2025/07/31 by Lainie Friedman Ross · 1 voice
Biochemistry, Genetics and Molecular Biology · #Blood disorders and treatments #Genomics and Rare Diseases #Metabolism and Genetic Disorders
paper · pdf · doi:10.1007/s00481-025-00870-9
openalex publication_date 2025/07/31 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/23
Abstract Background Newborn screening (NBS) is a coordinated and comprehensive public health program that includes parent and provider education, the collection of dried blood spot specimens, testing and patient follow-up, outcome tracking, and quality improvement and program evaluation. It was initially developed to identify infants at risk for serious conditions that presented in infancy for which early diagnosis could lead to treatment that would reduce morbidity and mortality. Although NBS for phenylketonuria began before the Wilson and Jungner (W&J) international public health screening guidelines were promulgated in 1968, these guidelines became the backbone for justifying universal screening. The W&J guidelines focused on identifying conditions at an early or presymptomatic stage that require immediate treatment to reduce or prevent morbidity or mortality. Initially, NBS expanded slowly because each condition required its own test, but this changed with tandem mass spectrometry, a platform technology that allowed for screening of multiple conditions with one test. Even more than MS/MS, exome sequencing (ES) or Whole Genome Sequencing (WGS) of newborns has the potential to diagnose many disorders with a single platform technology. Arguments The inclusion of ES or WGS as part of NBS represents a paradigm shift as it would not only identify conditions included in traditional NBS programs but also conditions that present beyond infancy, are not treatable, and/or have variable severity. In this manuscript, I provide 4 critiques against expanding NBS to include routine newborn sequencing: 1) genotype does not necessarily translate into phenotype; 2) phenotype does not always translate into known genotype; and 3) identifying more conditions is not necessarily better; and 4) public health screening should reduce not exacerbate disparities. Conclusion The four critiques against routine newborn sequencing show that the benefits do not clearly outweigh the harms, costs and risks. Supporters must provide evidence of a positive benefit-to-risk ratio. If not, sequencing should not be conducted as part of a universal NBS public health program.