How to decrease the number of false-positive newborns while increasing performance and adaptability of newborn screening (NBS) – use of targeted next-generation sequencing (NGS) in NBS

Decreasing false-positive newborns while increasing performance and adaptability of newborn screening using targeted next-generation sequencing​.​

A research project by Alberte A. Lundquist

Newborn screening (NBS) is a public health programme for early diagnosis of treatable, mostly genetic, diseases, where early treatment in a latent stage of disease can prevent disease manifestations and death. Methods of screening in Denmark involve biochemical determination of analytes as first-tier testing. Molecular genetic studies are only used as first-tier testing when screening for severe combined immunodeficiency (SCID) and as second-tier testing combined with further biochemical methods for confirmative evaluation of screen positive samples. Although the NBS performs well, false positives are still a matter of concern emphasizing the possible stress on the families and investigations on newborns that may include both expensive and invasive additional testing. 

This study will search to find algorithms to decrease the number of NBS false positives, while simultaneously increasing performance and adaptability of NBS, using targeted next-generation sequencing. It will also investigate patients with a false positive result, including false positive newborns with raised C5OH without having HLSCD, and the relation to vulnerable child syndrome and morbidity. The initially obtained filter paper bloodspot sample of screened newborns will be used for analyses. 

Expectantly, this study will initiate further studies to implement the full potential of NBS by increasing our knowledge about the morbidity of patients with false positive results and the use of NGS in NBS.


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