Age- and Sex-Specific Dynamics in 22 Hematologic and Biochemical Analytes from Birth to Adolescence

2015 ◽  
Vol 61 (7) ◽  
pp. 964-973 ◽  
Author(s):  
Jakob Zierk ◽  
Farhad Arzideh ◽  
Tobias Rechenauer ◽  
Rainer Haeckel ◽  
Wolfgang Rascher ◽  
...  
Keyword(s):  
Cell Count ◽  
Clinical Decision Making ◽  
Clinical Care ◽  
Age Groups ◽  
Reference Intervals ◽  
Interindividual Variation ◽  
Red Cell ◽  
Distribution Width ◽  
Laboratory Test Results ◽  
Age And Sex

Abstract BACKGROUND Pediatric laboratory test results must be interpreted in the context of interindividual variation and age- and sex-dependent dynamics. Reference intervals as presently defined for separate age groups can only approximate the age-related dynamics encountered in pediatrics. Continuous reference intervals from birth to adulthood are not available for most laboratory analytes because of the ethical and practical constraints of defining reference intervals using a population of healthy community children. We applied an indirect method to generate continuous reference intervals for 22 hematologic and biochemical analytes by analyzing clinical laboratory data from blood samples taken during clinical care of patients. METHODS We included samples from 32 000 different inpatients and outpatients (167 000 samples per analyte) from a German pediatric tertiary care center. Measurements were performed on a Sysmex-XE 2100 and a Cobas Integra 800 during clinical care over a 6-year period. The distribution of samples considered normal was estimated with an established indirect statistical approach and used for the calculation of reference intervals. RESULTS We provide continuous reference intervals from birth to adulthood for 9 hematology analytes (hemoglobin, hematocrit, red cell indices, red cell count, red cell distribution width, white cell count, and platelet count) and 13 biochemical analytes (sodium, chloride, potassium, calcium, magnesium, phosphate, creatinine, aspartate transaminase, alanine transaminase, γ-glutamyltransferase, alkaline phosphatase, lactate dehydrogenase, and total protein). CONCLUSIONS Continuous reference intervals capture the population changes in laboratory analytes during pediatric development more accurately than age groups. After local validation, the reference intervals provided should allow a more precise consideration of these dynamics in clinical decision making.

Next-generation reference intervals for pediatric hematology

2019 ◽  
Vol 57 (10) ◽  
pp. 1595-1607 ◽  
Author(s):  
Jakob Zierk ◽  
Johannes Hirschmann ◽  
Dennis Toddenroth ◽  
Farhad Arzideh ◽  
Rainer Haeckel ◽  
...  
Keyword(s):  
Cell Count ◽  
Clinical Decision Making ◽  
Reference Intervals ◽  
Red Cell ◽  
Test Results ◽  
Distribution Width ◽  
Hematological Diseases ◽  
Pediatric Hematology ◽  
Clinical Scenarios ◽  
Z Scores

Abstract Background Interpreting hematology analytes in children is challenging due to the extensive changes in hematopoiesis that accompany physiological development and lead to pronounced sex- and age-specific dynamics. Continuous percentile charts from birth to adulthood allow accurate consideration of these dynamics. However, the ethical and practical challenges unique to pediatric reference intervals have restricted the creation of such percentile charts, and limitations in current approaches to laboratory test result displays restrict their use when guiding clinical decisions. Methods We employed an improved data-driven approach to create percentile charts from laboratory data collected during patient care in 10 German centers (9,576,910 samples from 358,292 patients, 412,905–1,278,987 samples per analyte). We demonstrate visualization of hematology test results using percentile charts and z-scores (www.pedref.org/hematology) and assess the potential of percentiles and z-scores to support diagnosis of different hematological diseases. Results We created percentile charts for hemoglobin, hematocrit, red cell indices, red cell count, red cell distribution width, white cell count and platelet count in girls and boys from birth to 18 years of age. Comparison of pediatricians evaluating complex clinical scenarios using percentile charts versus conventional/tabular representations shows that percentile charts can enhance physician assessment in selected example cases. Age-specific percentiles and z-scores, compared with absolute test results, improve the identification of children with blood count abnormalities and the discrimination between different hematological diseases. Conclusions The provided reference intervals enable precise assessment of pediatric hematology test results. Representation of test results using percentiles and z-scores facilitates their interpretation and demonstrates the potential of digital approaches to improve clinical decision-making.

