Department of Obstetrics and Gynecology, Salamanca University Hospital, Salamanca, Spain.
Department of Diagnostic and Biolomedical Sciences, Faculty of Medicine, Salamanca University, Salamanca, Spain.
Fetal Diagn Ther. 2022;49(3):103-113. doi: 10.1159/000523848. Epub 2022 Mar 8.
Universal screening for trisomy using cell-free DNA (cfDNA) has proven to be more effective than combined test, but it is not cost efficient currently. Contingent cfDNA screening on the results of the first-trimester combined test can improve the detection rate of the combined test and reduce the number of invasive tests at a lower cost than universal screening. In 2018, a contingent screening program was implemented in the community of Castilla y Leon (Spain). This study aims to compare the results achieved in Salamanca University Hospital during the first 3 years of contingent screening (2018-2020) with those of the previous 3 years (2015-2017) to assess the changes in the trisomy detection rate and the number of invasive tests.
A total of 9,903 singleton pregnancies without malformations nor nuchal translucency >p99 were included. 5,165 patients underwent combined screening and 4,738 had contingent screening based on the combined test risk. In the combined test group, women were offered an invasive test if the risk was ≥1:270, while risks under 1:270 were considered low risks, and no further testing was offered. In the contingent screening group, invasive testing was offered if the risk was ≥1:100 (≥1:50 from 2020 onwards), while cfDNA was offered if the combined test risk was between 1:100 and 1:1,000 (1:50-1:1,000 from 2020 onwards). When risk was <1:1,000, no further testing was offered. Aneuploidies detected by cfDNA were confirmed by invasive diagnostic testing.
There were 33 cases of trisomy 21 (T21) throughout the 6 years of study. Four cases had low/intermediate risks and were spotted by cfDNA. Risk >1:1,000 threshold for contingent test detected 100% T21. There was a false-positive result for trisomy 13. There were no false-negative results. "No-call" cfDNA results were minimized by repeating blood collection 2 weeks later, as fetal fraction (FF) was doubled. Invasive testing had a drop rate of 84% after contingent screening implementation.
The implementation of population-based contingent screening significantly reduces the number of invasive tests without lowering diagnostic accuracy. To achieve the maximum efficiency of the program, it is important to know the best cut-offs according to the population where the program is to be implemented. The number of uninformative results due to low FF can be reduced by repeating the test 2 weeks after the initial extraction: this increases the FF to twice the initial one, achieving informative results and avoiding unnecessary invasive tests.
使用游离胎儿 DNA（cfDNA）进行三体综合征的全基因组筛查已被证明比联合检测更有效，但目前其成本效益并不高。基于第一孕期联合检测结果的 cfDNA contingent 筛查可以提高联合检测的检出率，并以较低的成本降低侵袭性检测的数量，优于全基因组筛查。2018 年，在卡斯蒂利亚-莱昂（西班牙）社区实施了 contingent 筛查项目。本研究旨在比较在 contingent 筛查实施的前 3 年（2018-2020 年）在萨拉曼卡大学医院获得的结果与前 3 年（2015-2017 年）的结果，以评估三体综合征的检出率和侵袭性检测数量的变化。
共纳入 9903 例无畸形和颈项透明层厚度>p99 的单胎妊娠。5165 例患者接受了联合筛查，4738 例患者根据联合检测风险进行了 contingent 筛查。在联合检测组中，如果风险≥1:270，则为患者提供侵袭性检测，而风险<1:270 被认为是低风险，不提供进一步的检测。在 contingent 筛查组中，如果风险≥1:100（2020 年起≥1:50），则提供侵袭性检测，如果联合检测风险在 1:100 至 1:1000 之间（2020 年起 1:50-1:1000），则提供 cfDNA。如果风险<1:1000，则不提供进一步的检测。cfDNA 检测到的非整倍体通过侵袭性诊断检测得到确认。
6 年研究期间共发现 33 例 21 三体综合征（T21）。4 例为低/中风险，通过 cfDNA 发现。 contingent 检测的风险>1:1000 阈值检测到 100%的 T21。出现 13 三体假阳性结果。没有假阴性结果。通过在初始采集后 2 周重复采血，使胎儿分数（FF）加倍，最小化了“无结果”的 cfDNA 结果。 contingent 筛查实施后，侵袭性检测的下降率为 84%。
基于人群的 contingent 筛查的实施显著降低了侵袭性检测的数量，而不会降低诊断准确性。为了实现该计划的最大效率，根据将要实施该计划的人群确定最佳截止值非常重要。通过在初始提取后 2 周重复检测，可以减少因低 FF 导致的无信息结果数量：这将 FF 增加到初始值的两倍，获得信息结果，并避免不必要的侵袭性检测。
