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Abstract：
BACKGROUND: Introduction of cell-free fetal DNA (cff-DNA) testing in maternal blood opened possibilities to improve the performance of combined first-trimester screening (cFTS) in terms of better detection of trisomies and lowering invasive testing rate. The use of new molecular methods, such as chromosomal microarray analysis (CMA) and next-generation sequencing (NGS), has shown benefits in prenatal diagnosis of chromosomal and genetic diseases, which are not detectable with cff-DNA screening, but require an invasive procedure.
METHODS: The objective of this study was to evaluate prospectively during two years performance of CMA and NGS in high-risk pregnancies. Initially, we investigated 14,566 singleton pregnancies with cFTS. A total of 334 high-risk pregnancies were selected for CMA diagnostic performance evaluation and 28 cases of highly dysmorphic fetuses for NGS analysis. CMA study group was divided into two groups based on the indications for testing; group A patients with high-risk for trisomies after cFTS, but normal ultrasound and group B patients who met criteria for CMA as a first-tier diagnostic test.
RESULTS: The diagnostic yield of CMA was overall 3.6% (1.6% in Group A and 6.0% in Group B). In NGS analysis group, we report diagnostic yield of 17.9%.
CONCLUSIONS: The use of CMA in high-risk pregnancies is justified and provides relevant clinical information in 3.6% of the cases. NGS analysis in fetuses with multiple anomalies shows promising results, but more investigations are needed for a better understanding of practical applications of this molecular diagnosis method in prenatal settings.
METHODS: The objective of this study was to evaluate prospectively during two years performance of CMA and NGS in high-risk pregnancies. Initially, we investigated 14,566 singleton pregnancies with cFTS. A total of 334 high-risk pregnancies were selected for CMA diagnostic performance evaluation and 28 cases of highly dysmorphic fetuses for NGS analysis. CMA study group was divided into two groups based on the indications for testing; group A patients with high-risk for trisomies after cFTS, but normal ultrasound and group B patients who met criteria for CMA as a first-tier diagnostic test.
RESULTS: The diagnostic yield of CMA was overall 3.6% (1.6% in Group A and 6.0% in Group B). In NGS analysis group, we report diagnostic yield of 17.9%.
CONCLUSIONS: The use of CMA in high-risk pregnancies is justified and provides relevant clinical information in 3.6% of the cases. NGS analysis in fetuses with multiple anomalies shows promising results, but more investigations are needed for a better understanding of practical applications of this molecular diagnosis method in prenatal settings.
摘要：
背景：在母体血液中引入无细胞胎儿DNA（cff-DNA）检测为改善联合早孕期筛查（cFTS）在更好地检测三体和降低侵入性检测率方面的性能开辟了可能性。使用新的分子方法，如染色体微阵列分析（CMA）和下一代测序（NGS），在染色体和遗传疾病的产前诊断中显示出优势，用cff-DNA筛查无法检测到，但需要侵入性的程序.
方法：本研究的目的是前瞻性评估CMA和NGS在高危妊娠中的两年表现。最初，我们用cFTS调查了14566例单胎妊娠。总共选择了334例高风险妊娠进行CMA诊断性能评估，并选择了28例高度畸形胎儿进行NGS分析。CMA研究组根据检测的适应症分为两组;A组患者在cFTS后出现三体综合征的高风险,但正常超声和符合CMA标准的B组患者作为一级诊断测试。
结果：CMA的诊断率总体为3.6%（A组为1.6%，B组为6.0%）。在NGS分析组中，我们报告的诊断率为17.9%。
结论：在高危妊娠中使用CMA是合理的，并在3.6%的病例中提供了相关的临床信息。具有多个异常的胎儿的NGS分析显示出有希望的结果，但需要更多的研究才能更好地了解这种分子诊断方法在产前环境中的实际应用.
方法：本研究的目的是前瞻性评估CMA和NGS在高危妊娠中的两年表现。最初，我们用cFTS调查了14566例单胎妊娠。总共选择了334例高风险妊娠进行CMA诊断性能评估，并选择了28例高度畸形胎儿进行NGS分析。CMA研究组根据检测的适应症分为两组;A组患者在cFTS后出现三体综合征的高风险,但正常超声和符合CMA标准的B组患者作为一级诊断测试。
结果：CMA的诊断率总体为3.6%（A组为1.6%，B组为6.0%）。在NGS分析组中，我们报告的诊断率为17.9%。
结论：在高危妊娠中使用CMA是合理的，并在3.6%的病例中提供了相关的临床信息。具有多个异常的胎儿的NGS分析显示出有希望的结果，但需要更多的研究才能更好地了解这种分子诊断方法在产前环境中的实际应用.
