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

Clinical Snapshot

Key Findings

• P Value: Not applicable for descriptive feasibility study

• Effect Size: 2.5% screen positive rate (50/1,979 newborns)

• Primary Outcome: Feasibility and clinical utility of expanded genomic newborn screening

• Nnt Or Sensitivity: 55% true positive rate among screen positives (28/50), indicating positive predictive value of 55%

• Confidence Interval: Not reported

Clinical Application

Technically feasible using existing dried blood spot infrastructure, though requires significant genetic counseling resources and systematic follow-up protocols Relevant to Australian newborn screening programs, though would require TGA approval for expanded genomic testing and integration with existing state-based screening programs. Cost-effectiveness analysis needed for PBS consideration. Newborns in healthcare systems with established newborn screening programs and genetic counseling infrastructure

Abstract

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.

References

1. 1.Cope, H. L., Jalazo, E. R., Berg, J. S., Sullivan, J. A., Kucera, K. S., Shone, S. M., Frawley, H. E., Gwaltney, A. Y., Forsythe, A. N., Migliore, B. A., Wright, B., Moultrie, R. R., Milko, L. V., Zimmerman, R. S., Kruszka, P., Suchy, S. F., Begtrup, A., Langley, K. G., Monaghan, K. G., Kraczkowski, C., Guenzel, A. J., McWalter, K., Hruska, K. S., Bailey, D. B., Wheeler, A. C., Raspa, M., Powell, C. M., & Peay, H. L. (2025). Feasibility and clinical utility of expanded genomic newborn screening in the Early Check program. Nature Medicine. https://doi.org/10.1038/s41591-025-03945-8