Startseite MALDI-MS in first-line screening of newborns for sickle cell disease: results from a prospective study in comparison to HPLC
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

MALDI-MS in first-line screening of newborns for sickle cell disease: results from a prospective study in comparison to HPLC

  • Marven El Osta , Jean-François Benoist ORCID logo , Pierre Naubourg , Stéphane Bonacorsi , Reine Messine , Patrick Ducoroy und Bichr Allaf EMAIL logo
Veröffentlicht/Copyright: 5. Februar 2024
Veröffentlichen auch Sie bei De Gruyter Brill
Manuskript einreichen Informationen für Autor*innen
Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 62 Heft 6

Abstract

Objectives

Newborn screening (NBS) for sickle cell disease (SCD) requires a robust, high-throughput method to detect hemoglobin S (HbS). Screening for SCD is performed by qualitative methods, such as isoelectric focusing (IEF), and both qualitative and quantitative methods such as high performance liquid chromatography (HPLC), capillary electrophoresis (CE), and tandem mass spectrometry (MS/MS). All these methods detect HbS, as well as low-level or absent HbA, and also other variants of hemoglobin. HPLC is considered as a reference method for NBS, because of its high sensitivity and specificity in detecting HbS. NeoSickle®, a fully automated matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) platform, combined with automated sample processing, a laboratory information management system and NeoSickle® software for automatic data interpretation, has increased the throughput of SCD testing. The purpose of this study was to compare the performances of NeoSickle® and HPLC.

Methods

A prospective study was conducted including 9,571 samples from the NBS program to compare MALDI-MS using NeoSickle® with an HPLC method. Correlation between the two methods was studied. For the MALDI-MS method, sensitivity, specificity, NPV, and PPV were calculated.

Results

We found over 99.4 % correlation between the HPLC and MALDI-MS results. NeoSickle® showed 100 % of sensitivity and specificity in detecting SCD syndrome, leading to positive and negative predictive values of 100 %.

Conclusions

NeoSickle® is adapted to NBS for SCD, and can be used in first-line high-throughput screening to detect HbS, and beta-thalassemia major warning. When HbS is detected, second-line use of another specific method as HPLC is necessary.

Keywords: newborn screening; sickle cell disease; HbS; MALDI-TOF; mass spectrometry; HPLC
Corresponding author: Bichr Allaf, Service de Biochimie-Hormonologie, AP-HP, Hôpital Robert Debré, Unité de dépistage néonatal de la drépanocytose en Ile de France, Paris, France, E-mail:

Acknowledgments

The authors would like to thank the staff of the national reference laboratory of Robert-Debré Hospital for their professionalism. We would also like to thank David Marsh who provided editorial assistance.

  1. Research ethics: In accordance with current French law, before sampling, healthcare professionals must inform parents about the newborn screening (NBS) program. Oral information on the nature of the test, its objectives and the diseases screened (Cytic Fibrosis, Phenylketonuria, Adrenal Hyperplasia Congenital, Hypothyroidism, Inborn Errors of Metabolism, and for population at risk: Hemoglobinopathies) must be given. A person with parental authority must give consent for the newborn testing. All procedures were performed in accordance with the 1983 and 2008 revisions of the Declaration of Helsinki. This observational study did not need to be reported to the local Institutional Review Board since it did not change the routine testing by laboratory and it did not change the routine management of patients.

  2. Informed consent: Informed consent was obtained from all individuals who underwent molecular analysis in this study.

  3. Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Competing interests: Mr Marven El Osta Group leader, Biology Group Bimaneo. Mr Patrick Ducoroy CEO Bimaneo. Mr Piere Naubourg Group Leader, IT Group Bimaneo. Biomaneo’s team developed and commercializes Neosickle solution. All other authors state no conflict of interest.

