Abstract：
Cell-free fetal DNA screening is routinely offered to pregnant individuals to screen for aneuploidies. Although cell-free DNA screening is consistently more accurate than multiple-marker screening, it sometimes fails to yield a result. These test failures and their clinical implications are poorly described in the literature. Some studies suggest that a failed cell-free DNA screening result is associated with increased likelihood of cytogenetic abnormalities.
This study aimed to assess the association between a failed cell-free DNA test and common aneuploidies. The objectives were to determine: (1) the proportion of test failures on first and subsequent attempts, and (2) whether a failed cell-free DNA screen on first attempt is associated with increased likelihood of common aneuploidies (trisomies 21, 18, and 13, and sex chromosome aneuploidies).
This was a population-based retrospective cohort study using data from Ontario\'s prescribed maternal and child registry, Better Outcomes Registry and Network Ontario. The study included all singleton pregnancies in Ontario with an estimated date of delivery from September 1, 2016 to March 31, 2019 that had a cell-free DNA screening record in the registry. Specific outcomes (trisomies 21, 18, and 13, and sex chromosome aneuploidies) of pregnancies with a failed cell-free DNA screen on first attempt were compared with those of pregnancies with low-risk cell-free DNA-screening results using modified Poisson regression adjusted for funding status (publicly funded vs self-paid), gestational age at screening, method of conception, and maternal age for autosomal aneuploidies.
Our cohort included 35,146 pregnancies that had cell-free DNA screening during the study period. The overall cell-free DNA screening failure rate was 4.8% on first attempt and 2.2% after multiple attempts. An abnormal cytogenetic result for trisomies 21, 18, and 13, or sex chromosome aneuploidies was identified in 19.4% of pregnancies with a failed cell-free DNA screening for which cytogenetic testing was performed. Pregnancies with a failed cell-free DNA screen on first attempt had a relative risk of 130.3 (95% confidence interval, 64.7-262.6) for trisomy 21, trisomy 18, or trisomy 13, and a risk difference of 5.4% (95% confidence interval, 2.6-8.3), compared with pregnancies with a low-risk result. The risk of sex chromosome aneuploidies was not significantly greater in pregnancies with a failed result compared with pregnancies with a low-risk result (relative risk, 2.7; 95% confidence interval, 0.9-7.9; relative difference, 1.2%; 95% confidence interval, -0.9 to 3.2).
Cell-free DNA screening test failures are relatively common. Although repeated testing improves the likelihood of an informative result, pregnancies with a failed cell-free DNA screen upon first attempt remain at increased risk for common autosomal aneuploidies, but not sex chromosome aneuploidies.
This study aimed to assess the association between a failed cell-free DNA test and common aneuploidies. The objectives were to determine: (1) the proportion of test failures on first and subsequent attempts, and (2) whether a failed cell-free DNA screen on first attempt is associated with increased likelihood of common aneuploidies (trisomies 21, 18, and 13, and sex chromosome aneuploidies).
This was a population-based retrospective cohort study using data from Ontario\'s prescribed maternal and child registry, Better Outcomes Registry and Network Ontario. The study included all singleton pregnancies in Ontario with an estimated date of delivery from September 1, 2016 to March 31, 2019 that had a cell-free DNA screening record in the registry. Specific outcomes (trisomies 21, 18, and 13, and sex chromosome aneuploidies) of pregnancies with a failed cell-free DNA screen on first attempt were compared with those of pregnancies with low-risk cell-free DNA-screening results using modified Poisson regression adjusted for funding status (publicly funded vs self-paid), gestational age at screening, method of conception, and maternal age for autosomal aneuploidies.
Our cohort included 35,146 pregnancies that had cell-free DNA screening during the study period. The overall cell-free DNA screening failure rate was 4.8% on first attempt and 2.2% after multiple attempts. An abnormal cytogenetic result for trisomies 21, 18, and 13, or sex chromosome aneuploidies was identified in 19.4% of pregnancies with a failed cell-free DNA screening for which cytogenetic testing was performed. Pregnancies with a failed cell-free DNA screen on first attempt had a relative risk of 130.3 (95% confidence interval, 64.7-262.6) for trisomy 21, trisomy 18, or trisomy 13, and a risk difference of 5.4% (95% confidence interval, 2.6-8.3), compared with pregnancies with a low-risk result. The risk of sex chromosome aneuploidies was not significantly greater in pregnancies with a failed result compared with pregnancies with a low-risk result (relative risk, 2.7; 95% confidence interval, 0.9-7.9; relative difference, 1.2%; 95% confidence interval, -0.9 to 3.2).
