Abstract：
Background and Objectives: Non-invasive prenatal testing (NIPT) has been confirmed as the most accurate screening test for trisomies 21, 18, 13, sex chromosomes aneuploidies and several microdeletions. This study aimed to assess the accuracy of cell free DNA testing based on low-level whole-genome sequencing to screen for these chromosomal abnormalities and to evaluate the clinical performance of NIPT. Materials and Methods: 380 consecutive cases from a single genetic center, from Western Romania were included in this retrospective study. Cell-free nucleic acid extraction from maternal blood, DNA sequencing and analysis of sequenced regions were performed by BGI Hong Kong and Invitae USA to determine the risk of specific fetal chromosomal abnormalities. In high-risk cases the results were checked by direct analysis of fetal cells obtained by invasive methods: 6 chorionic villus sampling and 10 amniocenteses followed by combinations of QF-PCR, karyotyping and aCGH. Results: NIPT results indicated low risk in 95.76% of cases and high risk in 4.23%. Seven aneuploidies and one microdeletion were confirmed, the other results were found to be a false-positive. A gestational age of up to 22 weeks had no influence on fetal fraction. There were no significant differences in fetal fraction across the high and low risk groups. Conclusions: This is the first study in Romania to report the NIPT results. The confirmation rate was higher for autosomal aneuploidies compared to sex chromosome aneuploidies and microdeletions. All cases at risk for trisomy 21 were confirmed. Only one large fetal microdeletion detected by NIPT has been confirmed. False positive NIPT results, not confirmed by invasive methods, led to the decision to continue the pregnancy. The main limitation of the study is the small number of patients included. NIPT can be used as a screening method for all pregnancies, but in high-risk cases, an invasive confirmation test was performed.
摘要：
背景和目的：非侵入性产前检测（NIPT）已被确认为21、18、13三体，性染色体非整倍体和几种微缺失的最准确的筛查测试。这项研究旨在评估基于低水平全基因组测序的无细胞DNA检测的准确性，以筛选这些染色体异常并评估NIPT的临床性能。材料与方法：来自单个遗传中心的380例连续病例，来自罗马尼亚西部的患者被纳入本回顾性研究.从母体血液中提取无细胞核酸，华大基因香港和InvitaeUSA进行了DNA测序和测序区域的分析，以确定特定胎儿染色体异常的风险。在高风险病例中，通过直接分析通过侵入性方法获得的胎儿细胞来检查结果：6次绒毛膜绒毛取样和10次羊膜穿刺术，然后进行QF-PCR组合，核型分析和aCGH。结果：NIPT结果显示95.76％的病例风险低，4.23％的病例风险高。证实了七个非整倍体和一个微缺失，其他结果被发现是假阳性。长达22周的胎龄对胎儿分数没有影响。高危组和低危组的胎儿分数没有显着差异。结论：这是罗马尼亚首次报道NIPT结果的研究。与性染色体非整倍体和微缺失相比，常染色体非整倍体的确认率更高。所有有21三体风险的病例均得到确认。仅确认了通过NIPT检测到的一个大的胎儿微缺失。NIPT假阳性结果,没有被侵入性方法证实，导致了继续怀孕的决定。该研究的主要限制是纳入的患者数量少。NIPT可用作所有妊娠的筛查方法，但是在高风险的情况下，进行了侵入性确认试验.
