Indirectly determined hematology reference intervals for pediatric patients in Berlin and Brandenburg

Objectives Establishing direct reference intervals (RIs) for pediatric patients is a very challenging endeavor. Indirectly determined RIs can address this problem by utilization of existing clinical laboratory databases. In order to provide better laboratory services to the local pediatric population, we established population-specific hematology RIs via data mining. Methods Our laboratory information system (LIS) was searched for pediatric blood counts of patients aged from 0 days to 18 years, performed from 1st of January 2018 until 31st of March 2021. In total, 27,554 blood counts on our SYSMEX XN-9000 were initially identified. After application of pre-defined exclusion criteria, 18,531 sample sets remained. Age- and sex-specific RIs were established in accordance with International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and Clinical & Laboratory Standards Institute (CLSI) recommendations. Results When compared to pediatric RIs supplied by other authors, the RIs determined specifically for pediatric patients from Berlin and Brandenburg showed several relevant differences, especially with regard to white blood cell counts (WBCs), red blood cell counts (RBCs), red cell distribution widths (RDW) and platelet counts (PLTs) within the distinct age groups. Additionally, alterations to several published age-specific partitions had to be made, while new sex-specific partitions were introduced for WBCs and PLTs. Conclusions Generic RIs from textbooks, manufacturer information and medical publications – even from nationwide or multicenter studies – commonly used in many laboratories might not reflect the specifics of local patient populations properly. RIs should be tailored to the serviced patient population whenever possible. Careful data mining appears to be suitable for this task.

Establishing laboratory-specific reference intervals for TSH and fT4 by use of the indirect Hoffman method

Background The results of examinations of laboratory parameters are the basis of appropriate medical decisions. The availability of reliable and accurate reference intervals (RIs) for each laboratory parameter is an integral part of its appropriate interpretation. Each medical laboratory should confirm their RIs. Up-to-date reference intervals for thyroid function hormones are still a matter of ongoing controversy. The aim of the study was the application of the indirect Hoffman method to determine RIs for TSH and fT4 based on the large data pools stored in laboratory information systems and the comparison of these RIs to generally used RIs. Material and methods The TSH and fT4 routine examination results of hospitalized and outpatient populations were collected over five years (2015–2019), and reference limits were established by the improved Hoffmann method after the exclusion of outliers. Comparative verification of established RIs was conducted with the RIs values provided by test manufacturers and literature data. Results Various RIs were observed in different age groups in the examined populations. For TSH, RIs varied between different age groups, with a narrower range of RIs in the studied adult population and a shift of both reference boundaries toward higher values in comparison to manufacturers’ data among children. RIs estimated for fT4 were very similar to the manufacturer and literature data. Conclusion Thyroid hormone levels change during a person’s lifetime and vary between sexes, but this difference does not always influence the clinical interpretation of laboratory results in the context of RIs. The use of indirect methods is justified due to the ease and low cost of their application.

Age- and sex-specific pediatric LMS-Percentiles for Laboratory Parameters enabled by Data mining

Background:Various laboratory parameters routinely measured in pediatric practice covariate with sex and age. Conventional reference intervals are not suitable to account for this variation. Here we demonstrate construction of continuous LMS percentile curves from routine laboratory data. This allows adequate adjustment for both sex- and age-dependent covariation in childhood.Material and Methods:Anonymized routine blood test results requested by primary health care physicians were collected, outliers excluded and LMS-models generated in R.Results:Percentiles for several biomarkers derived from a regional population were established in the 'LMS' framework and provided here for comparison with etablished reference ranges, discussion and, potentially, clinical use.Conclusion: The reference framework 'LMS' is well-known from pediatric growth charts and can also be used in laboratory medicine.

Cord-blood derived chemistry reference values in preterm infants for sodium, chloride, potassium, glucose, and creatinine

Objectives: Guidelines recommend preterm infants be supported to maintain their serum electrolytes within “normal” ranges. In term babies, cord blood values differed in pathological pregnancies from healthy ones. Study design: We examined cord blood sodium, chloride, potassium, glucose, and creatinine to derive maturity-related reference intervals. We examined associations with gestational age, delivery mode, singleton versus multiple, and prenatal maternal adverse conditions. We compared preterm cord values to term, and to adult reference ranges. Results: There were 591 infants, 537 preterm and 54 term. Preterm cord glucose levels were steady (3.7+/-1.1mmol/l), while sodium, chloride and creatinine increased over GA by 0.17, 0.14 and 1.07 micromol/week respectively (p<0.003). Average preterm cord potassium and chloride were higher than term (p<0.05). Compared to adult reference intervals, cord preterm reference intervals were higher for chloride (100-111 vs 98-106 mmol/l), lower for creatinine (29-84 vs 62-115 micromol/l), more variable for potassium (2.7-7.9 vs. 3.5-5.0 mmol/l) and sodium (130-141 vs. 136-145 mmol/l). Cesarean section was associated with higher potassium and lower glucose; multiple births with higher chloride and creatinine and lower glucose; SGA with lower glucose. Conclusions: Cord blood values vary across the GA range with increases in sodium, chloride and creatinine while glucose remained steady. Average preterm reference values were higher than term values for potassium and chloride. Preterm reference values differed from published adults’ reference values. The varies across GA and by delivery mode, SGA, and being a multiple, which may have direct implications for neonatal care and fluid management.

Factors Affecting Hematologic and Serum Biochemical Parameters in Healthy Common Marmosets (Callithrix jacchus)

Physiologic changes during development, aging, and pregnancy may affect clinical parameters. Previously available reference values have been based on samples that may include wild and captive marmosets, with little representation of geriatricor pregnant animals. Establishing reference values under various conditions would support better recognition of pathologic conditions in marmosets. One hundred and forty-seven (70 males and 77 females) healthy marmosets from a research colony were included in this study. Exclusion criteria were abnormal physical exam findings at the time of blood sampling, chronicmedications, or clinical or pathologic evidence of disease. Reference intervals were calculated for serum chemistry andhematology. Using metadata, samples were classified based on age, sex, colony source and pregnancy status. Multiple testsindicated significant differences with varying effect sizes, indicating that developing reference intervals based on metadatacan be useful. Across all the comparisons, medium or large effect sizes were observed most frequently in blood urea nitrogen (BUN), calcium, total protein, alkaline phosphatase (ALP), weight and serum albumin. We report normative clinical pathologic data for captive common marmosets through all life stages and reproductive status. Significant differences were observed in most parameters when stratifying data based on age, sex, colony source, or pregnancy, suggesting that developing reference intervals considering this information is important for clinicians.