Abstract：
OBJECTIVE: To evaluate cell-free DNA (cfDNA) testing as a non-invasive approach to detecting aneuploidies in clinical miscarriages.
METHODS: A retrospective cohort study of women with pregnancy loss.
METHODS: Hospitals and genetic analysis laboratories.
METHODS: Pregnancy losses in the period 2021-2022.
METHODS: Results derived from non-invasive cfDNA testing (Veriseq NIPT Solution V2) of maternal blood and invasive analysis of products of conception (POC) (Ion ReproSeq) compared in 120 women who suffered a miscarriage.
METHODS: Concordance rate results, cfDNA testing performance, non-informative rate (NIR) and fetal fraction (FF).
RESULTS: We found no significant differences in the NIR between invasive (iPOC) and non-invasive (niPOC) analysis of POC (10.0% [12/120] versus 16.7% [20/120]). Of 120 samples, 90 provided an informative result in iPOC and niPOC groups (75%). cfDNA analysis correctly identified 74/87 (85.1%) samples (excluding triploidies). Sensitivity and specificity were 79.4% and 100%, respectively; all discordant cases were female. A binomial logistic model suggested fetal sex as the only variable influencing the concordance rate (P = 0.035). A Y-chromosome-based FF estimate allowed the optimal reclassification of cfDNA of non-informative male fetuses and a more accurate evaluation of cfDNA testing performance. The difference between the two FF estimates (native algorithm and Y-chromosome-based) suggests that female non-concordant cases may represent non-informative cases.
CONCLUSIONS: Cell-free DNA-based testing provides a non-invasive approach to determining the genetic cause of clinical miscarriage.
METHODS: A retrospective cohort study of women with pregnancy loss.
METHODS: Hospitals and genetic analysis laboratories.
METHODS: Pregnancy losses in the period 2021-2022.
METHODS: Results derived from non-invasive cfDNA testing (Veriseq NIPT Solution V2) of maternal blood and invasive analysis of products of conception (POC) (Ion ReproSeq) compared in 120 women who suffered a miscarriage.
METHODS: Concordance rate results, cfDNA testing performance, non-informative rate (NIR) and fetal fraction (FF).
RESULTS: We found no significant differences in the NIR between invasive (iPOC) and non-invasive (niPOC) analysis of POC (10.0% [12/120] versus 16.7% [20/120]). Of 120 samples, 90 provided an informative result in iPOC and niPOC groups (75%). cfDNA analysis correctly identified 74/87 (85.1%) samples (excluding triploidies). Sensitivity and specificity were 79.4% and 100%, respectively; all discordant cases were female. A binomial logistic model suggested fetal sex as the only variable influencing the concordance rate (P = 0.035). A Y-chromosome-based FF estimate allowed the optimal reclassification of cfDNA of non-informative male fetuses and a more accurate evaluation of cfDNA testing performance. The difference between the two FF estimates (native algorithm and Y-chromosome-based) suggests that female non-concordant cases may represent non-informative cases.
CONCLUSIONS: Cell-free DNA-based testing provides a non-invasive approach to determining the genetic cause of clinical miscarriage.
摘要：
目的：评估无细胞DNA（cfDNA）检测作为临床流产中检测非整倍体的非侵入性方法。
方法：一项妊娠流产妇女的回顾性队列研究。
方法：医院和基因分析实验室。
方法：2021-2022年期间的妊娠损失。
方法：比较了120例流产妇女的母体血液的非侵入性cfDNA测试（VeriseqNIPTSolutionV2）和受孕产物（POC）的侵入性分析（IonReproSeq）得出的结果。
方法：一致性结果，cfDNA测试性能，无信息率（NIR）和胎儿分数（FF）。
结果：我们发现P0C的侵入性（iP0C）和非侵入性（niP0C）分析的NIR无显著差异（10.0%[12/120]对16.7%[20/120]）。在120个样本中，90在iPOC和niPOC组中提供了信息性结果(75%)。cfDNA分析正确鉴定了74/87（85.1％）样品（不包括三倍体）。敏感性和特异性分别为79.4%和100%,分别；所有不和谐病例均为女性。二项逻辑模型表明胎儿性别是影响一致性率的唯一变量（P=0.035）。基于Y染色体的FF估计允许对无信息的男性胎儿的cfDNA进行最佳重新分类，并对cfDNA测试性能进行更准确的评估。两个FF估计（原生算法和基于Y染色体）之间的差异表明，女性不一致病例可能代表非信息病例。
结论：基于无细胞DNA的检测为确定临床流产的遗传原因提供了一种非侵入性方法。
方法：一项妊娠流产妇女的回顾性队列研究。
方法：医院和基因分析实验室。
方法：2021-2022年期间的妊娠损失。
方法：比较了120例流产妇女的母体血液的非侵入性cfDNA测试（VeriseqNIPTSolutionV2）和受孕产物（POC）的侵入性分析（IonReproSeq）得出的结果。
方法：一致性结果，cfDNA测试性能，无信息率（NIR）和胎儿分数（FF）。
结果：我们发现P0C的侵入性（iP0C）和非侵入性（niP0C）分析的NIR无显著差异（10.0%[12/120]对16.7%[20/120]）。在120个样本中，90在iPOC和niPOC组中提供了信息性结果(75%)。cfDNA分析正确鉴定了74/87（85.1％）样品（不包括三倍体）。敏感性和特异性分别为79.4%和100%,分别；所有不和谐病例均为女性。二项逻辑模型表明胎儿性别是影响一致性率的唯一变量（P=0.035）。基于Y染色体的FF估计允许对无信息的男性胎儿的cfDNA进行最佳重新分类，并对cfDNA测试性能进行更准确的评估。两个FF估计（原生算法和基于Y染色体）之间的差异表明，女性不一致病例可能代表非信息病例。
结论：基于无细胞DNA的检测为确定临床流产的遗传原因提供了一种非侵入性方法。
