title: Detection of TPN contamination of dried blood spots used in newborn and metabolic screening and its impact on quantitative measurement of amino acids.
abstract: BACKGROUND
  Markers derived from dextrose (d-glucose) are observed in the MS/MS-based acylcarnitine profiles from dried-blood spots of some premature infants receiving intravenous nutrition. The presence of these markers at m/z 325, 399 and 473 are thought to arise from contamination of blood by total parenteral nutrition (TPN) solutions during specimen collection from premature infants. These solutions contain high concentrations of amino acids and as a result, false-positive screening results for amino acid disorders may occur. This study investigates quantitative parameters of dextrose and amino acids in blood samples enriched with different TPN solutions.
  
  
  METHODS
  Whole blood collected in heparin was enriched with three different TPN solutions containing 5, 10 or 12.5% dextrose and amino acids that were originally prepared for delivery of 2.5, 3 or 4 g/kg/day of Premasol® then spotted onto filter paper cards. Acylcarnitine and amino acid profiles using MS/MS were obtained. Ion ratios of dextrose relative to specific acylcarnitine stable isotope internal standards and amino acid concentrations were obtained.
  
  
  RESULTS
  The ion ratios for each of the dextrose markers at m/z 325, 399 and 473 exhibit linearity with the concentration of the dextrose component of TPN added to blood. The lowest detectable dextrose concentration added to blood was 7.6 mmol/l at 1:80 v/v TPN in blood. Furthermore, the concentrations of amino acids were linear with the concentration of the amino acid component of TPN added to blood. At the lowest detectable concentrations of dextrose marker, the amino acid concentrations were at or above the values considered abnormal in newborn screening laboratories. The molar ratios of amino acids approached the relative quantity of amino acid in the TPN solution with increasing enrichments in blood.
  
  
  CONCLUSIONS
  Detection of the combinations of dextrose markers, very high elevations of amino acids and unusual molar ratios can be used to reject a specimen as improperly collected rather than declaring it a false positive and hence reduce false positive rates. This process enhances efficiency, reduces parental anxiety, and improves positive predictive values.
authors.affiliation: The Pediatrix Center for Research, Education and Quality, Pediatrix Medical Group, Inc., 1301 Concord Terrace, Sunrise, FL 33323, USA. donald_chace@pediatrix.com
authors.forename: Donald H
authors.initials: DH
authors.lastname: Chace
authors.forename: Víctor R
authors.initials: VR
authors.lastname: De Jesús
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Lim
authors.forename: W Harry
authors.initials: WH
authors.lastname: Hannon
authors.forename: Reese H
authors.initials: RH
authors.lastname: Clark
authors.forename: Alan R
authors.initials: AR
authors.lastname: Spitzer
mesh_terms: D000596:Amino Acids / Q000097:blood*; D001800:Blood Specimen Collection; D006801:Humans; D007231:Infant, Newborn; D015997:Neonatal Screening; D010289:Parenteral Nutrition, Total / Q000379:methods*; D012680:Sensitivity and Specificity
chemical_list: D000596:Amino Acids