High-resolution pediatric reference intervals for 15 biochemical analytes described using fractional polynomials

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jakob Zierk ◽  
Hannsjörg Baum ◽  
Alexander Bertram ◽  
Martin Boeker ◽  
Armin Buchwald ◽  
...  
Keyword(s):  
Information Systems ◽  
Laboratory Test ◽  
Clinical Decision Making ◽  
Age Groups ◽  
Clinical Decision ◽  
Reference Intervals ◽  
Test Results ◽  
Laboratory Test Results ◽  
Glutamyl Transferase ◽  
Laboratory Information Systems

Abstract Objectives Assessment of children’s laboratory test results requires consideration of the extensive changes that occur during physiological development and result in pronounced sex- and age-specific dynamics in many biochemical analytes. Pediatric reference intervals have to account for these dynamics, but ethical and practical challenges limit the availability of appropriate pediatric reference intervals that cover children from birth to adulthood. We have therefore initiated the multi-center data-driven PEDREF project (Next-Generation Pediatric Reference Intervals) to create pediatric reference intervals using data from laboratory information systems. Methods We analyzed laboratory test results from 638,683 patients (217,883–982,548 samples per analyte, a median of 603,745 test results per analyte, and 10,298,067 test results in total) performed during patient care in 13 German centers. Test results from children with repeat measurements were discarded, and we estimated the distribution of physiological test results using a validated statistical approach (kosmic). Results We report continuous pediatric reference intervals and percentile charts for alanine transaminase, aspartate transaminase, lactate dehydrogenase, alkaline phosphatase, γ-glutamyl-transferase, total protein, albumin, creatinine, urea, sodium, potassium, calcium, chloride, anorganic phosphate, and magnesium. Reference intervals are provided as tables and fractional polynomial functions (i.e., mathematical equations) that can be integrated into laboratory information systems. Additionally, Z-scores and percentiles enable the normalization of test results by age and sex to facilitate their interpretation across age groups. Conclusions The provided reference intervals and percentile charts enable precise assessment of laboratory test results in children from birth to adulthood. Our findings highlight the pronounced dynamics in many biochemical analytes in neonates, which require particular consideration in reference intervals to support clinical decision making most effectively.

scholarly journals Age- and sex-associated differences in hematology and biochemistry parameters of Dunkin Hartley guinea pigs (Cavia porcellus)

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0253794
Author(s):  
Alexa P. Spittler ◽  
Maryam F. Afzali ◽  
Sydney B. Bork ◽  
Lindsey H. Burton ◽  
Lauren B. Radakovich ◽  
...  
Keyword(s):  
Blood Cell ◽  
Cell Count ◽  
Red Blood Cell ◽  
Guinea Pigs ◽  
Biochemical Parameters ◽  
Hemoglobin Concentration ◽  
Reference Intervals ◽  
Blood Cell Count ◽  
Distribution Width ◽  
Age And Sex

The Dunkin Hartley is the most common guinea pig strain used in biomedical research, particularly for studies of asthma, allergy, infectious disease, reproduction, and osteoarthritis. Minimally invasive blood tests, such as complete blood counts and serum biochemistry profiles, are often collected for diagnostics and laboratory analyses. However, reference intervals for these assays have not yet been well-documented in this strain. The purpose of this study was to establish reference intervals for hematologic and biochemical parameters of Dunkin Hartley guinea pigs and determine age- and sex-related differences. Hematologic and biochemical parameters were retrospectively obtained from 145 male and 68 female guinea pigs between 2 and 15 months of age. All blood parameters were analyzed by a veterinary clinical pathology laboratory. Reference intervals were established according to the American Society for Veterinary Clinical Pathology guidelines. Age- and sex-related differences were determined using unpaired t-tests or nonparametric Mann-Whitney tests. Hematocrit, red blood cell distribution width, mean platelet volume, white blood cell count, heterophils, monocytes, eosinophils, glucose, blood urea nitrogen, creatinine, calcium, magnesium, total protein, albumin, globulin, cholesterol, aspartate aminotransferase, gamma glutamyl transferase, and bicarbonate increased with age. Mean corpuscular hemoglobin concentration, cellular hemoglobin concentration mean, platelets, lymphocytes, phosphorus, albumin/globulin ratio, alkaline phosphatase, anion gap, and calculated osmolality decreased with age. Males had higher hemoglobin, hematocrit, red blood cell count, mean corpuscular hemoglobin concentration, white blood cell count, heterophils, Foa-Kurloff cells, alanine aminotransferase, and bicarbonate and lower mean corpuscular volume, red blood cell distribution width, platelets, mean platelet volume, eosinophils, total protein, albumin, globulin, cholesterol, potassium, anion gap, calculated osmolality, and iron compared to females. Establishing age and sex differences in hematologic and biochemical parameters of Dunkin Hartley guinea pigs provides valuable insight into their physiology to better evaluate diagnostics and experimental results.

scholarly journals Reference intervals for 26 common biochemical analytes in term neonates in Jilin Province, China

