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Abstract：
OBJECTIVE: To evaluate the clinical value of positive copy number variations (CNVs) results by non-invasive prenatal testing (NIPT) without fetal ultrasonography-identified structural anomalies, especially with several known CNVs results.
METHODS: A total of 135,981 results of NIPT performed between April 1, 2017, and March 31, 2020, enrolled in the free NIPT service program implemented by the local government were retrospectively analyzed. Of these, 87 cases with positive NIPT screens for CNVs and no fetal ultrasonography-identified anomalies were recalled and provided genetic counseling. After obtaining full informed consent, these cases were provided invasive prenatal diagnosis by karyotyping and chromosomal microarray analysis (CMA)/copy number variation sequencing (CNV-seq) with follow-up. One case was lost, while 86 cases were successfully followed up.
RESULTS: A total of 44 (50.6%) cases underwent invasive prenatal diagnosis, of which six cases were detected with abnormal karyotype. CMA/CNV-Seq revealed 11 fetuses with positive results for CNVs, among whom eight were consistent with NIPT results, two were partially consistent, one was inconsistent, and positive predictive value (PPV) was 22.7% (10/44). For known CNVs, PPVs were 20% (15q11.2-q13 microdeletion) and 33.3% (5p end deletions). Among 11 pregnant women with positive prenatal diagnosis, seven were confirmed to have pathogenic CNVs in their fetuses; four had CNVs of unknown clinical significance.
CONCLUSIONS: Even in pregnancies without ultrasonography-identified anomalies, a positive NIPT screen for CNVs must be interpreted with caution and validated by additional diagnostic study.
METHODS: A total of 135,981 results of NIPT performed between April 1, 2017, and March 31, 2020, enrolled in the free NIPT service program implemented by the local government were retrospectively analyzed. Of these, 87 cases with positive NIPT screens for CNVs and no fetal ultrasonography-identified anomalies were recalled and provided genetic counseling. After obtaining full informed consent, these cases were provided invasive prenatal diagnosis by karyotyping and chromosomal microarray analysis (CMA)/copy number variation sequencing (CNV-seq) with follow-up. One case was lost, while 86 cases were successfully followed up.
RESULTS: A total of 44 (50.6%) cases underwent invasive prenatal diagnosis, of which six cases were detected with abnormal karyotype. CMA/CNV-Seq revealed 11 fetuses with positive results for CNVs, among whom eight were consistent with NIPT results, two were partially consistent, one was inconsistent, and positive predictive value (PPV) was 22.7% (10/44). For known CNVs, PPVs were 20% (15q11.2-q13 microdeletion) and 33.3% (5p end deletions). Among 11 pregnant women with positive prenatal diagnosis, seven were confirmed to have pathogenic CNVs in their fetuses; four had CNVs of unknown clinical significance.
CONCLUSIONS: Even in pregnancies without ultrasonography-identified anomalies, a positive NIPT screen for CNVs must be interpreted with caution and validated by additional diagnostic study.
摘要：
目的：评估无胎儿超声诊断结构异常的非侵入性产前检测（NIPT）阳性拷贝数变异（CNVs）结果的临床价值，特别是与几个已知的CNVs结果。
方法：回顾性分析2017年4月1日至2020年3月31日期间参加地方政府实施的免费NIPT服务计划的135,981例NIPT结果。其中,召回了87例CNVNIPT筛查阳性且无胎儿超声检查异常的病例，并提供了遗传咨询。在获得完全知情同意后，通过核型分析和染色体微阵列分析(CMA)/拷贝数变异测序(CNV-seq)对这些病例进行侵入性产前诊断,并进行随访.一个案子丢了,86例成功随访。
结果：共有44例（50.6%）进行了侵入性产前诊断，其中6例检出核型异常。CMA/CNV-Seq显示11个胎儿的CNV阳性结果，其中8人与NIPT结果一致，两个部分一致，一个是不一致的，阳性预测值（PPV）为22.7%（10/44）。对于已知的CNVs,PPV为20%(15q11.2-q13微缺失)和33.3%(5p末端缺失)。在11名产前诊断阳性的孕妇中，7例被证实在其胎儿中有致病性CNVs;4例具有未知临床意义的CNVs.
结论：即使在没有超声诊断异常的妊娠中，CNVs的NIPT筛查阳性必须谨慎解读,并通过其他诊断研究进行验证.
方法：回顾性分析2017年4月1日至2020年3月31日期间参加地方政府实施的免费NIPT服务计划的135,981例NIPT结果。其中,召回了87例CNVNIPT筛查阳性且无胎儿超声检查异常的病例，并提供了遗传咨询。在获得完全知情同意后，通过核型分析和染色体微阵列分析(CMA)/拷贝数变异测序(CNV-seq)对这些病例进行侵入性产前诊断,并进行随访.一个案子丢了,86例成功随访。
结果：共有44例（50.6%）进行了侵入性产前诊断，其中6例检出核型异常。CMA/CNV-Seq显示11个胎儿的CNV阳性结果，其中8人与NIPT结果一致，两个部分一致，一个是不一致的，阳性预测值（PPV）为22.7%（10/44）。对于已知的CNVs,PPV为20%(15q11.2-q13微缺失)和33.3%(5p末端缺失)。在11名产前诊断阳性的孕妇中，7例被证实在其胎儿中有致病性CNVs;4例具有未知临床意义的CNVs.
结论：即使在没有超声诊断异常的妊娠中，CNVs的NIPT筛查阳性必须谨慎解读,并通过其他诊断研究进行验证.
