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.

Poor reproducibility of IGT and IFG classification suggests caution should be exercised when interpreting a single test result.

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.

Background: Determination of pediatric reference intervals (RIs) for laboratory quantities, including hematological quantities, is complex. The measured quantities vary by age, and obtaining samples from healthy children is difficult. Many widely used RIs are derived from small sample numbers and are split into arbitrary discrete age intervals. Use of intra-laboratory RIs specific to the examined population and analytical device used is not yet fully established. Indirect methods address these issues by deriving RIs from clinical laboratory databases which contain large datasets of both healthy and pathological samples. Methods: A refined indirect approach was used to create continuous age-dependent RIs for blood count quantities and sodium from birth to adulthood. The dataset for each quantity consisted of 60,000 individual samples from our clinical laboratory. Patient samples were separated according to age, and a density function of the proportion of healthy samples was estimated for each age group. The resulting RIs were merged to obtain continuous RIs from birth to adulthood. Results: The obtained RIs were compared to RIs generated by identical laboratory instruments, and to population-specific RIs created using conventional methods. This comparison showed a high concordance of reference limits and their age-dependent dynamics. Conclusions: The indirect approach reported here is well-suited to create continuous, intra-laboratory RIs from clinical laboratory databases and showed that the RIs generated are comparable to those created using established methods. The procedure can be transferred to other laboratory quantities and can be used as an alternative method for RI determination where conventional approaches are limited.

Background: Interpretation of alkaline phosphatase activity in children is challenging due to extensive changes with growth and puberty leading to distinct sex-and age-specific dynamics. Continuous percentile charts from birth to adulthood allow accurate consideration of these dynamics and seem reasonable for an analyte as closely linked to growth as alkaline phosphatase. However, the ethical and practical challenges unique to pediatric reference