Feasibility and clinical utility of expanded genomic newborn screening in the Early Check program

作者：Heidi Cope, Elizabeth Jalazo, Jonathan S. Berg, Jennifer A. Sullivan, Katerina S. Kucera, Scott M. Shone, Hannah E. Frawley, Angela You Gwaltney, Ana Forsythe, Brooke Migliore, Becca Wright, Rebecca Moultrie, Laura V. Milko, Rebekah Zimmerman, Paul S. Kruszka, Sharon F. Suchy, Amber Hogart Begtrup, Katherine G. Langley, Kristin G. Monaghan, Christina Kraczkowski, Adam J. Guenzel, Kirsty M. McWalter, Kathleen S. Hruska, Donald B. Bailey, Anne Wheeler, Melissa Raspa, Cynthia M. Powell, Holly Landrum Peay, Early Check Program · 发表于：Nature Medicine · 年份：2025 · DOI：10.1038/s41591-025-03945-8 · 被引用次数：18 · 研究领域：Genomics and Rare Diseases、Genomic variations and chromosomal abnormalities、Metabolism and Genetic Disorders

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. A report from the first 2,000 newborns enrolled in the Early Check program, which offered genome screening covering 198 genes associated with early-onset diseases, shows the feasibility and potential clinical utility of the approach, leading to 28 true positive results.