1 research outputs found
Enhanced interpretation of newborn screening results without analyte cutoff values
A collaboration among 157 newborn screening programs in 47 countries has lead to the
creation of a database of 705,333 discrete analyte concentrations from 11,462 cases affected with
57 metabolic disorders, and from 631 heterozygotes for 12 conditions. This evidence was first
applied to establish disease ranges for amino acids and acylcarnitines, and clinically validate 114
cutoff target ranges.
Objective: To improve quality and performance with an evidence-based approach, multivariate
pattern recognition software has been developed to aid in the interpretation of complex analyte
profiles. The software generates tools that convert multiple clinically significant results into a
single numerical score based on overlap between normal and disease ranges, penetration within
the disease range, differences between specific conditions, and weighted correction factors.
Design: Eighty-five on-line tools target either a single condition or the differential diagnosis
between two or more conditions. Scores are expressed as a numerical value and as the percentile
rank among all cases with the condition chosen as primary target, and are compared to
interpretation guidelines. Tools are updated automatically after any new data submission (2009-
2011: 5.2 new cases added per day on average).
Main outcome measures: Retrospective evaluation of past cases suggest that these tools could
have avoided at least half of 277 false positive outcomes caused by carrier status for fatty acid
oxidation disorders, and could have prevented 88% of false negative events caused by cutoff
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values set inappropriately. In Minnesota, their prospective application has been a major
contributing factor to the sustained achievement of a false positive rate below 0.1% and a
positive predictive value above 60%.
Conclusions: Application of this computational approach to raw data could make cutoff values
for single analytes effectively obsolete. This paradigm is not limited to newborn screening and is
applicable to the interpretation of diverse multi-analyte profiles utilized in laboratory medicine.
Abstract wor