  5. Research funding: None declared.

  6. Data availability: The raw data can be obtained on request from the corresponding author.

References

1. Piel, FB, Steinberg, MH, Rees, DC. Sickle cell disease. N Engl J Med 2017;376:1561–73. https://doi.org/10.1056/nejmra1510865.Suche in Google Scholar

2. Vichinsky, E, Hurst, D, Earles, A, Kleman, K, Lubin, B. Newborn screening for sickle cell disease: effect on mortality. Pediatrics 1988;81:749–55. https://doi.org/10.1542/peds.81.6.749.Suche in Google Scholar

3. Couque, N, Girard, D, Ducrocq, R, Boizeau, P, Haouari, Z, Missud, F, et al.. Improvement of medical care in a cohort of newborns with sickle-cell disease in North Paris: impact of national guidelines. Br J Haematol 2016;173:927–37. https://doi.org/10.1111/bjh.14015.Suche in Google Scholar PubMed

4. Bardakjian, J, Benkerrou, M, Bernaudin, F, Briard, ML, Ducrocq, R, Lambilliotte, A, et al.. Le dépistage néonatal de la drépanocytose en France métropolitaine [Neonatal screening of sickle cell anemia in metropolitan France]. Arch Pediatr 2000;7:1261–3. https://doi.org/10.1016/s0929-693x(00)00140-8.Suche in Google Scholar PubMed

5. Bardakdjian-Michau, J, Bahuau, M, Hurtrel, D, Godart, C, Riou, J, Mathis, M, et al.. Neonatal screening for sickle cell disease in France. J Clin Pathol 2009;62:31–3. https://doi.org/10.1136/jcp.2008.058867.Suche in Google Scholar PubMed

6. Centre National de Coordination de Dépistage Néonatal, CNCDN. Rapport d’activité 2018; 2023. [Online]. Available from: https://depistage-neonatal.fr/wp-content/uploads/2021/07/Rapport-Activite-2018.pdf.Suche in Google Scholar

7. Centre National de Coordination de Dépistage Néonatal, CNCDN. Rapport d’activité 2021; 2023. [Online]. Available from: https://depistage-neonatal.fr/wp-content/uploads/2023/01/Rapport-Activite-2021.pdf.Suche in Google Scholar

8. Daniel, Y, Elion, J, Allaf, B, Badens, C, Bouva, MJ, Brincat, I, et al.. Newborn screening for sickle cell disease in Europe. Int J Neonatal Screening 2019;5:15. https://doi.org/10.3390/ijns5010015.Suche in Google Scholar PubMed PubMed Central

9. Beuzard, Y, Galacteros, F, Braconnier, F, Dubart, A, Chen-Marotel, J, Caburi-Martin, J, et al.. Isoelectric focusing of human hemoglobins. Prog Clin Biol Res 1981;60:177–95.Suche in Google Scholar

10. Eastman, JW, Wong, R, Liao, CL, Morales, DR. Automated HPLC screening of newborns for sickle cell anemia and other hemoglobinopathies. Clin Chem 1996;42:704–10. https://doi.org/10.1093/clinchem/42.5.704.Suche in Google Scholar

11. Murray, C, Hall, SK, Griffiths, P. An evaluation of the Sebia capillarys Neonat Haemoglobin FAST™ system for routine newborn screening for sickle cell disease. Int J Lab Hematol 2011;33:533–9. https://doi.org/10.1111/j.1751-553x.2011.01315.x.Suche in Google Scholar PubMed

12. Moat, SJ, Rees, D, King, L, Ifederu, A, Harvey, K, Hall, K, et al.. Newborn blood spot screening for sickle cell disease by using tandem mass spectrometry: implementation of a protocol to identify only the disease states of sickle cell disease. Clin Chem 2014;60:373–80. https://doi.org/10.1373/clinchem.2013.210948.Suche in Google Scholar PubMed

13. Lobitz, S, Klein, J, Brose, A, Blankenstein, O, Frömmel, C. Newborn screening by tandem mass spectrometry confirms the high prevalence of sickle cell disease among German newborns. Ann Hematol 2019;98:47–53. https://doi.org/10.1007/s00277-018-3477-4.Suche in Google Scholar PubMed

