Clinical Implications and Limitations of Noninvasive Prenatal Testing for Detecting Fetal Copy Number Variations: A...

BACKGROUND This study evaluated the real-world diagnostic performance and limitations of noninvasive prenatal testing (NIPT) in detecting fetal copy number variations (CNVs) within a large multicenter cohort in Shaanxi Province. MATERIAL AND METHODS This retrospective observational study analyzed 18 525 cases of NIPT at the First Affiliated Hospital of Xi'an Jiaotong University, a referral center for NIPT, from June 2023 to November 2024. Karyotype analysis and CNV sequencing were conducted on the fetuses and/or parents, with follow-up on pregnancy outcomes. RESULTS Abnormal CNVs were detected in 218 cases (1.18%; 218/18525), of which 129 women (59.17%; 129/218) opted for invasive diagnostic confirmation from 38 hospitals in 7 prefectural-level cities. The positive predictive value (PPV) for aberrant CNVs following NIPT was only 48.06% (62/129; 95% CI, 39.4-56.7%), with 28.57% (18/62) possessing pathogenic CNVs. We noted that PPV estimates were based on self-selected confirmatory testing, which might inflate or deflate performance estimates. The detection efficiency varied significantly by chromosomal location; chromosome 18 showed the highest PPV at 83.33% (15/18; P<0.05), notably within the 18p11.23-p11.31 segment. Furthermore, smaller CNVs (<5 Mb) demonstrated a higher concordance rate (PPV 54.74%; 52/95) than larger fragments (>10 Mb). Regional analysis indicated Hanzhong and Xi'an demonstrated elevated PPVs, while Yulin showed the highest incidence of pathogenic CNVs. CONCLUSIONS NIPT demonstrates moderate performance for fetal CNV detection, with a PPV of approximately 48%. Its clinical utility is maximized when combined with ultrasound findings, which significantly increase the predictive value. The stakeholders should be aware of this limitation when interpreting results.