Skip to content
DraconiticResearch
Search Sources API
203,948 studies31 sourcesUpdated 45 min ago
Peer-reviewedCC BY 4.0Frontiers in Endocrinology

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

  • Haimei Qi1
  • Haijun Chen2
  • Xianping Yuan3
  • Jinhui Gan2
  • Huifeng Liu1
  • Xinxing Xie2
  • Qing Xie2
  • Junkun Chen2
  • Shichun Shen2
  • Liyun Song4
4 affiliations
  1. 1Department of Clinical Laboratory, Ganzhou Women and Children’s Health Care Hospital
  2. 2Department of Medical Genetics, Ganzhou Women and Children’s Health Care Hospital
  3. 3Department of Obstetrics, Ganzhou Women and Children’s Health Care Hospital
  4. 4Department of Clinical Laboratory, Ganzhou People’s Hospital
Read full textPDFDOICite

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.

Related

  1. The limits of genetic screening: trisomy 21 after euploid preimplantation genetic testing for aneuploidy and negative noninvasive prenatal testing.
    Jennifer Law, Kyra Ramsey, Nicole Sprawka +1
    F&S reportsPeer-reviewedCC BYFull textObstetrics, gynaecology & paediatricsEurope PMC
  2. Chromosomal and genetic causes of primary ovarian insufficiency in the Utah population
    Journal of the Endocrine SocietyPeer-reviewedCC BY-NC-NDFull textEndocrinology & metabolismEurope PMC
  3. Clinical utility of prenatal exome sequencing after normal chromosomal microarray in fetuses with structural anomalies
    M. Perriere, W. Darwiche, K. Messaoudi +8
    MorphologiePeer-reviewedCC BY-NC-NDFull textGenetics & genomicsHuman geneticsHAL
  4. Noninvasive ventilation in patients with amyotrophic lateral sclerosis: Is home sleep apnea testing a useful tool for initiating noninvasive ventilation?
    Chiara Sanna, Mauro Sanna, Giuseppe Borghero +1
    Multidisciplinary Respiratory MedicinePeer-reviewedCC BY-NC 4.0Full textPhysiologyPMC
  5. Results from the VANISH study: A prospective multicenter study validating a single-nucleotide polymorphism-based noninvasive prenatal test to assess aneuploidy risk in surviving twins of vanishing twin pregnancies.
    Lorraine Dugoff, Sunni L Mumford, Meredith L Rochon +27
    Pregnancy (Hoboken, N.J.)Peer-reviewedCC BY-NC-NDFull textObstetrics, gynaecology & paediatricsEurope PMC

Cite

BibTeXRIS
BibTeX
@article{qi2026causes,
  title = {{Causes of discordance between noninvasive prenatal testing and fetal chromosomal status: a 10-year cohort study of 97, 743 cases}},
  author = {Haimei Qi and Haijun Chen and Xianping Yuan and Jinhui Gan and Huifeng Liu and Xinxing Xie and Qing Xie and Junkun Chen and Shichun Shen and Liyun Song},
  journal = {Frontiers in Endocrinology},
  year = {2026},
  month = oct,
  doi = {10.3389/fendo.2026.1945762},
  url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1945762/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Causes of discordance between noninvasive prenatal testing and fetal chromosomal status: a 10-year cohort study of 97, 743 cases
AU  - Haimei Qi
AU  - Haijun Chen
AU  - Xianping Yuan
AU  - Jinhui Gan
AU  - Huifeng Liu
AU  - Xinxing Xie
AU  - Qing Xie
AU  - Junkun Chen
AU  - Shichun Shen
AU  - Liyun Song
PY  - 2026
DA  - 2026/10/20
JO  - Frontiers in Endocrinology
DO  - 10.3389/fendo.2026.1945762
UR  - https://www.frontiersin.org/articles/10.3389/fendo.2026.1945762/full
AB  - 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.
SN  - 1664-2392
ER  -