State-of-the-art for DNA technology in newborn screening

Just as metabolites, hormones and proteins are measured in newborn screening tests, DNA has become an analyte that is important in the screens for certain disorders. DNA confirmatory testing on the original dried blood specimen reduces the age at diagnostic confirmation and antibiotic prophylaxis initiation for neonates with sickle cell disease. Molecular genetic analysis of the initial specimens from newborns with elevated immunoreactive trypsinogen (IRT) for cystic fibrosis (CF) screening permits reduction of the IRT threshold value, improving specificity without compromising sensitivity. Because of this cost reduction, CF neonatal screening programs routinely incorporate DNA confirmatory testing into their initial CF screening algorithm. DNA analysis is also a valuable adjunct in screening programs for congenital adrenal hyperplasia (CAH), improving sensitivity and specificity. Incorporation of DNA into newborn screening programs will continue to be stimulated by development of robust, high throughput technologies for evaluation of this analyte. New paradigms for neonatal screening are evolving, including hearing screening in the newborn nursery. DNA testing, such as for mutations in the connexin 26 gene, may have a role in the evaluation of those screened positive. Newborn screening dried blood specimens are DNA databases. Therefore, there are significant ethical, legal and social issues that must be considered in the storage and utilization of neonatal screening specimens.