Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Dec;16(12):889-95.
doi: 10.1038/gim.2014.62. Epub 2014 May 29.

Postanalytical tools improve performance of newborn screening by tandem mass spectrometry

Patricia L Hall  1 , Gregg Marquardt  1 , David M S McHugh  1 , Robert J Currier  2 , Hao Tang  2 , Stephanie D Stoway  1 , Piero Rinaldo  1
Affiliations
Free PMC article

Postanalytical tools improve performance of newborn screening by tandem mass spectrometry

Patricia L Hall et al. Genet Med. 2014 Dec.
Free PMC article

Abstract

Purpose: The purpose of this study was to compare performance metrics of postanalytical interpretive tools of the Region 4 Stork collaborative project to the actual outcome based on cutoff values for amino acids and acylcarnitines selected by the California newborn screening program.

Methods: This study was a retrospective review of the outcome of 176,186 subjects born in California between 1 January and 30 June 2012. Raw data were uploaded to the Region 4 Stork Web portal as .csv files to calculate tool scores for 48 conditions simultaneously using a previously unpublished functionality, the tool runner. Scores for individual target conditions were deemed informative when equal or greater to the value representing the first percentile rank of known true-positive cases (17,099 cases in total).

Results: In the study period, the actual false-positive rate and positive predictive value were 0.26 and 10%, respectively. Utilization of the Region 4 Stork tools, simple interpretation rules, and second-tier tests could have achieved a false-positive rate as low as 0.02% and a positive predictive value >50% by replacing the cutoff system with Region 4 Stork tools as the primary method for postanalytical interpretation.

Conclusion: Region 4 Stork interpretive tools, second-tier tests, and other evidence-based interpretation rules could have reduced false-positive cases by up to 90% in California.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The process to upload data batches to the R4S tool runner. Details of the design, content, and clinical utilization of the one-condition tools and dual-scatter plots have been reported previously. A recorded educational presentation is also available at http://www.mayomedicallaboratories.com/articles/hot-topic/2013/06-15-r4s-pt-3/index.html. R4S, Region 4 Stork.
Figure 2
Figure 2
The number of active cutoff values (n = 8,382) used by R4S participating sites (n = 151). The y axis represents the proportion that meets the validation criteria. A given cutoff value is considered validated when it remains within the target range defined in R4S and also within the 25–75 percentile range of all cutoff values posted by all sites. High and low target ranges are defined by percentiles of the cumulative reference and disease ranges but could be replaced by override values in case of significant overlap. Vertical and horizontal dotted lines indicate the median values (active cutoff values = 56; proportion within the validation criteria = 26%). R4S, Region 4 Stork.
Figure 3
Figure 3
The potential impact of R4S tools, interpretation rules, 2TTs, and other potential interventions on the number of FP cases that were reported in California (January to June 2012). (-) Indicates subtraction of cases from the residual FP count on the basis of the criterion listed next to the symbol. 2TT, second-tier test; FP, false positive; R4S, Region 4 Stork.
See this image and copyright information in PMC

References

    1. McHugh D, Cameron CA, Abdenur JE, et al. Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: a worldwide collaborative project. Genet Med. 2011;13:230–254. - PubMed
    1. Watson MS, Mann MY, Lloyd-Puryear MA, Rinaldo P, Howell RR. Newborn screening: toward a uniform screening panel and system [executive summary] Genet Med. 2006;8 suppl:1S–11S. - PubMed
    1. Marquardt G, Currier R, McHugh DM, et al. Enhanced interpretation of newborn screening results without analyte cutoff values. Genet Med. 2012;14:648–655. - PubMed
    1. Merritt JL, 2nd, Vedal S, Abdenur JE, et al. Infants suspected to have very-long chain acyl-CoA dehydrogenase deficiency from newborn screening. Mol Genet Metab. 2014;111:484–492. - PubMed
    1. Rinaldo P, Zafari S, Tortorelli S, Matern D. Making the case for objective performance metrics in newborn screening by tandem mass spectrometry. Ment Retard Dev Disabil Res Rev. 2006;12:255–261. - PubMed

Publication types