Huang Tianhua, Meschino Wendy S, Teitelbaum Mari, Dougan Shelley, Okun Nan
Genetics Program, North York General Hospital, Toronto, ON; Better Outcomes Registry & Network (BORN) Ontario, Ottawa, ON; The Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON.
Genetics Program, North York General Hospital, Toronto, ON; Department of Paediatrics, University of Toronto, Toronto, ON.
J Obstet Gynaecol Can. 2017 Sep;39(9):742-749. doi: 10.1016/j.jogc.2017.01.025. Epub 2017 Jun 16.
Prenatal screening for trisomy 21 is a standard of care. Emerging cell-free fetal DNA (cffDNA) technologies can improve screening performance, but they are expensive. This study was conducted to propose a contingent screening model that would incorporate cffDNA technology, would remain affordable, and could be applied equitably in a publically funded system.
Using performance and cost parameters from published literature, four prenatal screening strategies were compared. Scenario 1 modelled integrated prenatal screening (first trimester nuchal translucency and biochemical markers from both the first and second trimesters) with no cffDNA. Scenarios 2 and 3 modelled first trimester combined screening (FTS) and "enhanced FTS" (adding serum placental growth factor and alpha fetoprotein to FTS), respectively, with contingent cffDNA following a positive result. Scenario 4 modelled cffDNA as the primary screening test.
Scenario 1 provides a known detection rate (DR) of 88%, with a false positive rate (FPR) of 3.3%. Scenarios 2 and 3 result in a DR of 94% and overall FPR of 0.59% and 0.33%, respectively, comparable to the DR of 96% and FPR of 0.1% with primary cffDNA (assuming the published test failure rate of 3%). The total cost, cost per woman screened, and cost per case of trisomy 21 detected were lower with scenario 3 (enhanced FTS with contingent cffDNA) compared with primary cffDNA or scenario 2 (FTS with contingent cffDNA).
Enhanced FTS with contingent cffDNA following a positive result provides a similar performance to that of primary cffDNA at a substantially lower cost.
对21三体综合征进行产前筛查是一种标准医疗服务。新兴的游离胎儿DNA（cffDNA）技术可提高筛查效能，但成本高昂。本研究旨在提出一种可能的筛查模式，该模式纳入cffDNA技术后仍可负担得起，并能在公共资助体系中公平应用。
利用已发表文献中的效能和成本参数，对四种产前筛查策略进行比较。方案1模拟了不使用cffDNA的综合产前筛查（孕早期颈部透明带厚度以及孕早期和孕中期的生化标志物）。方案2和方案3分别模拟了孕早期联合筛查（FTS）和“强化FTS”（在FTS基础上增加血清胎盘生长因子和甲胎蛋白），检测结果为阳性后追加cffDNA检测。方案4模拟将cffDNA作为主要筛查检测方法。
方案1的已知检测率（DR）为88%，假阳性率（FPR）为3.3%。方案2和方案3的DR分别为94%，总体FPR分别为0.59%和0.33%，与将cffDNA作为主要检测方法时的DR 96%和FPR 0.1%相当（假设已发表的检测失败率为3%）。与将cffDNA作为主要检测方法或方案2（检测结果为阳性后进行FTS并追加cffDNA检测）相比，方案3（检测结果为阳性后进行强化FTS并追加cffDNA检测）的总成本、每位接受筛查女性的成本以及每例检测出的21三体综合征病例的成本更低。
检测结果为阳性后进行强化FTS并追加cffDNA检测，其效能与将cffDNA作为主要检测方法相近，但成本大幅降低。
