Avram Carmen M, Shaffer Brian L, Sparks Teresa N, Allen Allison J, Caughey Aaron B
Department of Obstetrics and Gynecology, Oregon Health & Sciences University, Portland, OR, USA.
Department of Obstetrics, Gynecology, and Reproductive Sciences, Univeristy of California San Francisco, San Francisco, CA, USA.
J Matern Fetal Neonatal Med. 2021 Jun;34(11):1732-1740. doi: 10.1080/14767058.2019.1647161. Epub 2019 Aug 5.
Fetuses with genetic copy number variants are poorly detected through traditional prenatal screening. Microdeletions and duplications are clearly identified with diagnostic testing through chromosomal microarray, and screening of a select number of microdeletions has become available with cell-free DNA (cfDNA). Our study compares the costs and outcomes of cfDNA for five pathogenic microdeletions and aneuploidy to cfDNA for aneuploidy alone in conjunction with ultrasound.
A decision-analytic model was constructed using TreeAge software to compare cfDNA with microdeletions versus traditional cfDNA in a theoretical cohort of 4,000,000 pregnancies that would also be screened with ultrasound. Probabilities, costs, and utilities were derived from literature. The primary outcomes were the incremental cost per quality-adjusted life-year (QALY), terminations, and procedure-related losses. Because the microdeletion results are available, but not reported, on all cfDNA testing we set the incremental cost of the cfDNA microdeletion screening test to zero at baseline and varied the cost in sensitivity analysis.
Screening with cfDNA for microdeletions among all pregnant women would result in 83 fewer anomalous neonates compared to traditional cfDNA with ultrasound. This reduction is due to increased diagnosis and termination of fetuses with microdeletions in this group. Routine use of cfDNA with microdeletions resulted in more procedure-related losses. cfDNA with microdeletions would improve effectiveness by 977 QALYs and decrease costs by $90,991,784. When we varied the specificity of the screening test, we found that it remained cost-effective down to a specificity of 91%. With a threshold of $100,000/QALY, microdeletion screening is cost-effective to an incremental increase in cost over cfDNA for aneuploidy alone of $47.10.
For detection of fetal subchromosomal abnormalities, use of cfDNA with microdeletions is a cost-effective strategy compared to cfDNA for aneuploidy alone in conjunction with ultrasound. Cell-free DNA for microdeletions is not currently recommended as routine screening for low-risk obstetric populations by the American College of Obstetrics and Gynecologists or the Society for Maternal-Fetal Medicine. The test characteristics of cfDNA with microdeletions require greater examination before being routinely recommended.
通过传统产前筛查很难检测出具有基因拷贝数变异的胎儿。通过染色体微阵列进行诊断性检测能够明确识别微缺失和微重复，并且利用游离DNA（cfDNA）已可以对某些微缺失进行筛查。我们的研究比较了针对五种致病性微缺失和非整倍体的cfDNA与仅针对非整倍体并结合超声检查的cfDNA的成本和结果。
使用TreeAge软件构建一个决策分析模型，在一个理论上有400万例妊娠且也会接受超声检查的队列中，比较含有微缺失的cfDNA与传统cfDNA。概率、成本和效用均来自文献。主要结果是每质量调整生命年（QALY）的增量成本、终止妊娠情况以及与操作相关的损失。由于所有cfDNA检测均可获得微缺失结果但未报告，我们将cfDNA微缺失筛查检测的增量成本在基线时设为零，并在敏感性分析中改变成本。
与采用超声检查的传统cfDNA相比，对所有孕妇进行含微缺失的cfDNA筛查可减少83例异常新生儿。这种减少是由于该组中微缺失胎儿的诊断和终止妊娠增加。常规使用含微缺失的cfDNA会导致更多与操作相关的损失。含微缺失的cfDNA将使有效性提高977个QALY，并使成本降低90,991,784美元。当我们改变筛查检测的特异性时，发现其在特异性低至91%时仍具有成本效益。以100,000美元/QALY为阈值，微缺失筛查在相对于仅针对非整倍体的cfDNA成本增量增加47.10美元时具有成本效益。
对于检测胎儿亚染色体异常，与仅针对非整倍体并结合超声检查的cfDNA相比，使用含微缺失的cfDNA是一种具有成本效益的策略。美国妇产科学会和母胎医学会目前不建议将用于微缺失检测的游离DNA作为低风险产科人群的常规筛查方法。在被常规推荐之前，含微缺失cfDNA的检测特性需要进行更深入的研究。
