Elsevier

Genetics in Medicine

Volume 14, Issue 7, July 2012, Pages 648-655
Genetics in Medicine

Original Research Article
Enhanced interpretation of newborn screening results without analyte cutoff values

https://doi.org/10.1038/gim.2012.2Get rights and content
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Abstract

Purpose

To improve quality of newborn screening by tandem mass spectrometry with a novel approach made possible by the collaboration of 154 laboratories in 49 countries.

Methods

A database of 767,464 results from 12,721 cases affected with 60 conditions was used to build multivariate pattern recognition software that generates tools integrating multiple clinically significant results into a single score. This score is determined by the overlap between normal and disease ranges, penetration within the disease range, differences between conditions, and weighted correction factors.

Results

Ninety tools target either a single condition or the differential diagnosis between multiple conditions. Scores are expressed as the percentile rank among all cases with the same condition and are compared to interpretation guidelines. Retrospective evaluation of past cases suggests that these tools could have avoided at least half of 279 false-positive outcomes caused by carrier status for fatty-acid oxidation disorders and could have prevented 88% of known false-negative events.

Conclusion

Application of this computational approach to raw data is independent from single analyte cutoff values. In Minnesota, the tools have been a major contributing factor to the sustained achievement of a false-positive rate below 0.1% and a positive predictive value above 60%.

Genet Med advance online publication 16 February 2012

Keywords

cutoff values
false-positive rate
inborn errors of metabolism
newborn screening
positive predictive value

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