Prenatal Screening Ontario (Dougan, Okun, Bellai-Dussault, Meng, Huang, Reszel, Lanes, Walker, Armour), Better Outcomes Registry & Network (BORN) Ontario; Children's Hospital of Eastern Ontario (CHEO) Research Institute (Dougan, Bellai-Dussault, Howley, Reszel, Walker, Armour), Ottawa, Ont.; Mount Sinai Hospital (Okun); Genetics Program (Huang), North York General Hospital; Department of Obstetrics and Gynecology (Huang), University of Toronto, Toronto, Ont.; Department of Obstetrics and Gynecology (Walker), University of Ottawa; Ottawa Hospital Research Institute (OHRI) (Walker); Department of Pediatrics (Armour), University of Ottawa, Ottawa, Ont.
CMAJ. 2021 Aug 3;193(30):E1156-E1163. doi: 10.1503/cmaj.202456.
The emergence of cell-free fetal DNA (cfDNA) testing technology has disrupted the landscape of prenatal screening for trisomies 21 (T21) and 18 (T18). Publicly funded systems around the world are grappling with how to best integrate this more accurate but costly technology, as there is limited evidence about its incremental value in real-world conditions. The objectives of this study were to describe the population-based performance of Ontario's prenatal screening program, which incorporates publicly funded cfDNA screening for specific indications, and the effect of cfDNA testing on the screening and diagnostic choices made by pregnant people.
We conducted a retrospective, descriptive cohort study using routinely collected data from Better Outcomes & Registry Network (BORN) Ontario, which captures linked population data for prenatal and neonatal health encounters across Ontario. We included all singleton pregnancies with an estimated due date between Sept. 1, 2016, and Mar. 31, 2019, that underwent publicly funded prenatal screening in Ontario, and a comparison cohort from Apr. 1, 2012, and Mar. 31, 2013. We assessed performance of the screening program for the detection of T21 or T18 by calculating sensitivity, specificity, positive predictive value and negative predictive value against diagnostic cytogenetic results or birth outcomes. We assessed the impact of the program by calculating the proportion of T21 screen-positive pregnancies undergoing subsequent cfDNA screening and invasive prenatal diagnostic testing.
The study cohort included 373 682 pregnancies. The prenatal screening program had an uptake of 69.9%, a screen-positive rate and sensitivity of 1.6% and 89.9% for T21, and 0.2% and 80.5% for T18, respectively. The test failure rate for cfDNA screening was 2.2%. Invasive prenatal diagnostic testing decreased from 4.4% in 2012-2013 to 2.4% over the study period; 65.2% of pregnant people who received a screen-positive result from cfDNA testing went on to have invasive prenatal diagnostic testing.
This publicly funded screening program, incorporating cfDNA analysis for common aneuploidies, showed robust performance, a substantial reduction in invasive prenatal diagnostic testing and that pregnant people exercise autonomy in their choices about prenatal screening and diagnosis.
游离胎儿 DNA（cfDNA）检测技术的出现颠覆了 21 三体（T21）和 18 三体（T18）的产前筛查格局。世界各地的公共资助系统都在努力探索如何最好地整合这种更准确但成本更高的技术，因为关于其在实际条件下的增量价值的证据有限。本研究的目的是描述安大略省产前筛查计划的基于人群的表现，该计划纳入了针对特定指征的公共资助 cfDNA 筛查，以及 cfDNA 检测对孕妇筛查和诊断选择的影响。
我们进行了一项回顾性描述性队列研究，使用 Better Outcomes & Registry Network（BORN）安大略省的常规收集数据，该网络捕获了安大略省整个孕期和新生儿健康就诊的链接人群数据。我们纳入了所有在 2016 年 9 月 1 日至 2019 年 3 月 31 日期间在安大略省接受公共资助产前筛查的单胎妊娠，以及 2012 年 4 月 1 日至 2013 年 3 月 31 日的对照组。我们通过计算对诊断性细胞遗传学结果或出生结局的敏感性、特异性、阳性预测值和阴性预测值来评估筛查计划对 T21 或 T18 的检测性能。我们通过计算 T21 筛查阳性妊娠中随后进行 cfDNA 筛查和侵入性产前诊断检测的比例来评估该计划的影响。
研究队列包括 373682 例妊娠。产前筛查计划的接受率为 69.9%，T21 的筛查阳性率和敏感性分别为 1.6%和 89.9%，T18 的筛查阳性率和敏感性分别为 0.2%和 80.5%。cfDNA 筛查的检测失败率为 2.2%。2012-2013 年，侵入性产前诊断检测的比例为 4.4%，而在研究期间降至 2.4%；65.2%接受 cfDNA 筛查阳性结果的孕妇进行了侵入性产前诊断检测。
该公共资助的筛查计划纳入了常见非整倍体的 cfDNA 分析，显示出良好的性能、显著减少了侵入性产前诊断检测，并且孕妇在产前筛查和诊断方面行使自主权。
