State Newborn Screening in the Tandem Mass Spectrometry Era: More Tests, More False-Positive Results

@article{Tarini2006StateNS,
  title={State Newborn Screening in the Tandem Mass Spectrometry Era: More Tests, More False-Positive Results},
  author={Beth A. Tarini and Dimitri A. Christakis and H. Gilbert Welch},
  journal={Pediatrics},
  year={2006},
  volume={118},
  pages={448 - 456}
}
BACKGROUND. The advent of tandem mass spectrometry has made it possible to test newborns for multiple conditions efficiently. It is not known how state newborn screening programs have changed screening practices in response to this technology and how it affects the number of false-positive test results. METHODS. We obtained data from the National Newborn Screening and Genetics Resource Center regarding the screening practices for each of the 50 states, to determine the number of mandated… 

Figures and Tables from this paper

Making the case for objective performance metrics in newborn screening by tandem mass spectrometry.
TLDR
The repeat rate and the proportion of cases with abnormal findings actually been reported are new metrics proposed here as an objective mean to express the overall noise in a program, where noise is defined as the total number of abnormal results obtained using a given set of cut-off values.
Expanded newborn screening and confirmatory follow-up testing for inborn errors of metabolism detected by tandem mass spectrometry
  • T. Ozben
  • Medicine
    Clinical chemistry and laboratory medicine
  • 2013
TLDR
This review covers some of the basic theory of expanded MS/MS and follow-up confirmatory tests applied for NBS of IEM, a coordinated comprehensive system consisting of education, screening, follow- up of abnormal test results, confirmatory testing, diagnosis, treatment, and evaluation of periodic outcome and efficiency.
Expanded newborn screening by mass spectrometry: New tests, future perspectives.
TLDR
The new challenge for the future will be reducing the false positive rate by using second-tier tests, avoiding false negative results by using new specific biomarkers and introducing new treatable disorders in NBS programs.
False-positive Results in Expanded Newborn Screening
TLDR
The authors seem to have joined a cadre of nonclinician academicians (including those with primary interest in bioethics, evaluative clinical sciences, and outcomes groups with no firsthand experience in caring for inborn errors of metabolism) in criticizing this important advance.
LC-MS/MS progress in newborn screening.
Progress in expanded newborn screening for metabolic conditions by LC-MS/MS in Tuscany: Update on methods to reduce false tests
TLDR
Adjustments to cut-off values, the introduction of a second-tier test for propionic acidaemia and for methylmalonic aciduria, the inclusion of succinylacetone in the panel of metabolites, and protocols for premature infants and for newborns on parenteral nutrition or transfused resulted in a reduction in recalls.
Postanalytical tools improve performance of newborn screening by tandem mass spectrometry
TLDR
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.
Development of Strategies to Decrease False Positive Results in Newborn Screening
TLDR
An overview on the most commonly used strategies for decreasing the adverse effects due to inconclusive screening results and 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.
New Advances for Newborn Screening of Inborn Errors of Metabolism by Capillary Electrophoresis-Mass Spectrometry (CE-MS).
TLDR
Recent advances using capillary electrophoresis-mass spectrometry (CE-MS) for reliable second-tier screening or confirmatory testing based on targeted analysis of amino acids, acylcarnitines, nucleosides, and other classes of polar metabolites associated with IEMs are described.
Newborn screening: current status.
  • P. Arn
  • Medicine
    Health affairs
  • 2007
TLDR
Newborn screening, which represents one of the major advances in child health of the past century, has been carried out in all fifty U.S. states since the 1970s and raises many policy issues including screening's cost- effectiveness, ethics, quality, and oversight.
...
...

References

SHOWING 1-10 OF 40 REFERENCES
Screening newborns for inborn errors of metabolism by tandem mass spectrometry.
TLDR
More cases of inborn errors of metabolism are diagnosed by screening with tandem mass spectrometry than are diagnosed clinically, and which patients with disorders diagnosed by such screening would have become symptomatic if screening had not been performed.
Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications.
TLDR
The screening by MS/MS for up to 23 additional disorders has approximately doubled the detection rate compared with that achieved by the conventional methods used in Germany.
The magnitude and challenge of false-positive newborn screening test results.
TLDR
The magnitude of false-positive results generated in newborn screening programs, particularly for congenital endocrinopathies, presents a great challenge for future improvement of this important public health program.
A pilot study of neonatal screening by electrospray ionization tandem mass spectrometry in Taiwan.
  • W. Lin, J. Y. Wu, D. Niu
  • Medicine
    Acta paediatrica Taiwanica = Taiwan er ke yi xue hui za zhi
  • 2001
TLDR
ESI/MS/MS is proven to be an adequate tool for inborn metabolic error screening and screened 2100 newborns to establish the normal amino acid and acylcarnitine level.
Tandem mass spectrometry in newborn screening.
  • L. Stokowski
  • Medicine
    Advances in neonatal care : official journal of the National Association of Neonatal Nurses
  • 2003
Modifications in electrospray tandem mass spectrometry for a neonatal-screening pilot study in Japan.
Tandem mass spectrometric analysis for amino, organic, and fatty acid disorders in newborn dried blood spots: a two-year summary from the New England Newborn Screening Program.
TLDR
In screening for 23 metabolic disorders by MS/MS, an mean positive predictive value of 8% can be achieved when using cutoffs for individual markers determined empirically on newborns.
Newborn screening: toward a uniform screening panel and system.
  • Medicine
    Genetics in medicine : official journal of the American College of Medical Genetics
  • 2006
The Maternal and Child Health Bureau commissioned the American College of Medical Genetics to outline a process for the standardization of outcomes and guidelines for state newborn screening programs
New developments in neonatal screening
TLDR
The combination of the development of generic analytical technology of great power and sophistication, and the discovery of new treatable metabolic diseases detectable in the newborn period, has resulted in a sea change in neonatal screening.
...
...