14. Lobitz, S, Telfer, P, Cela, E, Allaf, B, Angastiniotis, M, Backman Johansson, C, et al.. Newborn screening for sickle cell disease in Europe: recommendations from a Pan-European Consensus Conference. Br J Haematol 2018;183:648–60. https://doi.org/10.1111/bjh.15600.Suche in Google Scholar PubMed

15. Allaf, B, Patin, F, Elion, J, Couque, N. New approach to accurate interpretation of sickle cell disease newborn screening by applying multiple of median cutoffs and ratios. Pediatr Blood Cancer 2018;65:e27230. https://doi.org/10.1002/pbc.27230.Suche in Google Scholar PubMed

16. El Osta, M, Naubourg, P, Grunewald, O, Renom, G, Ducoroy, P, Périni, JM. The reliable, automatic classification of neonates in first-tier MALDI-MS screening for sickle cell disease. Int J Neonatal Screening 2019;5:31. https://doi.org/10.3390/ijns5030031.Suche in Google Scholar PubMed PubMed Central

17. Naubourg, P, El Osta, M, Rageot, D, Grunewald, O, Renom, G, Ducoroy, P, et al.. A multicentre pilot study of a two-tier newborn sickle cell disease screening procedure with a first tier based on a fully automated MALDI-TOF MS platform. Int J Neonatal Screening 2019;5:10. https://doi.org/10.3390/ijns5010010.Suche in Google Scholar PubMed PubMed Central

18. Hachani, J, Duban-Deweer, S, Pottiez, G, Renom, G, Flahaut, C, Périni, JM. MALDI-TOF MS profiling as the first-tier screen for sickle cell disease in neonates: matching throughput to objectives. Proteomics Clin Appl 2011;5:405–14. https://doi.org/10.1002/prca.201000093.Suche in Google Scholar PubMed

19. Daniel, Y, Turner, C. Newborn sickle cell disease screening using electrospray tandem mass spectrometry. Int J Neonatal Screening 2018;4:35. https://doi.org/10.3390/ijns4040035.Suche in Google Scholar PubMed PubMed Central

20. Patel, R. Matrix-assisted laser desorption ionization-time of flight mass spectrometry in clinical microbiology. Clin Infect Dis 2013;57:564–72. https://doi.org/10.1093/cid/cit247.Suche in Google Scholar PubMed

21. Lévesque, S, Dufresne, PJ, Soualhine, H, Domingo, MC, Bekal, S, Lefebvre, B, et al.. A side by side comparison of Bruker Biotyper and VITEK MS: utility of MALDI-TOF MS technology for microorganism identification in a public health reference laboratory. PLoS One 2015;10:e0144878. https://doi.org/10.1371/journal.pone.0144878.Suche in Google Scholar PubMed PubMed Central

Received: 2023-11-20
Accepted: 2024-01-23
Published Online: 2024-02-05
Published in Print: 2024-05-27

