ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1645223
Performance and Clinical Implications of Non-Invasive Prenatal Testing for Rare Chromosomal Abnormalities: A Retrospective Study of 94,125 Cases
Provisionally accepted
Haimei Qi1Haijun Chen2Zhuling Zhang3Jinhui Gan2Huifeng Liu1Xianping Yuan3Fuyu Luo2
Junkun Chen2
Shichun Shen2*- 1Clinical Laboratory, Ganzhou Maternal and Child Health Care Hospital, Ganzhou, China
- 2Department of Medical Genetics, Ganzhou Maternal and Child Health Care Hospital, Ganzhou, China
- 3Obstetrical Department, Ganzhou Maternal and Child Health Care Hospital, Ganzhou, China
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Background: Non-invasive prenatal testing (NIPT) has demonstrated robust performance in detecting common trisomies and copy number variations. However, its clinical utility for rare chromosomal abnormalities (RCAs) remains controversial due to low positive predictive value (PPV).This study retrospectively analyzed the data of 94,125 cases that underwent NIPT at Ganzhou Maternal and Child Health Hospital in China. This dataset was used to evaluate NIPT performance in RCAs detection and track pregnancy outcomes of positive cases.In the cohort of 94,125 pregnancies undergoing NIPT, 336 cases (0.36%) were found to carry RCAs. Among them, 102 cases underwent validation through karyotyping and/or chromosome microarray analysis. Of the 102 validated cases, 7 were true positives (PPV=6.86%). Additionally, 3 cases exhibited uniparental disomy consistent with the NIPT-reported chromosomal anomalies. Of 268 singleton neonates, 68 (25.37%) were small-for-gestational-age.Conclusions: This study found that most NIPT-detected RCAs were associated with maternal age, while Trisomy 7 occurred independently of maternal age. Concurrent use of karyotyping and chromosome microarray analysis, rather than karyotyping alone, mitigates culture-related bias and enhances the PPV. Both biological and methodological factors contribute to the low PPV of NIPT for RCAs. Despite a low PPV, pregnancies with NIPT-indicated RCAs showed elevated risks of fetal loss, small-for-gestational-age, and uniparental disomy, though not preterm birth. Thus, NIPTdetected RCAs retain clinical significance for risk stratification and pregnancy management.
Keywords: Noninvasive prenatal testing, rare chromosomal abnormalities, Positive predictive value, true fetal mosaicism, pregnancy outcomes, Small-for-gestational-age
Received: 11 Jun 2025; Accepted: 07 Aug 2025.
Copyright: © 2025 Qi, Chen, Zhang, Gan, Liu, Yuan, Luo, Chen and Shen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shichun Shen, Department of Medical Genetics, Ganzhou Maternal and Child Health Care Hospital, Ganzhou, China
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