Efforts to implement and evaluate genome sequencing (GS) as a screening tool for newborns and infants are expanding worldwide. The first iteration of the BabySeq Project (2015–2019), a randomized controlled trial of newborn sequencing, produced novel evidence on medical, behavioral, and economic outcomes. The second iteration of BabySeq, which began participant recruitment in January 2023, examines GS outcomes in a larger, more diverse cohort of more than 500 infants up to one year of age recruited from pediatric clinics at several sites across the United States. The trial aims for families who self-identify as Black/African American or Hispanic/Latino to make up more than 50% of final enrollment, and key aspects of the trial design were co-developed with a community advisory board. All enrolled families receive genetic counseling and a family history report. Half of enrolled infants are randomized to receive GS with comprehensive interpretation of pathogenic and likely pathogenic variants in more than 4,300 genes associated with childhood-onset and actionable adult-onset conditions, as well as larger-scale chromosomal copy number variants classified as pathogenic or likely pathogenic. GS result reports include variants associated with disease (Mendelian disease risks) and carrier status of autosomal-recessive and X-linked disorders. Investigators evaluate the utility and impacts of implementing a GS screening program in a diverse cohort of infants using medical record review and longitudinal parent surveys. In this perspective, we describe the rationale for the second iteration of the BabySeq Project, the outcomes being assessed, and the key decisions collaboratively made by the study team and community advisory board.

中文翻译：

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BabySeq 项目：对不同婴儿队列进行基因组测序的临床试验


实施和评估基因组测序 （GS） 作为新生儿和婴儿筛查工具的努力正在世界范围内扩大。BabySeq 项目的第一代 （2015-2019） 是一项新生儿测序的随机对照试验，在医学、行为和经济结果方面产生了新的证据。BabySeq 的第二次迭代于 2023 年 1 月开始招募参与者，检查了从美国多个地点的儿科诊所招募的 500 多名更大、更多样化的 1 岁以下婴儿的 GS 结果。该试验旨在使自我认同为黑人/非裔美国人或西班牙裔/拉丁裔的家庭占最终入组人数的 50% 以上，试验设计的关键方面是与社区咨询委员会共同制定的。所有登记的家庭都会接受遗传咨询和家族史报告。一半的入组婴儿被随机分配接受 GS，全面解释 4,300 多个与儿童期发病和可操作的成人发病情况相关的基因中的致病性和可能的致病性变异，以及归类为致病性或可能致病性的更大规模染色体拷贝数变异。GS 结果报告包括与疾病相关的变异（孟德尔病风险）和常染色体隐性遗传病和 X 连锁疾病的携带者状态。研究人员使用病历审查和纵向父母调查评估在不同的婴儿队列中实施 GS 筛查计划的效用和影响。从这个角度来看，我们描述了 BabySeq 项目第二次迭代的基本原理、正在评估的结果以及研究团队和社区咨询委员会共同做出的关键决策。