Postanalytical tools improve performance of newborn screening by tandem mass spectrometry

• Type of Material: Article
• Authors: Patricia Hall, Emory University; Gregg Marquardt, Mayo Clinic; David M.S. McHugh, Mayo Clinic; Robert J. Currier, California Department of Public Heath; Hao Tang, California Department of Public Heath; Stephanie D. Stoway, Mayo Clinic; Piero Rinaldo, Mayo Clinic
• Language: English
• Date: 2014-05-29
• Publisher: Nature Publishing Group: Open Access Hybrid Model Option B
• Publication Version: Final Published Version
• Copyright Statement: © American College of Medical Genetics and Genomics
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1038/gim.2014.62
• Title of Journal or Parent Work: Genetics in Medicine
• ISSN: 1098-3600
• Volume: 16
• Issue: 12
• Start Page: 889
• End Page: 895
• Grant/Funding Information: This project was supported by a grant (U22MC03963) to the Region 4 Genetics Collaborative from the Health Resources and Service Administration of the Maternal and Child Health Bureau Cooperative Agreement, by contracts from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contract no. HHSN275201000017C) and the Newborn Screening Translational Research Network (subcontract no. HHSN275200800001C 01), and by the T. Denny Sanford Professorship fund, Mayo Clinic.
• Keywords: tandem mass spectrometry; QUANTIFICATION; HEALTH; DISORDERS; cutoff values; Genetics & Heredity; REDUCTASE DEFICIENCY; FOLLOW-UP; DRIED BLOOD SPOTS; Life Sciences & Biomedicine; newborn screening; AMINO-ACIDS; DISEASE; DEFECTS; second-tier test; postanalytical interpretive tools; Science & Technology
• Research Categories: Health Sciences, Public Health

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the Region 4 Stork Web portal as.csv files to calculate tool scores for 48 conditions simultaneously using a previously unpublished functionality, the tool runner.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.