Newborn screening in the 1980s-the automation of follow-up

X-linked adrenoleukodystrophy (ALD) is a recent addition to the Recommended Uniform Screening Panel, prompting many states to begin screening newborns for the disorder. We provide California’s experience with ALD newborn screening, highlighting the clinical and epidemiological outcomes observed as well as program implementation challenges. In this retrospective cohort study, we examine ALD newborn screening results and clinical outcomes for 1,854,631 newborns whose specimens were received by the California Genetic Disease Screening Program from 16 February 2016 through 15 February 2020. In the first four years of ALD newborn screening in California, 355 newborns screened positive for ALD, including 147 (41%) with an ABCD1 variant of uncertain significance (VUS) and 95 males diagnosed with ALD. After modifying cutoffs, we observed an ALD birth prevalence of 1 in 14,397 males. Long-term follow-up identified 14 males with signs of adrenal involvement. This study adds to a growing body of literature reporting on outcomes of newborn screening for ALD and offering a glimpse of what other large newborn screening programs can expect when adding ALD to their screening panel.

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Mass Spectrometry but Not Fluorimetry Distinguishes Affected and Pseudodeficiency Patients in Newborn Screening for Pompe Disease

Clinical Chemistry ◽

10.1373/clinchem.2016.269027 ◽

2017 ◽

Vol 63 (7) ◽

pp. 1271-1277 ◽

Cited By ~ 20

Author(s):

Hsuan-Chieh Liao ◽

Min-Ju Chan ◽

Chia-Feng Yang ◽

Chuan-Chi Chiang ◽

Dau-Ming Niu ◽

...

Keyword(s):

Mass Spectrometry ◽

Newborn Screening ◽

Pompe Disease ◽

Late Onset ◽

Asian Population ◽

Dried Blood Spots ◽

Fluorimetric Assay ◽

Analytical Range ◽

Patient Referrals

Abstract BACKGROUND Deficiency of the lysosomal enzyme acid α-glucosidase (GAA) causes Pompe disease. Newborn screening for Pompe disease is ongoing, and improved methods for distinguishing affected patients from those with pseudodeficiency, especially in the Asian population, would substantially reduce the number of patient referrals for clinical follow-up. METHODS We measured the enzymatic activity of GAA in dried blood spots on newborn screening cards (DBS) using a tandem mass spectrometry (MS/MS) assay. The assay displayed a relatively large analytical range compared to the fluorimetric assay with 4-methylumbelliferyl-α-glucoside. DBS from newborns confirmed to have infantile-onset Pompe disease (IOPD, n = 11) or late-onset Pompe disease (LOPD) (n = 12) and those from patients bearing pseudodeficiency alleles with or without Pompe mutations, or Pompe disease carriers (n = 230) were studied. RESULTS With use of the MS/MS GAA assay in DBS, 96% of the pseudodeficiency newborns and all of the Pompe disease carriers were well separated from the IOPD and LOPD newborns. The fluorimetric assay separated <10% of the pseudodeficiencies from the IOPD/LOPD group. CONCLUSIONS The relatively large analytical range MS/MS GAA assay but not the fluorimetric assay in DBS provides a robust approach to reduce the number of referrals and should dramatically facilitate newborn screening of Pompe disease.

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Newborn Screening for Cystic Fibrosis

PEDIATRICS ◽

10.1542/peds.87.6.954 ◽

1991 ◽

Vol 87 (6) ◽

pp. 954-955

Author(s):

IAN C. T. LYON ◽

DIANNE R. WEBSTER

Keyword(s):

Cystic Fibrosis ◽

Newborn Screening ◽

Elevated Level ◽

Meconium Ileus ◽

Screening Tests ◽

Initial Screening ◽

False Negatives ◽

Immunoreactive Trypsinogen

To the Editor.— The report on newborn screening for cystic fibrosis1 illustrates the need for continued evaluation of such programs. The authors state that the identification of cases of cystic fibrosis (CF) by an elevated level of immunoreactive trypsinogen (IRT) in second (follow-up) samples from infants with positive initial screening tests could result in false negatives in 27% of cases of cystic fibrosis without meconium ileus (MI). We have screened 401 122 infants using the method originally reported.2

