Association Between Median Household Income and Perioperative Outcomes of Lumbar Spinal Fusion: An Analysis of the National Inpatient Sample (2009-2020).

BACKGROUND: Relationships between low socioeconomic status (SES) and surgical outcomes are well established for certain procedures. However, scant literature has focused on relationships between median household income and lumbar fusion outcomes. METHODS: Patients who underwent fusion procedures between January 1, 2009 and December 31, 2020 were identified from the National Inpatient Sample (NIS) database. They were categorized into 4 quartiles, from lowest to highest, based on median household incomes in respective zip codes. We applied univariable and multivariable linear and logistic regression models to analyze perioperative data according to income quartiles. RESULTS: We included 2,826,396 patients. In multivariable regression, patients in the 3 lowest income quartiles exhibited higher rates of in-hospital cardiac events perioperatively, with odds ratios (OR) of 1.19 (95% confidence interval[CI]1.13-1.26, p<0.001), 1.10 (95%CI 1.05-1.16, p<0.001), and 1.06 (95%CI 1.01-1.12, p=0.011) for the first, second, and third quartiles, respectively. Patients in the lowest income (first) quartile had a higher occurrence of perioperative urinary complications (OR=1.07, 95%CI 1.03-1.12, p=0.001), systemic infectious complications (OR=1.17, 95% CI 1.04-1.32, p=0.006), neurological deficit (OR=1.17, 95%CI 1.06-1.30, p=0.002), and wound infections (OR=1.22, 95%CI 1.12-1.34, p<0.001). Those in the 3 lowest income quartiles were less likely to experience respiratory, gastrointestinal, and venous thrombotic complications (p<0.05). The lowest income quartile had protective associations for dural tears (OR 0.93, 95%CI 0.89-0.99, p=0.038) and postprocedure anemia across all 3 lower quartiles, with OR<1 and p<0.001. CONCLUSION: Reduced household income significantly affected perioperative outcomes after lumbar fusion and should be taken into consideration during the perioperative period.

Correlations Between Psychiatric Disorders and Perioperative Outcomes after Lumbar Fusions: An Analysis of the National Inpatient Sample (2009-2020).

BACKGROUND: Preoperative diagnoses of psychiatric disorders have a demonstrated association with higher rates of perioperative complications. However, recent studies examining the influence of psychiatric disorders on lumbar fusion outcomes are scarce. Our objective was to determine the relationship between the most common psychiatric disorders and perioperative outcomes after lumbar fusion. METHODS: Demographic and perioperative data for patients who underwent lumbar spine fusion between 2009 and 2020 were collected from the National Inpatient Sample (NIS) database. These patients were divided into two groups: those who were previously diagnosed with depression, bipolar disorder, or anxiety, and those who were not. Univariable and multivariable linear and logistic regression models were utilized to analyze the data. RESULTS: Of 2,877,241 patients identified in the NIS database as having undergone lumbar fusion, 647,951 had diagnosed psychiatric disorders, and the remaining 2,229,290 were the unaffected cohort. On multivariable analysis, patients diagnosed with psychiatric disorders had significantly increased odds of respiratory (odds ratio [OR]:1.09) and urinary (OR:1.08) complications, and experienced higher odds of mechanical injury (OR:1.27), fusion disorders (OR:1.62), dural tears (OR:1.08), postprocedure anemia (OR:1.29), longer hospital stays, and higher total costs, (p<0.001). Conversely, patients with psychiatric disorders had lower odds of neurologic injury (OR:0.8) and wound complications (OR:0.91) (p<0.05). CONCLUSION: Patients with depression, bipolar disorder, or anxiety exhibited higher rates of certain types of complications. However, they appeared to have fewer neurological injuries and wound complications than patients without these psychiatric disorders. These findings highlight the necessity for additional studies to elucidate underlying reasons for these disparities.

Comparative analysis of patient demographics, perioperative outcomes, and adverse events after lumbar spinal fusion between urban and rural hospitals: an analysis of the National Inpatient Sample (NIS) database.

