Performance of Prenatal Cell‐Free DNA Screening for Foetal Chromosome Aneuploidies and Microdeletion/Microduplication Syndromes: A Retrospective Study of 64,482 Consecutive Cases From a Prenatal Diagnosis Centre in China

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OBJECTIVE: Prenatal cell-free DNA (cfDNA) screening has shown high accuracy for common trisomies, but its application in screening for sex chromosome aneuploidies (SCAs), rare autosomal aneuploidies (RAAs) or microdeletion/microduplication syndromes (MMSs) requires more supportive data. METHODS: Between 2017 and 2023, a total of 67,742 pregnant women were screened for foetal aneuploidies using cfDNA-based next-generation sequencing (NGS). Pregnant women with high-risk results were recommended to undergo invasive prenatal diagnosis to confirm the findings and were explicitly offered the choice to accept or decline the procedure. RESULTS: A total of 1148 high-risk results with foetal chromosome aneuploidies and/or copy number variations (CNVs) were identified from prenatal cfDNA screening. These cases included 432 common aneuploidies, 374 SCAs, 77 RAAs, and 265 CNVs. The positive predictive values (PPVs) were 82.6% (95% CI: 77.3%-86.9%) for T21, 56.3% (95% CI: 45.6%-66.7%) for T18%, and 33.9% (95% CI: 24.1%-47.3%) for T13. The overall PPVs were 45.5% (95% CI:38.9%-52.3%) for SCAs, 60.8% (95% CI: 51.6%-69.5%) for CNVs, and 57.8% (95% CI: 43.3%-71.4%) for known MMSs. Among the SCAs, the highest PPV was observed for 47,XXY (76.6%, 95% CI: 60.6%-84.8%), followed by 47,XXX (58.1%, 95% CI: 39.3%-72.9%), 45,X (33.1%, 95% CI: 26.1%-41.9%), and 47,XYY (30.8%, 95% CI: 15.5%-61.6%). Among the CNVs, 70.97% were determined to be pathogenic or likely pathogenic. Additionally, one false-negative result for T21 and three cases of maternal malignancies were detected in our study population. CONCLUSION: This study emphasises the significant clinical utility of prenatal cfDNA screening in assessing the risk of foetal chromosomal abnormalities; however, its applicability remains limited for RAA screening. Comprehensive long-term phenotype follow-up is essential to elucidate the clinical significance of CNVs.

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