Maternal-Fetal Medicine Unit, Maternal-Fetal Medicine Department, Hospital Universitari Vall d'Hebron, Ps. Vall d'Hebron 119-129, 08035, Barcelona, Spain.
Universitat Autònoma de Barcelona, Barcelona, Spain.
BMC Pregnancy Childbirth. 2019 Aug 1;19(1):274. doi: 10.1186/s12884-019-2434-0.
Different strategies have been designed for clinical implementation of cell-free DNA (cfDNA) testing. We aimed to evaluate the performance of a contingent strategy based on conventional screening and offering cfDNA to the intermediate-risk group, for the screening for trisomies 21, 18 and 13. Secondary objectives were to assess the uptake of cfDNA in women with intermediate-risk, to evaluate the performance of cfDNA testing, and the preferences of pregnant women with intermediate risk.
Prospective observational pilot study between February 2016 and March 2017. Singleton pregnancies with a known outcome were included in the study. At the conventional screening (first trimester combined test or second trimester quadruple test) women were classified in high (risk ≥1:250) or low risk (< 1:250). For the study, a contingent strategy was applied: following the conventional screening women were classified into three groups: high risk (risk ≥1:10 or nuchal translucency ≥3 mm), intermediate-risk (risk 1:11 to 1:1500) and low risk (< 1:1500), and a cfDNA test was offered to those at the intermediate risk.
For the analysis, 2639 women were included, 2422 (91.8%) had a first trimester combined test and 217 (8.2%) a second trimester quadruple test. There were 5 cases of trisomy 21, 4 of trisomy 18 and none of trisomy 13. For the contingent strategy, the detection rate and false positive rates were 88.9% (8/9) and 1.3% (35/2630), respectively. For the conventional strategy, the detection rate and false positive rates were 66.7% (6/9) and 5.3% (140/2630), respectively. The cfDNA test had a detection rate for trisomy 21 of 100% (3 out of 3), and a false positive rate of 0.2% (1/466). In a survey, 81.8% (374/457) of women in the intermediate-risk group would choose cfDNA testing as the second line test, mainly due to the lack of risk for the fetus.
A contingent screening strategy for trisomies 21, 18 and 13, based on conventional screening, and offering a cfDNA test to women with a risk between 1:11 to 1:1500, reduced the false positive rate and increased the detection rate for these trisomies. Moreover, this strategy is well accepted by women.
已经设计了不同的策略来将游离 DNA（cfDNA）检测应用于临床。我们旨在评估基于常规筛查并为中风险组提供 cfDNA 的条件策略，以筛查 21 三体、18 三体和 13 三体。次要目标是评估 cfDNA 在中风险女性中的应用，评估 cfDNA 检测的性能以及具有中风险的孕妇的偏好。
这是一项 2016 年 2 月至 2017 年 3 月之间进行的前瞻性观察性试点研究。本研究纳入了已知结局的单胎妊娠。在常规筛查（早孕期联合筛查或中孕期四联筛查）中，女性被分为高风险（风险≥1:250）或低风险（<1:250）。对于本研究，采用了条件策略：在常规筛查后，女性被分为三组：高风险（风险≥1:10 或颈项透明层≥3mm）、中风险（风险 1:11 至 1:1500）和低风险（<1:1500），并为中风险组提供 cfDNA 检测。
在分析中，共纳入 2639 名女性，其中 2422 名（91.8%）进行了早孕期联合筛查，217 名（8.2%）进行了中孕期四联筛查。有 5 例 21 三体，4 例 18 三体，没有 13 三体。对于条件策略，检出率和假阳性率分别为 88.9%（8/9）和 1.3%（35/2630）。对于常规策略，检出率和假阳性率分别为 66.7%（6/9）和 5.3%（140/2630）。cfDNA 检测对 21 三体的检出率为 100%（3/3），假阳性率为 0.2%（1/466）。在一项调查中，81.8%（374/457）的中风险组女性会选择 cfDNA 检测作为二线检测，主要是因为胎儿风险较低。
基于常规筛查，对 21 三体、18 三体和 13 三体采用条件筛查策略，并为风险在 1:11 至 1:1500 之间的女性提供 cfDNA 检测，可降低假阳性率并提高这些三体的检出率。此外，该策略得到了女性的认可。
