analysis. It serves as a high-value first-line tool for fetuses with multisystem anomalies or increased NT. Parental origin verification is critical for refining VUS interpretation and guiding pregnancy management.

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