Figure 2. Scaling technologies for newborn screening.

Traditional newborn screens were developed one test at a time and focused on a single disease (top left), with later technologies such as tandem mass spectrometry expanding the approach to evaluate many analytes at a time (bottom left). Both led to identification of a limited scope of diseases and were added to newborn screening panels in a methodical, but often slow, fashion. In contrast, whole genome sequencing in theory can identify any and all diseases in a single test, but at a cost that includes the need for broader, pan-ethnic data bases of genomic sequence to allow definitive classification of variants as pathogenic or benign. The sequence can also be carried forward to allow screening or testing for diseases across a lifetime. In reality, a combination of molecular and functional testing is likely to provide the most robust outcomes in a comprehensive NBS program.