Abstract：
OBJECTIVE: To investigate the detectability of noninvasive prenatal screening (NIPS) with conventional sequencing depth to detect fetal copy number variants.
METHODS: We performed a retrospective study in a total of 19 144 pregnant women. Their cell-free plasma DNA were assessed for trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidies, and genome-wide copy number variants by NIPS at conventional sequencing depth.
RESULTS: Three hundred seventy-four cases (2.0%, 374/19 144) with abnormal results were detected, which including 84 cases (0.4%, 84/19 144) with high risk of trisomy 21, 18, and 13, 90 cases (0.5%, 90/19 144) with high risk of sex chromosome abnormalities (SCA), and 44 cases (0.2%, 44/19 144) with high risk of other chromosome aneuploidies. One hundred fifty-six cases (0.8%, 156/19 144) with high risk of copy number variations (CNVs) were also detected. In following prenatal diagnosis, composite positive predictive value (PPV) of trisomy 21, 18, and 13 was 69.6% (48/69). The PPV of SCAs was 37.3% (19/51). And the PPVs for CNVs was detected as 51.0% (<5 Mb), 71.4% (5 Mb ≤ CNV ≤10 Mb), 56.5% (>10 Mb). Finally, a follow-up about the pregnancy outcomes were conducted for all available cases.
CONCLUSIONS: NIPS yielded high PPVs for trisomy 21, 18, and 13 aneuploidies and moderate PPVs for SCAs and CNVs. The screening effectiveness was closely related to the size of CNV fragments. Larger CNVs, especially larger than 5 Mb, could be detected more accurately by NIPS in our analytic technique. Meanwhile, diagnostic confirmation by microarray analysis was highly recommended.
METHODS: We performed a retrospective study in a total of 19 144 pregnant women. Their cell-free plasma DNA were assessed for trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidies, and genome-wide copy number variants by NIPS at conventional sequencing depth.
RESULTS: Three hundred seventy-four cases (2.0%, 374/19 144) with abnormal results were detected, which including 84 cases (0.4%, 84/19 144) with high risk of trisomy 21, 18, and 13, 90 cases (0.5%, 90/19 144) with high risk of sex chromosome abnormalities (SCA), and 44 cases (0.2%, 44/19 144) with high risk of other chromosome aneuploidies. One hundred fifty-six cases (0.8%, 156/19 144) with high risk of copy number variations (CNVs) were also detected. In following prenatal diagnosis, composite positive predictive value (PPV) of trisomy 21, 18, and 13 was 69.6% (48/69). The PPV of SCAs was 37.3% (19/51). And the PPVs for CNVs was detected as 51.0% (<5 Mb), 71.4% (5 Mb ≤ CNV ≤10 Mb), 56.5% (>10 Mb). Finally, a follow-up about the pregnancy outcomes were conducted for all available cases.
CONCLUSIONS: NIPS yielded high PPVs for trisomy 21, 18, and 13 aneuploidies and moderate PPVs for SCAs and CNVs. The screening effectiveness was closely related to the size of CNV fragments. Larger CNVs, especially larger than 5 Mb, could be detected more accurately by NIPS in our analytic technique. Meanwhile, diagnostic confirmation by microarray analysis was highly recommended.
摘要：
目的：探讨常规测序深度非侵入性产前筛查（NIPS）检测胎儿拷贝数变异的可检测性。
方法：我们对总共19144名孕妇进行了回顾性研究。评估了他们的无细胞血浆DNA的21三体，18三体，13三体，性染色体非整倍体，和通过NIPS在常规测序深度下的全基因组拷贝数变异。
结果：三百七十四例（2.0％，374/19144）检测到异常结果，其中包括84例(0.4%，84/19144），具有21、18和13三体的高风险，90例（0.5％，90/19144）具有性染色体异常（SCA）的高风险，和44例(0.2%，44/19144）具有其他染色体非整倍体的高风险。一百五十六例(百分之零点八,156/19144）也检测到了拷贝数变异（CNVs）的高风险。在产前诊断之后，21、18和13三体的复合阳性预测值(PPV)为69.6%(48/69).SCA的PPV为37.3%(19/51)。CNVs的PPVs检测为51.0%(<5Mb)，71.4%(5Mb≤CNV≤10Mb),56.5%(>10Mb)。最后,我们对所有可用病例进行了妊娠结局的随访.
结论：对于21、18和13三体非整倍体，NIPS产生高PPV，对于SCA和CNV产生中等PPV。筛选效果与CNV片段大小密切相关。较大的CNVs,特别是大于5Mb，在我们的分析技术中，NIPS可以更准确地检测到。同时,强烈建议通过微阵列分析进行诊断确认.
方法：我们对总共19144名孕妇进行了回顾性研究。评估了他们的无细胞血浆DNA的21三体，18三体，13三体，性染色体非整倍体，和通过NIPS在常规测序深度下的全基因组拷贝数变异。
结果：三百七十四例（2.0％，374/19144）检测到异常结果，其中包括84例(0.4%，84/19144），具有21、18和13三体的高风险，90例（0.5％，90/19144）具有性染色体异常（SCA）的高风险，和44例(0.2%，44/19144）具有其他染色体非整倍体的高风险。一百五十六例(百分之零点八,156/19144）也检测到了拷贝数变异（CNVs）的高风险。在产前诊断之后，21、18和13三体的复合阳性预测值(PPV)为69.6%(48/69).SCA的PPV为37.3%(19/51)。CNVs的PPVs检测为51.0%(<5Mb)，71.4%(5Mb≤CNV≤10Mb),56.5%(>10Mb)。最后,我们对所有可用病例进行了妊娠结局的随访.
结论：对于21、18和13三体非整倍体，NIPS产生高PPV，对于SCA和CNV产生中等PPV。筛选效果与CNV片段大小密切相关。较大的CNVs,特别是大于5Mb，在我们的分析技术中，NIPS可以更准确地检测到。同时,强烈建议通过微阵列分析进行诊断确认.