OBJECTIVE: Rural location of a patient's primary residence has been associated with worse clinical and surgical outcomes due to limited resource availability in these parts of the US. However, there is a paucity of literature investigating the effect that a rural hospital location may have on these outcomes specific to lumbar spine fusions. METHODS: Using the National Inpatient Sample (NIS) database, we identified all patients who underwent primary lumbar spinal fusion in the years between 2009 and 2020. Patients were separated according to whether the operative hospital was considered rural or urban. Univariable and multivariable regression models were used for data analysis. RESULTS: Of 2,863,816 patients identified, 120,298 (4.2 %) had their operation at a rural hospital, with the remaining in an urban hospital. Patients in the urban cohort were younger (P < .001), more likely to have private insurance (39.81 % vs 31.95 %, P < .001), and fewer of them were in the first (22.52 % vs 43.00 %, P < .001) and second (25.96 % vs 38.90 %, P < .001) quartiles of median household income compared to the rural cohort. The urban cohort had significantly increased rates of respiratory (4.49 % vs 3.37 %), urinary (5.25 % vs 4.15 %), infectious (0.49 % vs 0.32 %), venous thrombotic (0.57 % vs 0.24 %, P < .001), and neurological (0.79 % vs 0.36 %) (all P < .001) perioperative complications. On multivariable analysis, the urban cohort had significantly increased odds of the same perioperative complications: respiratory (odds ratio[OR] = 1.48; 95 % confidence interval [CI], 1.26-1.74), urinary (OR = 1.34; 95 %CI, 1.20-1.50), infection (OR = 1.63; 95 %CI, 1.23-2.17), venous thrombotic (OR = 1.79; 95 %CI, 1.32-2.41), neurological injury (OR = 1.92; 95 %CI, 1.46-2.53), and localized infection (OR = 1.65; 95 %CI, 1.25-2.17) (all P < .001). CONCLUSIONS: Patients undergoing lumbar fusions experience significantly different outcomes based on the rural or urban location of the operative hospital.

Single newborn screen or routine second screening for primary congenital hypothyroidism.

Routine second screening of most newborns at 8-14 days of life for a panel of newborn conditions occurs in 12 U.S. states, while newborns in the other states typically undergo only a single routine newborn screen. The study objective was to evaluate screening consequences for primary congenital hypothyroidism (CH) in one- and two-screen states according to laboratory practices and medical or biochemical characteristics of screen-positive cases. Individual-level medical and biochemical data were retrospectively collected and analyzed for 2251 primary CH cases in one-screen (CA, WI) and two-screen (AL, DE, MD, OR, TX) states. Aggregate data were collected and analyzed for medical and biochemical characteristics of all screened newborns in the states. Among the states evaluated in this study, the detection rate of primary CH was higher in the one-screen states. In the two-screen states, 11.5% of cases were detected on the second screen. In multivariate analyses, only race/ethnicity was a significant predictor of cases identified on the first versus second screen, which likely reflects a physiologic difference in primary CH presentation. Newborn screening programs must heed the potential for newborns with CH not being detected by a single screen, particularly newborns of certain races/ethnicities. If the two-screen states converted to a single screen using their current algorithms, newborns currently identified on the routine second screen would presumably not be detected, resulting in probable delayed diagnosis and treatment. However, based on the one-screen state experiences, with appropriate modifications in screening method and algorithm, the two-screen states might convert to single screen operation for CH without loss in performance.

Congenital adrenal hyperplasia cases identified by newborn screening in one- and two-screen states.