© 2024 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. SARS-CoV-2 is here to stay: do not lower our guard
  4. Reviews
  5. SARS-CoV-2 subgenomic RNA: formation process and rapid molecular diagnostic methods
  6. Prognostic value of anti-SARS-CoV-2 antibodies: a systematic review
  7. Presence of SARS-CoV-2 RNA in COVID-19 survivors with post-COVID symptoms: a systematic review of the literature
  8. Opinion Papers
  9. Harmonizing the post-analytical phase: focus on the laboratory report
  10. Blood-based biomarkers in Alzheimer’s disease – moving towards a new era of diagnostics
  11. A comprehensive review on PFAS including survey results from the EFLM Member Societies
  12. General Clinical Chemistry and Laboratory Medicine
  13. Report from the HarmoSter study: different LC-MS/MS androstenedione, DHEAS and testosterone methods compare well; however, unifying calibration is a double-edged sword
  14. An LC–MS/MS method for serum cystatin C quantification and its comparison with two commercial immunoassays
  15. CX3CL1/Fractalkine as a biomarker for early pregnancy prediction of preterm premature rupture of membranes
  16. Elevated S100B urine levels predict seizures in infants complicated by perinatal asphyxia and undergoing therapeutic hypothermia
  17. The correlation of urea and creatinine concentrations in sweat and saliva with plasma during hemodialysis: an observational cohort study
  18. Tubular phosphate transport: a comparison between different methods of urine sample collection in FGF23-dependent hypophosphatemic syndromes
  19. Reference Values and Biological Variations
  20. Monocyte distribution width (MDW): study of reference values in blood donors
  21. Data mining of reference intervals for serum creatinine: an improvement in glomerular filtration rate estimating equations based on Q-values
  22. Hematology and Coagulation
  23. MALDI-MS in first-line screening of newborns for sickle cell disease: results from a prospective study in comparison to HPLC
  24. Cardiovascular Diseases
  25. To rule-in, or not to falsely rule-out, that is the question: evaluation of hs-cTnT EQA performance in light of the ESC-2020 guideline
  26. Temporal biomarker concentration patterns during the early course of acute coronary syndrome
  27. Diabetes
  28. Proteomic analysis of diabetic retinopathy identifies potential plasma-protein biomarkers for diagnosis and prognosis
  29. Infectious Diseases
  30. Serum biomarkers of inflammation and vascular damage upon SARS-Cov-2 mRNA vaccine in patients with thymic epithelial tumors
  31. A high throughput immuno-affinity mass spectrometry method for detection and quantitation of SARS-CoV-2 nucleoprotein in human saliva and its comparison with RT-PCR, RT-LAMP, and lateral flow rapid antigen test
  32. Evaluation of inflammatory biomarkers and vitamins in hospitalized patients with SARS-CoV-2 infection and post-COVID syndrome
  33. The CoLab score is associated with SARS-CoV-2 viral load during admission in individuals admitted to the intensive care unit: the CoLaIC cohort study
  34. Development and evaluation of a CRISPR-Cas13a system-based diagnostic for hepatitis E virus
  35. Letters to the Editor
  36. Crioplast® is a reliable device to ensure pre-analytical stability of adrenocorticotrophin (ACTH)
  37. Falsely decreased Abbott Alinity-c gamma-glutamyl transferase-2 result from paraprotein and heparin interference: case report and subsequent laboratory experiments
  38. Impact of hemolysis on uracilemia in the context of dihydropyrimidine dehydrogenase deficiency testing
  39. Value of plasma neurofilament light chain for monitoring efficacy in children with later-onset spinal muscular atrophy under nusinersen treatment
  40. Analytical evaluation of the Snibe β-isomerized C-terminal telopeptide of type I collagen (β-CTX-I) automated method
  41. Acute myeloid leukemia with blue-green neutrophilic inclusions have different outcomes: two cases and review of the literature
  42. Congress Abstracts
  43. The 10+1 Santorini Conference
  44. 14th National Congress of the Portuguese Society of Clinical Chemistry, Genetics and Laboratory Medicine
  45. 15th National Congress of the Portuguese Society of Clinical Chemistry, Genetics and Laboratory Medicine
  46. ISMD2024 Thirteenth International Symposium on Molecular Diagnostics
https://doi.org/10.1515/cclm-2023-1250
Schlagwörter für diesen Artikel
newborn screening; sickle cell disease; HbS; MALDI-TOF; mass spectrometry; HPLC

