Abstract
The expansion of national newborn screening (NBS) programmes has provided significant benefits in the diagnosis and early treatment of several rare, heritable conditions, preventing adverse health outcomes for most affected infants. New technological developments have enabled the implementation of testing panel covering over 50 disorders. Consequently, the increment of false positive rate has led to a high number of healthy infants recalled for expensive and often invasive additional testing, opening a debate about the harm-benefit ratio of the expanded newborn screening. The false-positive rate represents a challenge for healthcare providers working in NBS systems. Here, we give an overview on the most commonly used strategies for decreasing the adverse effects due to inconclusive screening results. The focus is on NBS performance improvement through the implementation of analytical methods, the application of new and more informative biomarkers, and by using post-analytical interpretive tools. These strategies, used as part of the NBS process, can to enhance the positive predictive value of the test and reduce the parental anxiety and healthcare costs related to the unnecessary tests and procedures.
Highlights
There are significant long-term cost benefit advantages in diagnosing inherited metabolic disorders shortly after birth
The amino acid tyrosine was used as the metabolic marker for HT-1, which resulted in a high false positive rate due to the high incidence of benign transient Tyrosinemia in the neonatal population
By selecting appropriate tyrosine cut off levels, other forms of Tyrosinemia (Type II and III) can be identified in which very high levels of tyrosine are present in blood soon after birth
Summary
There are significant long-term cost benefit advantages in diagnosing inherited metabolic disorders shortly after birth. Despite the high sensitivity and specificity of current methods employed in NBS, a positive screening result does not establish a definitive diagnosis and follow-up analytical tests are required. Given that NBS programs include many more disorders requiring more tests than in the past, the rate of false positive results has increased [9]. Adjusting cut off values to reduce the risk of false negatives often has the effect of increasing the false positive rate. Lead to a high number of unnecessary recalls and additional testing which can cause a non-optimal allocation of healthcare resources and parental anxiety with long-term consequences on the child–parent relationship [10]. An evaluation of parental stress highlighted significantly higher levels of anxiety in mothers with newborns in the false-positive group than in mothers whose infants tested negative. Given the psychological and economic impact of false positives, significant efforts have been made to improve the performance of NBS assays
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