Cell-free DNA screening test failures are relatively common. Although repeated testing improves the likelihood of an informative result, pregnancies with a failed cell-free DNA screen upon first attempt remain at increased risk for common autosomal aneuploidies, but not sex chromosome aneuploidies.
摘要：
背景：无细胞胎儿DNA筛查通常提供给妊娠个体以筛查非整倍体。虽然无细胞DNA筛选比多重标记筛选更准确，它有时无法产生结果。这些测试失败及其临床意义在文献中描述甚少。一些研究表明，失败的无细胞DNA筛选结果与细胞遗传学异常的可能性增加有关。
目的：我们研究的目的是评估无细胞DNA检测失败与常见非整倍体之间的关联。目标是确定：（1）在第一次和随后的尝试中测试失败的比例，（2）首次尝试失败的无细胞DNA筛选是否与常见非整倍体（21、18、13三体和性染色体非整倍体）的可能性增加有关。
方法：这是一项基于人群的回顾性队列研究，使用安大略省规定的母婴登记数据，更好的结果登记和网络（出生）安大略省。该研究包括安大略省的所有单胎妊娠，估计分娩日期为2016年9月1日至2019年3月31日，在注册表中具有无细胞DNA筛查记录。将首次尝试无细胞DNA筛选失败的妊娠的特定结果（三体21、18、13和性染色体非整倍体）与获得低风险无细胞DNA筛选结果的妊娠进行比较；使用针对资金状况（公共资助与自费）进行调整的改良泊松回归，筛查时的胎龄，受孕方法以及常染色体非整倍体的母体年龄。
结果：我们的队列包括在研究期间进行无细胞DNA筛查的35,146例妊娠。总的无细胞DNA筛选失败率在第一次尝试时为4.8%,在多次尝试后为2.2%。在19.4％的无细胞DNA筛查失败的妊娠中，发现了21、18、13三体或性染色体非整倍体的异常细胞遗传学结果，并进行了细胞遗传学测试。首次尝试无细胞DNA筛选失败的孕妇对21三体，18三体或13三体的相对风险为130.3（95CI：64.7，262.6），风险差异为5.4％（95CI：2.6，8.3）。与低风险结果的怀孕相比。与低风险结果的妊娠相比，失败的妊娠发生性染色体非整倍体的风险并未显着增加（相对风险2.7，95CI：0.9，7.9；相对差异1.2％，95CI：-0.9，3.2）。
结论：无细胞DNA筛选试验失败比较常见。虽然重复测试提高了信息结果的可能性，首次尝试无细胞DNA筛选失败的妊娠，常见常染色体非整倍体的风险仍然增加，但不是性染色体非整倍体。
目的：我们研究的目的是评估无细胞DNA检测失败与常见非整倍体之间的关联。目标是确定：（1）在第一次和随后的尝试中测试失败的比例，（2）首次尝试失败的无细胞DNA筛选是否与常见非整倍体（21、18、13三体和性染色体非整倍体）的可能性增加有关。
方法：这是一项基于人群的回顾性队列研究，使用安大略省规定的母婴登记数据，更好的结果登记和网络（出生）安大略省。该研究包括安大略省的所有单胎妊娠，估计分娩日期为2016年9月1日至2019年3月31日，在注册表中具有无细胞DNA筛查记录。将首次尝试无细胞DNA筛选失败的妊娠的特定结果（三体21、18、13和性染色体非整倍体）与获得低风险无细胞DNA筛选结果的妊娠进行比较；使用针对资金状况（公共资助与自费）进行调整的改良泊松回归，筛查时的胎龄，受孕方法以及常染色体非整倍体的母体年龄。
结果：我们的队列包括在研究期间进行无细胞DNA筛查的35,146例妊娠。总的无细胞DNA筛选失败率在第一次尝试时为4.8%,在多次尝试后为2.2%。在19.4％的无细胞DNA筛查失败的妊娠中，发现了21、18、13三体或性染色体非整倍体的异常细胞遗传学结果，并进行了细胞遗传学测试。首次尝试无细胞DNA筛选失败的孕妇对21三体，18三体或13三体的相对风险为130.3（95CI：64.7，262.6），风险差异为5.4％（95CI：2.6，8.3）。与低风险结果的怀孕相比。与低风险结果的妊娠相比，失败的妊娠发生性染色体非整倍体的风险并未显着增加（相对风险2.7，95CI：0.9，7.9；相对差异1.2％，95CI：-0.9，3.2）。
结论：无细胞DNA筛选试验失败比较常见。虽然重复测试提高了信息结果的可能性，首次尝试无细胞DNA筛选失败的妊娠，常见常染色体非整倍体的风险仍然增加，但不是性染色体非整倍体。