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kaijin Wang ◽  
Xuetong Zhu ◽  
Qi Zhou ◽  
Jiancheng Xu
Keyword(s):  
Lactate Dehydrogenase ◽  
Clinical Decision Making ◽  
Reference Intervals ◽  
Individual Characteristics ◽  
Integrated System ◽  
Delivery Mode ◽  
Related Factor ◽  
Term Neonates ◽  
Age Related ◽  
Laboratory Test Results

Abstract Background Biochemical analytes provide information for neonatal disease management and therapy, and population-based reference intervals (RIs) are essential to accurately interpret laboratory test results. This study aimed to establish local RIs for biochemical assays in term neonates. Methods A total of 195 healthy term neonates from birth to 3rd day were recruited as reference individuals prospectively. Analytes of 26 common biochemistries were measured using the VITROS 5600 Integrated System. The 3-level nested ANOVA was performed to assess the need for partitioning RIs of each analyte, and RIs were derived by a nonparametric method or robust method. Multiple regression analysis was used to evaluate specific correlations between the analytes and individual characteristics including age, gender, gestational age, birthweight and delivery mode. Results There were no between-sex differences in all analytes, whereas there were significant between-day-age differences in 6 analytes. Small between-delivery-mode differences were observed in the results for potassium, phosphorus, and urea. The major related factor of most analytes was postnatal age. During the first 3 days, values of iron, lipids and lipoproteins increased; creatinine, urea, uric acid, creatine kinase and lactate dehydrogenase decreased; other analytes showed slight changes or relatively stable trends. Reference limits of some analytes, particularly lactate dehydrogenase and alkaline phosphatase, were significantly different from adult and pediatric groups. Conclusions RIs of 26 common biochemical analytes are established for term neonates aged 0 to 3 days in northeast China. Additionally, it is suggested that age-related changes should be valued in the clinical decision-making process for newborns.

scholarly journals Can red cell distribution width be a new parameter for predicting higher CD34+ cell count in the harvest?

2018 ◽  
Vol 51 (1) ◽  
pp. 47-52
Author(s):  
Eren Gündüz ◽  
Tuba Bulduk ◽  
Hava Üsküdar Teke ◽  
Ahmet Musmul ◽  
Neslihan Andıç
Keyword(s):  
Cell Count ◽  
Red Cell Distribution Width ◽  
Red Cell ◽  
Cell Distribution ◽  
Distribution Width

Mean Platelet Volume, Red Cell Distribution Width, and Complete Blood Cell Count Indices in Retinal Vein Occlusions

2020 ◽  
Vol 28 (1) ◽  
pp. 39-47
Author(s):  
Antonio Pinna ◽  
Tiziana Porcu ◽  
Jacopo Marzano ◽  
Francesco Boscia ◽  
Panagiotis Paliogiannis ◽  
...  
Keyword(s):  
Blood Cell ◽  
Cell Count ◽  
Mean Platelet Volume ◽  
Red Cell ◽  
Cell Distribution ◽  
Complete Blood Cell Count ◽  
Blood Cell Count ◽  
Platelet Volume ◽  
Distribution Width ◽  
Retinal Vein Occlusions

scholarly journals Age- and sex-specific reference intervals for the serum cystatin C/creatinine ratio in healthy children (0–18 years old)

2019 ◽  
Vol 47 (7) ◽  
pp. 3151-3159 ◽  
Author(s):  
Changjin Liu ◽  
Jing Wen ◽  
Jialin Xiang ◽  
Xuhong Ouyang ◽  
Yan Yang ◽  
...  
Keyword(s):  
Cystatin C ◽  
Pediatric Population ◽  
Age Groups ◽  
Serum Markers ◽  
Reference Intervals ◽  
Specific Reference ◽  
Healthy Children ◽  
Serum Samples ◽  
Serum Cystatin C ◽  
Age And Sex

Objective This study aimed to investigate serum levels of the cystatin C (CysC)/creatinine (Cr) ratio and renal serum markers (CysC, Cr, urea, and uric acid [UA]) for different ages and by sex. We also aimed to establish pediatric reference intervals for the serum CysC/Cr ratio. Methods Serum samples were collected from 4765 healthy children (0–18 years old). Serum markers of renal function were measured, and the CysC/Cr ratio of each participant was calculated and statistically analyzed. Results The renal marker CysC did not substantially change after 1 year old. Cr, urea, and UA levels generally increased with age. However, the serum CysC/Cr ratio steadily decreased with age. The CysC/Cr ratio showed significant differences in age among all age groups and varied with sex, except for in the 1 to 6-year-old groups. The overall serum CysC/Cr ratio in girls was higher than that in boys. Conclusion Reference intervals of the serum CysC/Cr ratio in the pediatric population were established. These intervals need to be partitioned by age and sex.

scholarly journals Clinical thresholds for diagnosing iron deficiency: comparison of functional assessment of serum ferritin to population based centiles

