NIPT检出罕见常染色体三体的高风险：产前诊断与妊娠结局
该回顾性研究分析了2020年5月至2024年8月期间在本中心接受NIPT的20796例孕妇，其中0.26%（55/20796）被确定为罕见常染色体三体（RATs）高风险。产前诊断44例，阳性预测值（PPV）为4.55%。结论认为NIPT对RATs的PPV低但不良结局风险高，需结合产前诊断与超声监测评估胎儿预后。
要点
- NIPT筛查RATs高风险率为0.26%，产前诊断PPV仅4.55%。
- CMA未发现异常的36例中，38.89%出现不良妊娠结局。
- 羊细胞产前诊断的嵌合型RATs不一定与明显出生后表型相关。
核心结论
- NIPT筛查RATs的阳性预测值低，但不良妊娠结局风险高，应建议产前诊断并结合超声监测。
研究设计与样本
- 回顾性分析2020年5月至2024年8月在本中心接受NIPT的20796例孕妇，其中55例RATs高风险。
- 采用靶向扩增子测序筛查单亲二体（UPD）相关印记障碍，并对所有高风险妊娠建议产前诊断和妊娠结局随访。
主要发现
- 20796例中0.26%（55/20796）为RATs高风险，44例接受产前诊断，PPV为4.55%。
- 4例确诊母源拷贝数变异，其中3例传递给胎儿。
- 23例中未检测到UPD相关印记障碍。
- 2例嵌合型三体在CMA上嵌合水平相似但临床结局不同。
- 36例产前CMA未发现异常者中，38.89%出现不良结局。
关键数值与推荐
- 拷贝数（CN）≥2.4提示母源重复高风险，CN≤1.6提示母源缺失。
- 靶向扩增子测序用于筛查UPD相关印记障碍。
临床怎么用
- 对NIPT提示RATs高风险的孕妇应建议产前诊断，并结合超声监测评估胎儿预后。
- 产前诊断时应考虑母源拷贝数变异及UPD相关印记障碍的筛查。
以上解读依据论文摘要（全文未开放获取或许可不允许翻译转载）。
原文
OBJECTIVE: To investigate the incidence, positive predictive value (PPV) and pregnancy outcomes of rare autosomal trisomies (RATs) identified by non-invasive prenatal testing (NIPT). METHOD: A retrospective analysis of pregnancies who underwent NIPT at our center between May 2020 and August 2024 and received high-risk RATs results. A copy number (CN) ≥ 2.4 indicated high-risk for maternal duplications, while a CN ≤ 1.6 correlated with maternal deletion. Targeted amplicon sequencing was utilized to screen for uniparental disomy (UPD)-related imprinting disorders. Prenatal diagnosis and pregnancy outcome follow-up were recommended for all high-risk pregnancies. RESULTS: Among 20,796 pregnancies screened, 0.26% (55/20,796) were identified as high-risk for RATs. Prenatal diagnosis was performed in 44 cases, with a PPV of 4.55%. Maternal copy number variations were confirmed in four cases, three of which were transmitted to the fetus. No UPD-related imprinting disorders were detected in the 23 cases. Two cases of mosaic trisomy showed similar levels of mosaicism on chromosomal microarray analysis (CMA) but had divergent clinical outcomes. Among 36 cases with no abnormalities detected by prenatal CMA, 38.89% had adverse outcomes. CONCLUSION: NIPT for RATs has a low PPV, but the risk of adverse outcomes is high. Mosaic RATs identified via amniocyte-based prenatal diagnosis do not always correlate with an obvious postnatal phenotype. Integrating prenatal diagnosis with ultrasound monitoring is essential for fetal prognosis.
引用
- Jiang Z, Wang W, Zhang Y, et al. High Risk for Rare Autosomal Trisomies Detected by Non-Invasive Prenatal Testing: Prenatal Diagnosis and Pregnancy Outcomes. Prenat Diagn. 2026. PMID: 42142393. doi:10.1002/pd.70181
供执业医师工作参考，不替代临床判断；数值与分级以指南原文为准。