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扩展携带者筛查用于生殖风险评估:来自国家遗传咨询师协会的循证实践指南。

Expanded carrier screening for reproductive risk assessment: An evidence-based practice guideline from the National Society of Genetic Counselors.

机构信息

Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Write InSciTe, LLC, South Salem, New York, USA.

出版信息

J Genet Couns. 2023 Jun;32(3):540-557. doi: 10.1002/jgc4.1676. Epub 2023 Feb 9.

Abstract

Expanded carrier screening (ECS) intends to broadly screen healthy individuals to determine their reproductive chance for autosomal recessive (AR) and X-linked (XL) conditions with infantile or early-childhood onset, which may impact reproductive management (Committee Opinion 690, Obstetrics and Gynecology, 2017, 129, e35). Compared to ethnicity-based screening, which requires accurate knowledge of ancestry for optimal test selection and appropriate risk assessment, ECS panels consist of tens to hundreds of AR and XL conditions that may be individually rare in various ancestries but offer a comprehensive approach to inherited disease screening. As such, the term "equitable carrier screening" may be preferable. This practice guideline provides evidence-based recommendations for ECS using the GRADE Evidence to Decision framework (Guyatt et al., BMJ, 2008, 336, 995; Guyatt et al., BMJ, 2008, 336, 924). We used evidence from a recent systematic evidence review (Ramdaney et al., Genetics in Medicine, 2022, 20, 374) and compiled data from peer-reviewed literature, scientific meetings, and clinical experience. We defined and prioritized the outcomes of informed consent, change in reproductive plans, yield in identification of at-risk carrier pairs/pregnancies, perceived barriers to ECS, amount of provider time spent, healthcare costs, frequency of severely/profoundly affected offspring, incidental findings, uncertain findings, patient satisfaction, and provider attitudes. Despite the recognized barriers to implementation and change in management strategies, this analysis supported implementation of ECS for these outcomes. Based upon the current level of evidence, we recommend ECS be made available for all individuals considering reproduction and all pregnant reproductive pairs, as ECS presents an ethnicity-based carrier screening alternative which does not rely on race-based medicine. The final decision to pursue carrier screening should be directed by shared decision-making, which takes into account specific features of patients as well as their preferences and values. As a periconceptional reproductive risk assessment tool, ECS is superior compared to ethnicity-based carrier screening in that it both identifies more carriers of AR and XL conditions as well as eliminates a single race-based medical practice. ECS should be offered to all who are currently pregnant, considering pregnancy, or might otherwise biologically contribute to pregnancy. Barriers to the broad implementation of and access to ECS should be identified and addressed so that test performance for carrier screening will not depend on social constructs such as race.

摘要

扩展携带者筛查 (ECS) 旨在广泛筛查健康个体,以确定其具有婴儿期或幼儿期发病的常染色体隐性 (AR) 和 X 连锁 (XL) 疾病的生殖机会,这可能会影响生殖管理 (委员会意见 690,妇产科,2017 年,129,e35)。与基于种族的筛查相比,后者需要准确了解种族以进行最佳测试选择和适当的风险评估,ECS 面板包含数十到数百种 AR 和 XL 疾病,这些疾病在不同的种族中可能单独很少见,但提供了一种综合的遗传疾病筛查方法。因此,“公平携带者筛查”这一术语可能更合适。本实践指南使用 GRADE 证据决策框架 (Guyatt 等人,BMJ,2008 年,336,995;Guyatt 等人,BMJ,2008 年,336,924) 为 ECS 提供了基于证据的建议。我们使用了最近系统证据综述 (Ramdaney 等人,《遗传医学》,2022 年,20,374) 的证据,并汇编了同行评议文献、科学会议和临床经验的数据。我们定义并优先考虑知情同意的结果、生殖计划的改变、识别高危携带者对/妊娠的结果、ECS 的感知障碍、提供者花费的时间量、医疗保健成本、严重/重度受影响后代的频率、偶然发现、不确定发现、患者满意度和提供者态度。尽管实施和改变管理策略存在公认的障碍,但该分析支持对这些结果进行 ECS。基于当前证据水平,我们建议为所有考虑生育的个体和所有有生育能力的妊娠对提供 ECS,因为 ECS 提供了一种基于种族的携带者筛查替代方案,而不依赖于基于种族的医学。进行携带者筛查的最终决定应由共同决策指导,共同决策既要考虑患者的具体特征,也要考虑他们的偏好和价值观。作为一种围孕期生殖风险评估工具,与基于种族的携带者筛查相比,ECS 具有优势,因为它既能识别更多的 AR 和 XL 疾病携带者,又能消除单一的基于种族的医疗实践。应向所有目前怀孕、考虑怀孕或可能以其他方式对怀孕有生物学贡献的人提供 ECS。应确定和解决 ECS 广泛实施和获得的障碍,以便携带者筛查的测试性能不会依赖于种族等社会结构。

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