There is no clear consensus among state newborn screening programs on whether routine second screening of newborns identifies clinically relevant cases of congenital adrenal hyperplasia. This retrospective study evaluated laboratory practices, along with biochemical and medical characteristics of congenital adrenal hyperplasia (CAH) cases (1) detected on the first newborn screen in one-screen compared to two-screen states, and (2) detected on the first versus the second screen in the two-screen states, to determine the effectiveness of a second screen. A total of 374 confirmed cases of CAH from 2 one-screen states and 5 two-screen states were included in this study. Demographic data and diagnostic information on each reported case were collected and analyzed. Additionally, laboratory data, including screening methodologies and algorithms, were evaluated. The one-screen states reported 99 cases of CAH out of 1,740,586 (1 in 17,500) newborns screened: 88 (89%) identified on the first screen and 5 (5%) identified on the targeted second screen. The two-screen states reported 275 cases of CAH out of 2,629,627 (1 in 9500) newborns screened: 165 (60%) identified on the first screen and 99 (36%) identified on the second screen. Using a multivariate model, the only significant predictor of whether a case was identified on the first or the second screen in the two-screen states was the type of CAH. Compared with classical salt-wasting CAH, classical simple virilizing and non-classical CAH cases were less likely to be detected on the first versus the second screen. The routine second newborn screen is important for identifying children with CAH, particularly simple virilizing and non-classical forms, which might otherwise not be captured through a single screen.

Newborn blood spot screening test using multiplexed real-time PCR to simultaneously screen for spinal muscular atrophy and severe combined immunodeficiency.

BACKGROUND: Spinal muscular atrophy (SMA) is a motor neuron disorder caused by the absence of a functional survival of motor neuron 1, telomeric (SMN1) gene. Type I SMA, a lethal disease of infancy, accounts for the majority of cases. Newborn blood spot screening (NBS) to detect severe combined immunodeficiency (SCID) has been implemented in public health laboratories in the last 5 years. SCID detection is based on real-time PCR assays to measure T-cell receptor excision circles (TREC), a byproduct of T-cell development. We modified a multiplexed real-time PCR TREC assay to simultaneously determine the presence or absence of the SMN1 gene from a dried blood spot (DBS) punch in a single reaction well. METHOD: An SMN1 assay using a locked nucleic acid probe was initially developed with cell culture and umbilical cord blood (UCB) DNA extracts, and then integrated into the TREC assay. DBS punches were placed in 96-well arrays, washed, and amplified directly using reagents specific for TREC, a reference gene [ribonuclease P/MRP 30kDa subunit (RPP30)], and the SMN1 gene. The assay was tested on DBS made from UCB units and from peripheral blood samples of SMA-affected individuals and their family members. RESULTS: DBS made from SMA-affected individuals showed no SMN1-specific amplification, whereas DBS made from all unaffected carriers and UCB showed SMN1 amplification above a well-defined threshold. TREC and RPP30 content in all DBS were within the age-adjusted expected range. CONCLUSIONS: SMA caused by the absence of SMN1 can be detected from the same DBS punch used to screen newborns for SCID.

Performance of succinylacetone assays and their associated proficiency testing outcomes.

BACKGROUND: Succinylacetone (SUAC) is the primary metabolic marker for hepatorenal tyrosinemia. MATERIALS AND METHODS: We used results reported for dried-blood-spot proficiency testing (PT) specimens and hepatorenal tyrosinemia patients' newborn screening (NBS) samples to demonstrate analytic biases in SUAC recoveries and differences in presumptive clinical classifications. RESULTS: SUAC recoveries from non-kit and NeoBase™ kit tandem mass spectrometry methods were markedly different. Kit users that set high cutoff values submitted discordant clinical assessments of "within normal limits" for PT specimens enriched with 10-15 µmol SUAC/L in blood. SUAC levels in tyrosinemia patients' NBS samples analyzed by NeoBase™ kit were lower than those in samples analyzed by non-kit methods. CONCLUSIONS: From 2009 to 2011, analytic biases in SUAC recoveries were consistent. Discordant clinical assessments of PT specimens were associated with high cutoff values for NeoBase™ kit results. Method-related differences in SUAC concentrations of tyrosinemia patients' samples were consistent with those of PT specimens.

Immunoreactive Trypsinogen (IRT) as a Biomarker for Cystic Fibrosis: challenges in newborn dried blood spot screening.

