Genetics Program, North York General Hospital, 4001 Leslie Street, Toronto, Ontario, M2K 1E1, Canada.
Prenatal Screening Ontario, Better Outcomes Registry & Network (BORN) Ontario, Ottawa, Ontario, Canada.
BMC Pregnancy Childbirth. 2020 Nov 23;20(1):713. doi: 10.1186/s12884-020-03394-w.
Prenatal screening for chromosome aneuploidies have constantly been evolving, especially with the introduction of cell-free fetal DNA (cfDNA) screening in the most recent years. This study compares the performance, costs and timing of test results of three cfDNA screening implementation strategies: contingent, reflex and primary.
We modelled enhanced first trimester screening (eFTS) as the first-tier test in contingent or reflex strategies. cfDNA test was performed contingent on or reflex from eFTS results. A comparison was made between cfDNA screening using sequencing technology and Rolling Circle Amplification (RCA)/imaging solution. All model assumptions were based on results from previous publications or information from the Ontario prenatal screening population.
At an eFTS risk cut-off of ≥1/1000, contingent and reflex cfDNA screening have the same detection rate (DR) (94%) for trisomy 21. Reflex cfDNA screening using RCA/Imaging solution provided the lowest false positive rate and cost. The number of women requiring genetic counselling and diagnostic testing was significantly reduced and women received their cfDNA screening result 9 days sooner compared with the contingent model. While primary cfDNA screening improved the trisomy 21 DR by 3-5%, it was more costly and more women required diagnostic testing.
Reflex cfDNA screening is the most cost-effective prenatal screening strategy. It can improve the efficiency of prenatal aneuploidy screening by reducing the number of patient visits and providing more timely results.
染色体非整倍体的产前筛查一直在不断发展，尤其是近年来引入了游离胎儿 DNA（cfDNA）筛查。本研究比较了三种 cfDNA 筛查实施策略的性能、成本和检测结果时间：有条件的、反射的和主要的。
我们将增强型早期筛查（eFTS）作为有条件或反射策略的一线检测。cfDNA 检测根据 eFTS 结果进行有条件或反射。比较了使用测序技术和滚环扩增（RCA）/成像解决方案的 cfDNA 筛查。所有模型假设均基于之前的出版物结果或安大略省产前筛查人群的信息。
在 eFTS 风险截止值≥1/1000 时，有条件和反射 cfDNA 筛查对 21 三体的检测率（DR）相同（94%）。使用 RCA/成像解决方案的反射 cfDNA 筛查提供了最低的假阳性率和成本。需要遗传咨询和诊断测试的妇女人数显著减少，与有条件模型相比，妇女更早获得 cfDNA 筛查结果（提前 9 天）。虽然主要的 cfDNA 筛查提高了 21 三体的 DR 3-5%，但它的成本更高，需要更多的妇女进行诊断测试。
反射 cfDNA 筛查是最具成本效益的产前筛查策略。它可以通过减少患者就诊次数和提供更及时的结果来提高产前非整倍体筛查的效率。
