Kaimal Anjali J, Norton Mary E, Kuppermann Miriam
Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, Massachusetts; and the Departments of Obstetrics, Gynecology & Reproductive Sciences and Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, California.
Obstet Gynecol. 2015 Oct;126(4):737-746. doi: 10.1097/AOG.0000000000001029.
To use a decision-analytic model to assess a comprehensive set of outcomes of prenatal genetic testing strategies among women of varying ages.
We assessed outcomes of six testing strategies incorporating diagnostic testing with chromosomal microarray, multiple marker screening, cell-free DNA screening, and nuchal translucency screening alone, in combination, or in sequence. Clinical outcomes included prenatal detection or birth of a neonate with a significant chromosomal abnormality and diagnostic procedures performed. Other outcomes included maternal quality-adjusted life-years and costs. Sensitivity analyses were conducted to examine the robustness of the findings.
At all ages assessed, screening strategies starting with multiple marker screening offered the highest detection rate when all chromosomal abnormalities were considered. Incorporating cell-free DNA as an optional secondary screen decreased the number of diagnostic procedures, but also decreased the number of abnormalities diagnosed prenatally, resulting in a similar number of procedures per case diagnosed at age 30 years; the option of secondary cell-free DNA screening becomes more favorable at older ages. Multiple marker screening with optional follow-up diagnostic testing was the most effective (highest quality-adjusted life-years) and least expensive strategy at ages 20-38 years. At age 40 years or older, cell-free DNA screening was optimal with an incremental cost-effectiveness ratio of $73,154 per quality-adjusted life-year.
When considering all detectable chromosome problems as well as patient preferences and baseline risks, multiple marker screening with the option of diagnostic testing for screen-positive results is the optimal strategy for most women. At age 40 years and older, cell-free DNA as a primary screen becomes optimal and is cost-effective.
II.
使用决策分析模型评估不同年龄女性产前基因检测策略的一系列综合结果。
我们评估了六种检测策略的结果，这些策略包括单独、联合或按顺序使用染色体微阵列诊断检测、多项标志物筛查、游离DNA筛查和颈部透明带筛查。临床结果包括产前检测出或出生时患有重大染色体异常的新生儿以及所进行的诊断程序。其他结果包括孕产妇质量调整生命年和成本。进行敏感性分析以检验研究结果的稳健性。
在所有评估年龄中，当考虑所有染色体异常时，从多项标志物筛查开始的筛查策略检测率最高。将游离DNA作为可选的二次筛查可减少诊断程序的数量，但也会减少产前诊断出的异常数量，导致30岁时每例确诊病例的程序数量相似；二次游离DNA筛查选项在年龄较大时更有利。在20至38岁时，多项标志物筛查加可选的后续诊断检测是最有效的（质量调整生命年最高）且成本最低的策略。在40岁及以上，游离DNA筛查是最优的，每质量调整生命年的增量成本效益比为73,154美元。
在考虑所有可检测到的染色体问题以及患者偏好和基线风险时，多项标志物筛查加对筛查阳性结果进行诊断检测的选项是大多数女性的最佳策略。在40岁及以上，将游离DNA作为初次筛查是最优的且具有成本效益。
II级。
