title: MALDI-TOF MS profiling as the first-tier screen for sickle cell disease in neonates: matching throughput to objectives.
abstract: OBJECTIVE
  Universal newborn screening for sickle cell diseases (SCDs) is not currently performed in many countries concerned by this public health problem. Owing to the technical and financial limitations of standard profiling methods (IEF coupled to subsequent HPLC), ethnically targeted neonatal screening is often preferred. Here, we demonstrate that MALDI-MS-based SCD newborn screening could be considered as a potential method for a strategy to universal screening because of its high throughput, cost-effectiveness, sensitivity and ability to automatically discriminate sickle haemoglobin.
  
  
  METHODS
  We carried out a retrospective study of dried blood spots from 844 Guthrie cards. Four determinations of 1000 mass spectra were performed from each tested dried blood spot.
  
  
  RESULTS
  The MALDI-MS-based screening was highly correlated with the reference method. Only 2.3% of the samples presented a poor spectral quality.
  
  
  CONCLUSIONS
  Given that the overall acquisition, data reprocessing and software-assisted classification (ClinProTools™) time for processing four mass determinations (corresponding to one sample) was around 1 min, 1000 samples can be analysed per day. Rather than seeking to detect as many different haemoglobinopathies as possible, it would become possible to use MALDI-TOF-MS to screen (at a constant cost) as many samples as possible for sickle cell disease.
authors.affiliation: University Lille Nord de France, Lille, France.
authors.forename: Johan
authors.initials: J
authors.lastname: Hachani
authors.forename: Sophie
authors.initials: S
authors.lastname: Duban-Deweer
authors.forename: Gwënaël
authors.initials: G
authors.lastname: Pottiez
authors.forename: Gilles
authors.initials: G
authors.lastname: Renom
authors.forename: Christophe
authors.initials: C
authors.lastname: Flahaut
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Périni
mesh_terms: D000755:Anemia, Sickle Cell / Q000175:diagnosis* / Q000191:economics / Q000473:pathology; D016022:Case-Control Studies; D003362:Cost-Benefit Analysis; D005260:Female; D006451:Hemoglobin, Sickle / Q000032:analysis*; D057166:High-Throughput Screening Assays / Q000191:economics / Q000379:methods*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening / Q000191:economics / Q000379:methods*; D011634:Public Health; D011786:Quality Control; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000191:economics / Q000379:methods*
chemical_list: D006451:Hemoglobin, Sickle