On May 23-24, 2011, a workshop entitled "Immunoreactive Trypsinogen (IRT) as a Biomarker for Cystic Fibrosis: Technical Issues and Challenges" was held in Annapolis, Maryland. The two-day workshop was co-hosted by the National Newborn Screening and Genetics Resource Center, Austin, Texas, and the Association of Public Health Laboratories, Silver Spring, Maryland, in collaboration with the Health Resources and Services Administration and the Centers for Disease Control and Prevention. Participants included nearly 40 representatives from U.S. state public health and commercial laboratories performing newborn dried blood spot screening tests for cystic fibrosis (CF), the federal government, academic research institutions, and commercial vendors of products used in newborn screening. Representatives from selected European CF newborn screening programs were also present. The workshop focused on identifying key IRT testing issues and mechanisms for achieving their resolution and laboratory harmonization in order to reduce, or eliminate completely, the late identified CF cases following a negative newborn screen. Informative findings are reported, their impacts on improving IRT screening are described, and their implications are discussed.

CFTR mutation analysis and haplotype associations in CF patients.

Most newborn screening (NBS) laboratories use second-tier molecular tests for cystic fibrosis (CF) using dried blood spots (DBS). The Centers for Disease Control and Prevention's NBS Quality Assurance Program offers proficiency testing (PT) in DBS for CF transmembrane conductance regulator (CFTR) gene mutation detection. Extensive molecular characterization on 76 CF patients, family members or screen positive newborns was performed for quality assurance. The coding, regulatory regions and portions of all introns were sequenced and large insertions/deletions were characterized as well as two intronic di-nucleotide microsatellites. For CF patient samples, at least two mutations were identified/verified and four specimens contained three likely CF-associated mutations. Thirty-four sequence variations in 152 chromosomes were identified, five of which were not previously reported. Twenty-seven of these variants were used to predict haplotypes from the major haplotype block defined by HapMap data that spans the promoter through intron 19. Chromosomes containing the F508del (p.Phe508del), G542X (p.Gly542X) and N1303K (p.Asn1303Lys) mutations shared a common haplotype subgroup, consistent with a common ancient European founder. Understanding the haplotype background of CF-associated mutations in the U.S. population provides a framework for future phenotype/genotype studies and will assist in determining a likely cis/trans phase of the mutations without need for parent studies.

The stability of markers in dried-blood spots for recommended newborn screening disorders in the United States.

OBJECTIVE: We aimed to measure separately the contributions of heat and humidity to changes in levels of 34 markers of inborn disorders in dried-blood-spot (DBS) samples. DESIGN AND METHODS: We stored paired sets of DBSs at 37°C for predetermined intervals in low-humidity and high-humidity environments. Marker levels of all samples in each complete sample set were measured in a single analytic run. RESULTS: During the 30 ± 5 day studies, galactose-1-phosphate uridyltransferase and biotinidase lost almost 65% of initial activities in low-humidity storage; most of the degradation in 27 other markers was attributable to adverse effects of high-humidity storage; seven markers in DBSs stored at high humidity lost more than 90% of initial levels by the end of the study and 4 of the 7 lost more than 50% of initial levels within the first week of storage. CONCLUSIONS: Minimizing both humidity and temperature in DBS transportation and storage environments is essential to maintaining sample integrity.

Committee report: Considerations and recommendations for national guidance regarding the retention and use of residual dried blood spot specimens after newborn screening.

Newborn screening programs are state based with variable policies. Guidance regarding the retention, storage, and use of portions of newborn screening dried blood spots that remain after screening (residual specimens) was first published in 1996. Since then, newborn screening programs have paid increased attention to specimen storage and usage issues. Standard residual specimen uses include quality assurance and program evaluation, treatment efficacy, test refinement, and result verification. In all cases, privacy and security are primary concerns. In general, two distinct state practices regarding the storage and use of residual newborn screening specimens exist: (1) short-term storage (<3 years), primarily for standard program uses and (2) long-term storage (>18 years), for standard program uses and possible important public health research uses. Recently, there have been concerns in some consumer communities regarding both the potential uses of residual specimens and patient (newborn and family) privacy. To assist in policy improvements that can protect the individual's privacy and allow for important public health uses of residual newborn screening specimens, the Secretary of Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children has developed recommendations (with requested action by the Secretary where applicable). This report presents the Committee's recommendations and reviews the pertinent associated issues.

