Elucidating the barriers and facilitators to widespread implementation of preconception genetic carrier screening

筛选未来的父母，以确定他们的后代是否有潜在的破坏性遗传风险， 遗传携带者筛查导致新生儿数量明显减少， 患有严重的隐性遗传疾病虽然专业协会，如美国大学， 妇产科医生和美国医学遗传学学会提倡遗传携带者 在怀孕前进行筛查（孕前），接受孕前遗传携带者筛查 仍然很低，不公平。这是因为在不同的国家实施携带者筛查 人口是复杂的，需要1）了解在所有级别的筛查的障碍和促进因素， 医疗保健递送，2）识别患者对测试递送的偏好，以及3）澄清潜在的个人偏好。 携带者筛查对健康的影响。该奖项将用于解决这三个差距， 了解孕前遗传携带者筛查。首先，我会采访有经验的关键线人 在各级医疗保健服务，他们对实施的障碍和促进因素的看法 孕前携带者筛查项目第二，我将系统地引出患者的偏好， 遗传携带者筛查应使用离散选择实验进行。离散选择 实验将包括一个基于网络的调查，其中不同的属性如何前概念载体 提供的筛查是多种多样的，潜在的患者必须选择他们喜欢的筛查方法。这 将对两组不同的育龄妇女进行调查， 应答最后，我将使用全表型关联研究方法，调查是否携带者 常染色体隐性遗传疾病是其他成人疾病的高风险。我将专注于CFTR、HBB和GBA， 与常染色体隐性遗传疾病囊性纤维化、镰状细胞性贫血和戈谢病有关 疾病，分别。这项研究将产生关键的试点数据，将用于设计可测试的实施 使孕前携带者筛查能够广泛使用的战略。这些战略及其对 病人护理随后将通过未来的拨款申请在随机临床试验中进行测试。

Screening of prospective parents to determine if their offspring are at risk for potentially devastating heritable conditions with genetic carrier screening has resulted in measurable decreases in the number of newborns affected by severe recessive disorders. Although professional societies such as the American College of Obstetricians and Gynecologists and the American College of Medical Genetics advocate for genetic carrier screening to be done prior to pregnancy (preconception), access to preconception genetic carrier screening remains low and inequitable. This is because implementation of carrier screening in a diverse national population is complicated and requires 1) understanding the barriers and facilitators of screening at all levels of healthcare delivery, 2) recognizing patient preferences for test delivery, and 3) clarifying potential personal health implications of carrier screening. This award will be used to address these three gaps in our understanding of preconception genetic carrier screening. First, I will interview key informants with experience at all levels of healthcare delivery about their perceptions of the barriers and facilitators to implementing preconception carrier screening programs. Second, I will systematically elicit patient preferences about how genetic carrier screening should be delivered using a discrete choice experiment. The discrete choice experiment will consist of a web-based survey in which different attributes of how preconception carrier screening is offered are varied and prospective patients must choose their preferred screening method. This survey will be administered to two separate cohorts of women of reproductive age to encourage a diversity of responses. Finally, I will use phenome-wide association study methods to investigate whether carriers of autosomal recessive disease are at high risk of other adult diseases. I will focus on CFTR, HBB, and GBA, which are implicated in the autosomal recessive disorders cystic fibrosis, sickle cell anemia, and Gaucher disease, respectively. This study will generate key pilot data that will be used to design testable implementation strategies to enable widespread use of preconception carrier screening. These strategies and their impact on patient care will subsequently be tested in a randomized clinical trial through a future grant application.