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. SARS-CoV-2 is here to stay: do not lower our guard
  4. Reviews
  5. SARS-CoV-2 subgenomic RNA: formation process and rapid molecular diagnostic methods
  6. Prognostic value of anti-SARS-CoV-2 antibodies: a systematic review
  7. Presence of SARS-CoV-2 RNA in COVID-19 survivors with post-COVID symptoms: a systematic review of the literature
  8. Opinion Papers
  9. Harmonizing the post-analytical phase: focus on the laboratory report
  10. Blood-based biomarkers in Alzheimer’s disease – moving towards a new era of diagnostics
  11. A comprehensive review on PFAS including survey results from the EFLM Member Societies
  12. General Clinical Chemistry and Laboratory Medicine
  13. Report from the HarmoSter study: different LC-MS/MS androstenedione, DHEAS and testosterone methods compare well; however, unifying calibration is a double-edged sword
  14. An LC–MS/MS method for serum cystatin C quantification and its comparison with two commercial immunoassays
  15. CX3CL1/Fractalkine as a biomarker for early pregnancy prediction of preterm premature rupture of membranes
  16. Elevated S100B urine levels predict seizures in infants complicated by perinatal asphyxia and undergoing therapeutic hypothermia
  17. The correlation of urea and creatinine concentrations in sweat and saliva with plasma during hemodialysis: an observational cohort study
  18. Tubular phosphate transport: a comparison between different methods of urine sample collection in FGF23-dependent hypophosphatemic syndromes
  19. Reference Values and Biological Variations
  20. Monocyte distribution width (MDW): study of reference values in blood donors
  21. Data mining of reference intervals for serum creatinine: an improvement in glomerular filtration rate estimating equations based on Q-values
  22. Hematology and Coagulation
  23. MALDI-MS in first-line screening of newborns for sickle cell disease: results from a prospective study in comparison to HPLC
  24. Cardiovascular Diseases
  25. To rule-in, or not to falsely rule-out, that is the question: evaluation of hs-cTnT EQA performance in light of the ESC-2020 guideline
  26. Temporal biomarker concentration patterns during the early course of acute coronary syndrome
  27. Diabetes
  28. Proteomic analysis of diabetic retinopathy identifies potential plasma-protein biomarkers for diagnosis and prognosis
  29. Infectious Diseases
  30. Serum biomarkers of inflammation and vascular damage upon SARS-Cov-2 mRNA vaccine in patients with thymic epithelial tumors
  31. A high throughput immuno-affinity mass spectrometry method for detection and quantitation of SARS-CoV-2 nucleoprotein in human saliva and its comparison with RT-PCR, RT-LAMP, and lateral flow rapid antigen test
  32. Evaluation of inflammatory biomarkers and vitamins in hospitalized patients with SARS-CoV-2 infection and post-COVID syndrome
  33. The CoLab score is associated with SARS-CoV-2 viral load during admission in individuals admitted to the intensive care unit: the CoLaIC cohort study
  34. Development and evaluation of a CRISPR-Cas13a system-based diagnostic for hepatitis E virus
  35. Letters to the Editor
  36. Crioplast® is a reliable device to ensure pre-analytical stability of adrenocorticotrophin (ACTH)
  37. Falsely decreased Abbott Alinity-c gamma-glutamyl transferase-2 result from paraprotein and heparin interference: case report and subsequent laboratory experiments
  38. Impact of hemolysis on uracilemia in the context of dihydropyrimidine dehydrogenase deficiency testing
  39. Value of plasma neurofilament light chain for monitoring efficacy in children with later-onset spinal muscular atrophy under nusinersen treatment
  40. Analytical evaluation of the Snibe β-isomerized C-terminal telopeptide of type I collagen (β-CTX-I) automated method
  41. Acute myeloid leukemia with blue-green neutrophilic inclusions have different outcomes: two cases and review of the literature
  42. Congress Abstracts
  43. The 10+1 Santorini Conference
  44. 14th National Congress of the Portuguese Society of Clinical Chemistry, Genetics and Laboratory Medicine
  45. 15th National Congress of the Portuguese Society of Clinical Chemistry, Genetics and Laboratory Medicine
  46. ISMD2024 Thirteenth International Symposium on Molecular Diagnostics
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2025 De Gruyter Brill
Heruntergeladen am 13.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/cclm-2023-1250/html
Button zum nach oben scrollen