Detection of TPN contamination of dried blood spots used in newborn and metabolic screening and its impact on quantitative measurement of amino acids.

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.

Implementation of the first worldwide quality assurance program for cystic fibrosis multiple mutation detection in population-based screening.

BACKGROUND: CDC's Newborn Screening Quality Assurance Program collaborated with several U.S. Cystic Fibrosis Care Centers to collect specimens for development of a molecular CFTR proficiency testing program using dried-blood spots for newborn screening laboratories. METHODS: Adult and adolescent patients or carriers donated whole blood that was aliquoted onto filter paper cards. Five blind-coded specimens were sent to participating newborn screening laboratories quarterly. Proficiency testing results were evaluated based on presumptive clinical assessment. Individual evaluations and summary reports were sent to each participating laboratory and technical consultations were offered if incorrect assessments were reported. RESULTS: The current CDC repository contains specimens with 39 different CFTR mutations. Up to 45 laboratories have participated in the program. Three years of data showed that correct assessments were reported 97.7% of the time overall when both mutations could be determined. Incorrect assessments that could have lead to a missed case occurred 0.9% of the time, and no information was reported 1.1% of the time due to sample failure. CONCLUSIONS: Results show that laboratories using molecular assays to detect CFTR mutations are performing satisfactorily. The programmatic results presented demonstrate the importance and complexity of providing proficiency testing for DNA-based assays.

The preparation and storage of dried-blood spot quality control materials for lysosomal storage disease screening tests.

OBJECTIVE: We aimed to prepare dried-blood spot (DBS) quality control (QC) materials for lysosomal storage disease (LSD) screening tests and to determine optimum blood and DBS storage conditions. METHODS: We compared enzyme activities of five LSD markers in adult blood, umbilical-cord blood, and leukocyte-reduced blood. We measured activities in liquid blood and DBSs after predetermined intervals at controlled temperatures and humidities. RESULTS: Lysosomal-enzyme activity levels in umbilical-cord blood mimicked those in newborn screening samples. Lysosomal-enzyme activities in leukocyte-reduced blood were lower than in LSD-positive patient samples. Enzyme activities were stable in refrigerated liquid blood for 32 days and in frozen DBSs stored at low humidity for a year. Activity losses from DBSs after 34 days at 37±1°C were 35%-66% in low humidity and 61%-100% in high humidity. CONCLUSIONS: Umbilical-cord blood is the preferred matrix for LSD-normal DBS QC materials. Leukocyte-reduced blood is lysosomal enzyme-deficient. Failure to control humidity during DBS storage results in loss of lysosomal-enzyme activities.

Proficiency testing outcomes of 3-hydroxyisovalerylcarnitine measurements by tandem mass spectrometry in newborn screening.

BACKGROUND: The use of tandem mass spectrometry (MS/MS) for the analysis of amino acids and acylcarnitines from dried-blood spots (DBS) has become routine practice in newborn screening laboratories. The Newborn Screening Quality Assurance Program (NSQAP) added 3-hydroxyisovalerylcarnitine (C5OH) into its routine quality control and proficiency testing (PT) DBS materials for MS/MS to assure the quality of C5OH screening. We report the results from NSQAP evaluations for C5OH-enriched DBS, and summarize participant screening practices based on their analytical methods. METHODS: NSQAP prepared C5OH-enriched DBS materials for its participants. Laboratories reported quantitative and qualitative results. Bias plots of quantitative results were constructed using reported data and the results were sorted by an analytical method. RESULTS: NSQAP participants reported PT specimen 3964 as outside of normal limits for C5OH. The mean C5OH value for derivatized and non-derivatized methods was 2.80 and 2.67 µmol/l, respectively. Reported data from other specimens showed a similar trend in derivatized vs. non-derivatized assay results. Differences in C5OH quantitative values were observed among laboratories using different internal standards. CONCLUSIONS: C5OH MS/MS measurements in DBS assays varied by method and the choice of internal standards. The use of NSQAP's DBS materials allows harmonization of C5OH measurements by newborn screening laboratories worldwide.

Effect of specimen storage conditions on newborn dried blood spots used to assess Toxoplasma gondii immunoglobulin M (IgM).

