Qi Haimei, Chen Haijun, Zhang Zhuling, Gan Jinhui, Liu Huifeng, Yuan Xianping, Luo Fuyu, Chen Junkun, Shen Shichun
Clinical Laboratory, Ganzhou Maternal and Child Health Hospital, Ganzhou, China.
Department of Medical Genetics, Ganzhou Maternal and Child Health Hospital, Ganzhou, China.
Front Mol Biosci. 2025 Aug 20;12:1645223. doi: 10.3389/fmolb.2025.1645223. eCollection 2025.
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, 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.
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.
无创产前检测（NIPT）在检测常见三体和拷贝数变异方面已显示出强大的性能。然而，由于阳性预测值（PPV）较低，其在检测罕见染色体异常（RCA）方面的临床效用仍存在争议。
本研究回顾性分析了在中国赣州市妇幼保健院接受NIPT的94125例病例的数据。该数据集用于评估NIPT在RCA检测中的性能，并追踪阳性病例的妊娠结局。
在接受NIPT的94125例妊娠队列中，发现336例（0.36%）携带RCA。其中，102例通过核型分析和/或染色体微阵列分析进行了验证。在102例经验证的病例中，7例为真阳性（PPV = 6.86%）。此外，3例表现出与NIPT报告的染色体异常一致的单亲二体。在268例单胎新生儿中，68例（25.37%）为小于胎龄儿。
本研究发现，大多数NIPT检测到的RCA与母亲年龄有关，而7号三体的发生与母亲年龄无关。同时使用核型分析和染色体微阵列分析，而不是单独使用核型分析，可减轻与培养相关的偏差并提高PPV。生物学和方法学因素均导致NIPT检测RCA的PPV较低。尽管PPV较低，但NIPT提示有RCA的妊娠显示出胎儿丢失、小于胎龄儿和单亲二体的风险升高，尽管没有早产风险。因此，NIPT检测到的RCA在风险分层和妊娠管理方面仍具有临床意义。