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The context and approach for the California newborn screening short- and long-term follow-up data system: Preliminary findings

Genetics in Medicine ◽

10.1097/gim.0b013e3181fe5d66 ◽

2010 ◽

Vol 12 ◽

pp. S242-S250 ◽

Cited By ~ 21

Author(s):

Lisa Feuchtbaum ◽

Sunaina Dowray ◽

Fred Lorey

Keyword(s):

Newborn Screening ◽

Data System ◽

Long Term Follow Up ◽

Short And Long Term

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Long-term follow-up of newborn screening patients

Genetics in Medicine ◽

10.1097/gim.0b013e3181fea476 ◽

2010 ◽

Vol 12 ◽

pp. S267-S268 ◽

Cited By ~ 6

Author(s):

Susan A. Berry ◽

Michele A. Lloyd-Puryear ◽

Michael S. Watson

Keyword(s):

Newborn Screening ◽

Long Term Follow Up

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Long-term follow-up to ensure quality care of individuals diagnosed with newborn screening conditions: Early experience in New England

Genetics in Medicine ◽

10.1097/gim.0b013e3181fe5d37 ◽

2010 ◽

Vol 12 ◽

pp. S220-S227 ◽

Cited By ~ 8

Author(s):

Inderneel Sahai ◽

Roger B. Eaton ◽

Jaime E. Hale ◽

Eleanor A. Mulcahy ◽

Anne Marie Comeau

Keyword(s):

Newborn Screening ◽

New England ◽

Quality Care ◽

Early Experience ◽

Long Term Follow Up

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National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Follow-Up Testing for Metabolic Disease Identified by Expanded Newborn Screening Using Tandem Mass Spectrometry; Executive Summary

Clinical Chemistry ◽

10.1373/clinchem.2009.131300 ◽

2009 ◽

Vol 55 (9) ◽

pp. 1615-1626 ◽

Cited By ~ 54

Author(s):

Dennis J Dietzen ◽

Piero Rinaldo ◽

Ronald J Whitley ◽

William J Rhead ◽

W Harry Hannon ◽

...

Keyword(s):

Mass Spectrometry ◽

Amino Acids ◽

Tandem Mass Spectrometry ◽

Organic Acids ◽

Newborn Screening ◽

Tandem Mass ◽

Confirmatory Testing ◽

The Us ◽

The Impact

Abstract Background: Almost all newborns in the US are screened at birth for multiple inborn errors of metabolism using tandem mass spectrometry. Screening tests are designed to be sufficiently sensitive so that cases are not missed. The NACB recognized a need for standard guidelines for laboratory confirmation of a positive newborn screen such that all babies would benefit from equal and optimal follow-up by confirmatory testing. Methods: A committee was formed to review available data pertaining to confirmatory testing. The committee evaluated previously published guidelines, published methodological and clinical studies, clinical case reports, and expert opinion to support optimal confirmatory testing. Grading was based on guidelines adopted from criteria derived from the US Preventive Services Task Force and on the strength of recommendations and the quality of the evidence. Three primary methods of analyte measurement were evaluated for confirmatory testing including measurement of amino acids, organic acids, and carnitine esters. The committee graded the evidence for diagnostic utility of each test for the screened conditions. Results: Ample data and experience were available to make strong recommendations for the practice of analyzing amino acids, organic acids, and acylcarnitines. Likewise, strong recommendations were made for the follow-up test menu for many disorders, particularly those with highest prevalence. Fewer data exist to determine the impact of newborn screening on patient outcomes in all but a few disorders. The guidelines also provide an assessment of developing technology that will fuel a refinement of current practice and ultimate expansion of the diseases detectable by tandem mass spectrometry. Conclusions: Guidelines are provided for optimal follow-up testing for positive newborn screens using tandem mass spectrometry. The committee regards these tests as reliable and currently optimal for follow-up testing. .

