Cope Heidi L, Jalazo Elizabeth R, Berg Jonathan S, Sullivan Jennifer A, Kucera Katerina S, Shone Scott M, Frawley Hannah E, Gwaltney Angela Y, Forsythe Ana N, Migliore Brooke A, Wright Becca, Moultrie Rebecca R, Milko Laura V, Zimmerman Rebekah S, Kruszka Paul, Suchy Sharon F, Begtrup Amber, Langley Katherine G, Monaghan Kristin G, Kraczkowski Christina, Guenzel Adam J, McWalter Kirsty, Hruska Kathleen S, Bailey Donald B, Wheeler Anne C, Raspa Melissa, Powell Cynthia M, Peay Holly L
GenOmics and Translational Research Center, RTI International, Research Triangle Park, NC, USA.
Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Nat Med. 2025 Sep 5. doi: 10.1038/s41591-025-03945-8.
Although genomic sequencing presents groundbreaking newborn screening (NBS) opportunities, critical feasibility and utility questions remain. Here we present initial results from the Early Check program-an observational study assessing the feasibility and clinical utility of genomic NBS in North Carolina. Recruitment was statewide through mailed letters with electronic consent. Genome sequencing with analysis of 169 high actionability genes (plus 29 optional lower actionability genes) was performed using residual NBS dried blood spots. In 8 months, 1,979 newborns were screened, with 50 (2.5%) screen positives. Negative results were returned electronically, positive results by genetic counselors. Twenty-eight results (55%) were true positives, all received anticipatory guidance, surveillance and management recommendations, and referral to specialists as appropriate. We report technical feasibility and preliminary clinical utility finding, along with interpretation and follow-up challenges that hinder public health implementation. We propose standardized terminology to facilitate cross-study comparisons and accurate characterization of genomic NBS outcomes.
尽管基因组测序为新生儿筛查（NBS）带来了开创性的机遇，但关键的可行性和实用性问题依然存在。在此，我们展示了早期检查项目的初步结果——一项评估北卡罗来纳州基因组新生儿筛查的可行性和临床实用性的观察性研究。通过邮寄带有电子同意书的信件在全州范围内招募对象。利用新生儿筛查残留干血斑对169个高可操作性基因（外加29个可选的低可操作性基因）进行基因组测序及分析。在8个月内，对1979名新生儿进行了筛查，其中50名（2.5%）筛查呈阳性。阴性结果通过电子方式返回，阳性结果由遗传咨询师告知。28个结果（55%）为真阳性，所有这些结果均得到了预期指导、监测和管理建议，并在适当时转诊至专科医生处。我们报告了技术可行性和初步临床实用性结果，以及阻碍公共卫生实施的解读和随访挑战。我们提出标准化术语，以促进跨研究比较和对基因组新生儿筛查结果的准确描述。
