高通量基因测序在胎儿染色体非整倍体产前筛查中的应用 [中文引用][英文引用]

目的 评价高通量基因测序在胎儿染色体非整倍体产前筛查中的临床应用价值。方法 采用高通量基因测序对3186例孕妇进行胎儿染色体非整倍体无创产前筛查（non-invasive prenatal screening，NIPS），高风险者进行侵入性产前染色体核型分析验证和随访。结果 3186例孕妇中NIPS发现胎儿染色体异常43例，高风险率为1.35%（43/3186），其中21-三体高风险18例，18-三体高风险5例，13-三体高风险4例和其他染色体异常高风险16例。高风险病例中产前诊断确诊32例，其中确诊21-三体17例，18-三体3例，13-三体3例和其他染色体异常9例。NIPS对21-三体、18-三体、13-三体和其他染色体异常的敏感度均为100%，特异度分别为99.97%、99.94%、99.97%和99.78%，总阳性预测值为74.42%（32/43），总假阳性率0.35%（11/3186）。结论 NIPS具有灵敏度高、特异性强、无创安全等优点，有较高的临床应用价值。但NIPS提示高风险，必须通过侵入性产前诊断进行染色体核型分析，低风险孕妇也要加强孕期监测，避免漏诊。

Objective To evaluate the clinical application value of high-throughput gene sequencing for prenatal screening of fetal chromosomal aneuploidy. Method Non-invasive prenatal screening(NIPS) of fetal chromosomal aneuploidy in 3186 pregnant women by high-throughput gene sequencing. High-risk result were verified by invasive prenatal chromosomal karyotype analysis and followed up. Results Among the 3186 pregnant women, 43 cases of fetal chromosomal abnormalities were found by NIPS, the high risk rate is 1.35% (43/3186), including 18 cases of high risk 21 trisomy, 5 cases of high risk 18 trisomy,4 cases of high risk trisomy 13 and 16 cases of other chromosomal abnormalities. 32 cases of prenatal diagnosis were diagnosed in high risk cases, including 17 cases were diagnosed of 21 trisomy, 3 cases of 18 trisomy, 3 cases of trisomy 13 and 9 cases of other chromosomal abnormalities. The sensitivity for trisomy 21, trisomy 18, trisomy 13 and other chromosomal abnormalities were 100%, the specificity were 99.97%, 99.94%, 99.97% and 99.78%, respectively. The total positive predictive value was 74.42% (32/43), and the total false positive rate was 0.35% (11/3186). Conclusion NIPS has the advantages of high sensitivity and specificity, non-invasive safety, and has a good clinical application value. However, NIPS indicated high risk must be performed through invasive prenatal diagnosis by chromosomal karyotype analysis and the low risk pregnant women should also strengthen pregnancy monitoring to avoid missed diagnosis.