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Implementing a tracking system for confirmatory diagnostic results after positive newborn screening for cystic fibrosis—implications for process quality and patient care

European Journal of Pediatrics ◽

10.1007/s00431-020-03849-4 ◽

2020 ◽

Author(s):

Gwendolyn Gramer ◽

Inken Brockow ◽

Christiane Labitzke ◽

Junmin Fang-Hoffmann ◽

Andreas Beivers ◽

...

Keyword(s):

Cystic Fibrosis ◽

Newborn Screening ◽

Patient Care ◽

Tracking System ◽

Process Quality ◽

Federal State ◽

Cost Calculation ◽

Confirmatory Testing ◽

Before And After

Abstract Newborn screening for cystic fibrosis (CF-NBS) was introduced in Germany in 2016. Currently, systematic follow-up of positive CF-NBS results is not implemented or reimbursed in the NBS program. We investigated results of confirmatory testing over 24 months after implementation of CF-NBS for a large German NBS center before and after introduction of an active tracking system and performed a cost calculation for tracking. Results are compared with the federal state of Bavaria, where a centralized tracking system has been in place for many years. At the NBS center, 244 of 281,907 children had a positive CF-NBS result requiring diagnostic confirmation. Before implementation of a telephone tracking system, only 43% of confirmatory results were returned despite repeated written requests. The consecutive strategy including telephone tracking led to an increase of resolved cases to 84%. However, the centralized tracking system in Bavaria, assigning children with positive CF-NBS directly to a responsible CF-center, resolved 99% of cases. The calculated additional cost for a tracking system in Germany including telephone tracking is 1.20€ per newborn screened. Conclusion: The implementation of a tracking system achieves a distinct improvement in CF-NBS with justifiable costs. The effect can be limited by absence of centralized organization of confirmatory testing. What is Known:• Newborn screening for cystic fibrosis (CF-NBS) has been performed for many years in several countries worldwide• While many studies have focused on different CF-NBS strategies, the organization of confirmatory testing and process quality concerning returned information to the NBS center has so far received less attention. What is New:• The implementation of an active tracking system achieves a distinct improvement of clarified cases after positive CF-NBS with justifiable costs.• The effect of a tracking system can be limited by the absence of a centralized organization of confirmatory testing.

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Implementing Statewide Newborn Screening for New Disorders: U.S. Program Experiences

International Journal of Neonatal Screening ◽

10.3390/ijns6020035 ◽

2020 ◽

Vol 6 (2) ◽

pp. 35 ◽

Cited By ~ 2

Author(s):

Yvonne Kellar-Guenther ◽

Sarah McKasson ◽

Kshea Hale ◽

Sikha Singh ◽

Marci K. Sontag ◽

...

Keyword(s):

Newborn Screening ◽

Screening Program ◽

Muscular Atrophy ◽

Survival Curve ◽

Type I ◽

Mucopolysaccharidosis Type I ◽

Newborn Screening Program ◽

Mps I ◽

Insight Into

Data were collected from 39 newborn screening (NBS) programs to provide insight into the time and factors required for implementing statewide screening for Pompe, Mucopolysaccharidosis type I (MPS I), adrenoleukodystrophy (ALD), and Spinal Muscular Atrophy (SMA). Newborn screening program readiness to screen statewide for a condition was assessed using four phases: (1) approval to screen; (2) laboratory, follow-up, and information technology capabilities; (3) education; and (4) implementation of statewide newborn screening. Seventeen states (43.6%) reached statewide implementation for at least one new disorder. Those states reported that it took 28 months to implement statewide screening for Pompe and MPS I, 30.5 months for ALD, and 20 months for SMA. Using survival curve analysis to account for states still in progress, the estimated median time to statewide screening increased to 75 months for Pompe and 66 months for MPS I. When looking at how long each readiness component took to complete, laboratory readiness was one of the lengthier processes, taking about 39 months. Collaboration with other NBS programs and hiring were the most frequently mentioned facilitators to implementing newborn screening. Staffing or inability to hire both laboratory and follow-up staff was the most frequently mentioned barrier.

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