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Gorkem Sezgin ◽  
Paul Monagle ◽  
Tze Ping Loh ◽  
Vera Ignjatovic ◽  
Monsurul Hoq ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Serum Ferritin ◽  
Age Groups ◽  
Hemoglobin Concentration ◽  
Population Based ◽  
Reference Intervals ◽  
Deficiency Anemia ◽  
Distribution Width ◽  
Iron Deficient ◽  
Lower Limits

Abstract Low serum ferritin is diagnostic of iron deficiency, yet its published lower cut-off values are highly variable, particularly for pediatric populations. Lower cut-off values are commonly reported as 2.5th percentiles, and is based on the variation of ferritin values in the population. Our objective was to determine whether a functional approach based on iron deficient erythropoiesis could provide a better alternative. Utilizing 64,443 ferritin test results from pediatric electronic health records, we conducted various statistical techniques to derive 2.5th percentiles, and also derived functional reference limits through the association between ferritin and erythrocyte parameters: hemoglobin, mean corpuscular volume, mean cell hemoglobin concentration, and red cell distribution width. We find that lower limits of reference intervals derived as centiles are too low for clinical interpretation. Functional limits indicate iron deficiency anemia starts to occur when ferritin levels reach 10 µg/L, and are largely similar between genders and age groups. In comparison, centiles (2.5%) presented with lower limits overall, with varying levels depending on age and gender. Functionally-derived limits better reflects the underlying physiology of a patient, and may provide a basis for deriving a threshold related to treatment of iron deficiency and any other biomarker with functional outcomes.

scholarly journals Data mining of pediatric reference intervals

2021 ◽  
Vol 45 (6) ◽  
pp. 311-317
Author(s):  
Jakob Zierk ◽  
Markus Metzler ◽  
Manfred Rauh
Keyword(s):  
Data Mining ◽  
Information Systems ◽  
Statistical Methods ◽  
Clinical Decision Making ◽  
Reference Intervals ◽  
Healthy Children ◽  
Test Results ◽  
Young Infants ◽  
Age Related ◽  
Laboratory Test Results

Abstract Laboratory tests are essential to assess the health status and to guide patient care in individuals of all ages. The interpretation of quantitative test results requires availability of appropriate reference intervals, and reference intervals in children have to account for the extensive physiological dynamics with age in many biomarkers. Creation of reference intervals using conventional approaches requires the sampling of healthy individuals, which is opposed by ethical and practical considerations in children, due to the need for a large number of blood samples from healthy children of all ages, including neonates and young infants. This limits the availability and quality of pediatric reference intervals, and ultimately negatively impacts pediatric clinical decision-making. Data mining approaches use laboratory test results and clinical information from hospital information systems to create reference intervals. The extensive number of available test results from laboratory information systems and advanced statistical methods enable the creation of pediatric reference intervals with an unprecedented age-related accuracy for children of all ages. Ongoing developments regarding the availability and standardization of electronic medical records and of indirect statistical methods will further improve the benefit of data mining for pediatric reference intervals.

scholarly journals Verification of reference intervals in routine clinical laboratories: practical challenges and recommendations

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Yesim Ozarda ◽  
Victoria Higgins ◽  
Khosrow Adeli
Keyword(s):  
Clinical Laboratory ◽  
Local Population ◽  
Age Groups ◽  
External Source ◽  
Reference Intervals ◽  
Laboratory Method ◽  
Test Results ◽  
Multicenter Studies ◽  
Clinical Laboratories ◽  
Laboratory Test Results

Abstract Reference intervals (RIs) are fundamental tools used by healthcare and laboratory professionals to interpret patient laboratory test results, ideally enabling differentiation of healthy and unhealthy individuals. Under optimal conditions, a laboratory should perform its own RI study to establish RIs specific for its method and local population. However, the process of developing RIs is often beyond the capabilities of an individual laboratory due to the complex, expensive and time-consuming process to develop them. Therefore, a laboratory can alternatively verify RIs established by an external source. Common RIs can be established by large, multicenter studies and can subsequently be received by local laboratories using various verification procedures. The standard approach to verify RIs recommended by the Clinical Laboratory Standards Institute (CLSI) EP28-A3c guideline for routine clinical laboratories is to collect and analyze a minimum of 20 samples from healthy subjects from the local population. Alternatively, “data mining” techniques using large amounts of patient test results can be used to verify RIs, considering both the laboratory method and local population. Although procedures for verifying RIs in the literature and guidelines are clear in theory, gaps remain for the implementation of these procedures in routine clinical laboratories. Pediatric and geriatric age-groups also continue to pose additional challenges in respect of acquiring and verifying RIs. In this article, we review the current guidelines/approaches and challenges to RI verification and provide a practical guide for routine implementation in clinical laboratories.

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