Work

Causes of discordance between noninvasive prenatal testing and fetal chromosomal status: a 10-year cohort study of 97, 743 cases

Year: 2026

Type: article

Abstract: Background: Noninvasive prenatal testing (NIPT) has been widely adopted for screening common fetal chromosomal aneuploidies, yet discordance between NIPT results and true fetal karyotypes remains a critical challenge limiting its clinical utility. Methods: We retrospectively analyzed 97, 743 pregnant women who underwent NIPT at Ganzhou Women and Children's Health Care Hospital between April 2015 and December 2024 to evaluate the performance of NIPT and investigate the causes of discordance between NIPT results and fetal outcomes. Results: A total of 481 NIPT-positive cases were identified, yielding an overall positive rate of 0.49%. Of these, 380 cases underwent confirmatory testing (377 via invasive prenatal diagnosis and 3 via postnatal karyotyping). The overall positive predictive value (PPV) for the three common trisomies was 71.84%, with T21 showing the highest PPV (84.38%), followed by T18 (56.00%) and T13 (4.76%). Stratified analysis by Z-score demonstrated that PPVs for both T21 and T18 increased progressively with higher Z-score. For T21, PPV rose from 21.95% (Z: 3-6) to 100% (Z > 20); a similar upward trend was observed for T18. False-positive results were attributed to multiple mechanisms, including maternal chromosomal abnormalities (4 full 47, XX, + 21, 1 mosaic), vanishing twin (7 cases), uniparental disomy (2 cases), and confined placental mosaicism (CPM) (2 cases). Only 3 false-negative cases were identified, predominantly due to low-level placental mosaicism. Conclusions: Discordance between NIPT and fetal karyotype exhibits a clear directional divergence: false-positive results are etiologically heterogeneous, involving maternal chromosomal abnormalities, substantially underestimated vanishing twin, CPM, and technical factors, whereas false-negative results are predominantly attributable to low-level CPM. Systematic analysis of Z-scores, maternal characteristics, and follow-up data can effectively identify most discordance causes, providing precise evidence for genetic counseling and pregnancy management. Our analytical framework provides a practical reference for optimizing NIPT screening strategies and reducing unnecessary invasive procedures in other regions.

Source: Frontiers in Endocrinology

DOI: 10.3389/fendo.2026.1945762