BACKGROUND: Newborn screening programs store-under varying conditions-residual dried blood spots (DBS). Residual DBS were used to investigate the contribution of congenital infection with Toxoplasma gondii to the etiology of hydrocephalus and as a key step, we assessed the effect of storage conditions on the stability of newborn screening biomarkers. METHODS: Infants with hydrocephalus (410 cases) were identified using population-based birth defects surveillance systems in California, North Carolina, and Texas. Infants without birth defects (448 controls) were randomly selected from the same geographic areas and time periods. California stores DBS with controlled temperature, while North Carolina and Texas store DBS under ambient conditions. After removal of personal identifiers, DBS were tested for Toxo-specific immunoglobulin-M (Toxo-IgM). Because of poor elution of DBS stored in ambient conditions, additional biomarkers were tested on a specimen subset. RESULTS: Among 858 DBS tested, Toxo-IgM was found in 3 cases and no controls from California (N=515) and in no specimens from North Carolina or Texas (N=343). Among the 98 specimens tested for selected biomarkers, statistically significant differences were found for California vs. combined North Carolina and Texas DBS (thyroid stimulating hormone, phenylalanine, methionine, leucine and citrulline p<0.0001; tyrosine and valine p<0.001). CONCLUSIONS: Storage conditions for residual DBS had an effect on the ability to extract, recover, and accurately measure Toxo-IgM and other biomarkers from the filter paper matrix.

Performance properties of filter paper devices for whole blood collection.

BACKGROUND: The Newborn Screening Quality Assurance Program at the Centers for Disease Control and Prevention assesses the adherence to established performance standards of manufactured lots of whole blood filter paper collection devices that are registered by the US FDA. We examined 26 newborn screening analytes measured from blood applied to filter papers from two FDA-cleared sources, Whatman(®) Grade 903 and Ahlstrom Grade 226. The dried blood spots contained analytes at both single levels and dose-response series. RESULTS: We observed overlap at one standard deviation for each analyte, with no more than 4-5% difference between the papers. CONCLUSION: The data demonstrated similarities of analyte recovery between the papers, indicating comparability of the devices for newborn screening and other applications.

Tandem mass spectrometric identification of dextrose markers in dried-blood spots from infants receiving total parenteral nutrition.

BACKGROUND: The false positive rate for the newborn screening of disorders of amino acid metabolism for premature infants is higher than full term infants. This may be due to very low birth weight infants receiving high concentrations of amino acids from total parenteral nutrition (TPN) administration and/or immature metabolism. An investigation of the possible influence of TPN on screening of premature infants resulted in the detection of three unusual peaks in the tandem mass spectrometry (MS/MS) acylcarnitine profile. These markers were closely correlated with the detection of very high multiple amino acid increases in the profiles of newborns administered with TPN and who were ultimately found to be normal and free of inherited metabolic disorders. METHODS: TPN solutions contain a concentrated mixture of amino acids and dextrose and other nutrients in saline. Due to its high concentration and suggestion of a carbohydrate, it was hypothesized that dextrose (D-glucose) was the contaminant and source of the markers detected. Dextrose, stable isotope-labeled 13C6-dextrose and various TPN solutions were analyzed directly or after enrichment in whole blood by multiple MS/MS acquisition modes including MS-only, product and precursor ion and neutral loss scans. RESULTS: Analysis of dried-blood spots (DBS) prepared from whole blood spiked with TPN solutions containing 12.5% dextrose and amino acid formulations designed to deliver 2.5 gm/kg/day of an amino acid mixture had moderate increases of all 3 dextrose markers detected at m/z 325, 399 and 473 as compared to controls. MS-only scans, product and precursor ion scans of dextrose and 13C6-dextrose in positive ion mode confirmed that these 3 peaks are derived from dextrose. Mass spectral analysis of labeled and unlabeled dextrose suggested that these peaks were dimers derived from dextrose. CONCLUSION: The identification of dextrose markers in DBS indicates that high concentrations of dextrose were present in blood and the likely source was contamination by TPN solutions most likely occurring during a sample collection process.