Combined genetic screening and traditional biochemical screening to optimize newborn screening systems

Newborn screening can detect around 40 different diseases based on biochemical indicators and has resulted in the improved quality of life for children suffering from genetic diseases. However, NBS is limited as it does not cover all genetic diseases in newborns and has high rates of false positives and negatives. Genetic screening can be used to address the shortcomings of traditional biochemical screening, however, the comprehensive clinical value of genetic screening is yet to be systematically studied. In this study, we used two different genetic screening methods to examine 200 cases of NBS. We found that genetic screening can be used to identify a broader spectrum of diseases and is not limited to traditional biochemical screening diseases; it can identify positive cases of disease and can eliminate false positives caused by multiple factors such as pathogenic variants carrier or the mode of childbirth. Genetic screening has shortened the time to diagnosis and reduced the costs of testing. Furthermore, we found that the biochemical detection results were limited when patients simultaneously carried multiple pathogenic mutations. Our research provisionally demonstrates the necessity, feasibility and significance of clinical genetic screening in newborns and provides a solid basis for future clinical developments.