Department of Women's Health, University Hospital Tuebingen, Tuebingen, Germany.
Department of Neonatology, University Hospital Tuebingen, Tuebingen, Germany.
Fetal Diagn Ther. 2022;49(3):85-94. doi: 10.1159/000523738. Epub 2022 Feb 22.
The aim of the objective was to compare the detection rate for trisomy 21 of universal cell free DNA (cfDNA) screening with contingent screening.
Retrospective study was carried out at 3 German centers. The study included euploid and trisomy 21 pregnancies where cfDNA and first trimester (FT) screening assessment was carried out. The FT risk for trisomy 21 was computed based on combined screening and stratified into the following classes: high risk ≥1:10, intermediate risk 1:11-1,000, low risk ≤1,001. For universal cfDNA screening, the cfDNA test results were examined. For the contingent screening model, the result of the cfDNA test was taken into account in case of an intermediate FT risk. Different strategies combining maternal age, nuchal translucency, nasal bone, beta-hCG, and PAPP-A were evaluated. Screen positivity was defined as either a high risk after FT screening or a cfDNA test indicating a high-risk result. An inconclusive cfDNA test was also considered as screen positive.
The search of the database identified 2,255 euploid and 163 affected pregnancies. All affected fetuses were identified by universal cfDNA screening. 1.3% of the euploid fetuses were classified as screen positive due to final inconclusive cfDNA test result. The detection and false-positive rate of a contingent approach that is based on combined screening and cfDNA screening in the intermediate group would be 98.4% and 0.7%, respectively. With this approach, cfDNA screening would be necessary in only about 27% of all pregnancies.
This study demonstrates that a contingent approach provides similar detection rates for trisomy 21 as universal cfDNA screening, by a reduction of 73% the number of cfDNA tests.
本研究旨在比较全基因组游离 DNA（cfDNA）筛查与有条件筛查对 21 三体的检出率。
本研究在德国的 3 个中心进行了回顾性研究。研究纳入了染色体正常和 21 三体的妊娠，对 cfDNA 和早孕期（FT）筛查进行了评估。根据联合筛查将 FT 21 三体风险计算为以下风险类别：高风险≥1:10，中风险 1:11-1000，低风险≤1001。对于全基因组 cfDNA 筛查，检查 cfDNA 检测结果。对于有条件筛查模型，仅在 FT 风险为中风险时考虑 cfDNA 检测结果。评估了不同的策略，这些策略将母亲年龄、颈项透明层、鼻骨、β-hCG 和 PAPP-A 结合在一起。将阳性筛查定义为 FT 筛查后的高风险或 cfDNA 检测提示高风险结果。也将不确定的 cfDNA 检测结果视为阳性筛查。
数据库搜索鉴定了 2255 例染色体正常和 163 例受累妊娠。所有受累胎儿均通过全基因组 cfDNA 筛查鉴定。由于最终不确定的 cfDNA 检测结果，1.3%的染色体正常胎儿被归类为阳性筛查。基于联合筛查和 cfDNA 筛查的中间组的有条件方法的检出率和假阳性率分别为 98.4%和 0.7%。采用这种方法，仅在约 27%的所有妊娠中需要进行 cfDNA 筛查。
本研究表明，与全基因组 cfDNA 筛查相比，有条件方法通过减少 73%的 cfDNA 检测次数，提供了类似的 21 三体检出率。
