彭海山 黄华洁 杨洁霞 侯亚萍 郭芳芳 齐一鸣 尹爱华

【摘要】 目的   探讨无创产前基因检测（NIPT）在产前筛查中的临床应用价值。方法 收集23 852例孕妇检测指征和结果，对提示高风险孕妇建议进一步行有创产前诊断，对比分析NIPT与核型或微阵列结果。结果   23 852例孕妇的检测指征中，以血清学筛查临界风险（30.18%）及高风险（26.14%）居多。NIPT共检出446例高风险病例，常见的21?、18?、13?三体综合征占高风险总例数的37.39%。其中有226例选择进一步行有创产前诊断，确诊21?三体综合征高风险67例、18?三体综合征14例、13?三体综合征12例、性染色体异常54例、染色体缺失或重复57例、其他染色体数目异常21例以及多条染色体异常1例，NIPT诊断21?三体综合征的PPV为88.06%，18?三体综合征的PPV为78.57%，13?三体综合征的PPV为33.33%，性染色体的阳性预测值（PPV）为33.33%，染色体缺失/重复的PPV为15.79%，其他染色体数目异常的PPV为4.76%。21?、18?、13?三体综合征的复合PPV达79.57%。在对NIPT低风险孕妇的随访中检出8例染色体异常病例。结论   NIPT对21?、18?、13?三体综合征具有较高的检测效能，但是仍然存在假阳性与假阴性的局限性，仅可作为筛查手段，在臨床工作中应做好NIPT检测前和检测后的咨询工作。

【关键词】  无创产前基因筛查;应用价值;指征;阳性预测值

【Abstract】 ObjectiveTo assess the application value of non?invasive prenatal testing （NIPT） in prenatal screening. MethodsThe testing indications and results of 23 852 pregnant women who underwent NIPT were collected. Those with a potential high risk further received invasive prenatal diagnosis. The detection results between NIPT and karyotyping and chromosomal microarray analysis （CMA） were statistically compared. Results    Among the testing indications of 23 852 pregnant women，the critical risk （30.18%） and high risk （26.14%） of serum screening accounted for the dominant percentage. NIPT demonstrated 446 patients were high risk cases and 37.39% of them were diagnosed with 21?，18? and 13?trisomy syndrome. Among them，226 cases chose to further receive invasive prenatal diagnosis and 67 women were diagnosed with high?risk 21?trisomy syndrome，14 with 18?trisomy syndrome，12 with 13?trisomy syndrome，54 with sex chromosomal abnormality，57 with chromosomal deletion/duplication，21 with other chromosomal abnormality and 1 with multiple chromosomal abnormalities. The positive predictive value of NIPT in the diagnosis of 21?trisomy syndrome was 88.06%，78.57% for 18?trisomy syndrome，33.33% for 13?trisomy syndrome，33.33% for sex chromosomal abnormality，15.79% for chromosomal deletion/duplication and 4.76% for other chromosomal abnormality，respectively. The composite positive predictive value for 21?，18? and 13?trisomy syndrome was up to 79.57%. During subsequent follow?up，chromosomal abnormality was detected in 8 low?risk pregnant women by NIPT. ConclusionsNIPT possesses relatively high efficiency in the diagnosis of 21?，18? and 13?trisomy syndrome，whereas it still yields false negative/positive outcomes. Therefore，NIPT can serve as a screening tool. Comprehensive pre? and post?NIPT counseling should be performed in clinical practice.

【Key words】 Non?invasive prenatal testing;Application value;Indication;Positive predictive value

染色体异常是出生缺陷的最常见原因之一[1]。我国每年约有10万例染色体异常患儿出生，出生缺陷成为影响我国人口素质及群体健康水平的公共卫生问题[2?3]。预防出生缺陷的最有效手段是使用产前筛查与产前诊断干预[1，3?4]。近年产前诊断模式逐步向减少低危人群的有创检查，提高高危人群的有效检出发展[5]。……