Performance and clinical implications of non-invasive prenatal testing for rare chromosomal abnormalities: a retrospective study of 94,125 cases.

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Frontiers in Molecular Biosciences Pub Date : 2025-08-20 eCollection Date: 2025-01-01 DOI:10.3389/fmolb.2025.1645223

Haimei Qi, Haijun Chen, Zhuling Zhang, Jinhui Gan, Huifeng Liu, Xianping Yuan, Fuyu Luo, Junkun Chen, Shichun Shen

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引用次数: 0

Abstract

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).

Methods: 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.

Results: 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, seven 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.

Conclusion: This study found that most NIPT-detected RCAs were associated with maternal age, while Trisomy seven 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, NIPT-detected RCAs retain clinical significance for risk stratification and pregnancy management.

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罕见染色体异常的无创产前检测的表现和临床意义：94125例回顾性研究。

背景：无创产前检测（NIPT）在检测常见三体和拷贝数变异方面表现出强大的性能。然而，由于阳性预测值较低，其在罕见染色体异常（RCAs）中的临床应用仍存在争议。方法：回顾性分析赣州妇幼保健院94125例NIPT患者的资料。该数据集用于评估NIPT在RCAs检测中的表现，并跟踪阳性病例的妊娠结局。结果：在接受NIPT的94125例妊娠队列中，发现336例（0.36%）携带RCAs。其中102例通过核型和/或染色体微阵列分析进行验证。102例确诊病例中，真阳性7例（PPV = 6.86%）。此外，3例表现出与npt报告的染色体异常一致的单亲二体。268例单胎新生儿中，68例（25.37%）胎龄小。结论：本研究发现，大多数npt检测到的RCAs与母亲年龄有关，而七号三体的发生与母亲年龄无关。同时使用核型和染色体微阵列分析，而不是单独使用核型分析，可以减轻与培养相关的偏见，提高PPV。生物学和方法学因素都是导致rca NIPT低PPV的原因。尽管PPV较低，但npt指示的RCAs妊娠显示胎儿丢失、胎龄小和单亲畸形的风险升高，但没有早产。因此，npt检测的RCAs在风险分层和妊娠管理方面具有临床意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

期刊介绍： Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.