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

ABSTRACT 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.