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

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.

Establishment of reference intervals for complete blood count parameters in venous blood for children in the Xiamen area, China

“…The WBC count in infants and toddlers were significantly higher than that in older children or adults. With increasing age, the WBC count gradually decreased, and the RI shifted downward in children, consistent with the pattern found in a previous study . The change trend in LY# was very similar to that of WBCs, while that of NE# was the opposite.…”

Establishment of complete blood count reference intervals for Chinese preschoolers

“…These differences presumably are due to the size of the survey area, the number and selection of subjects, hereditary differences, aging, and also inspection systems. RBC, RDW-SD (both P<.01) and HCT, MCHC, PLT (all P<.05) more parameters started to show significant gender differences after 6 months and 2 years old, which may be regarded as onset of age-and sex-specific dynamics concluded by Zierk et al 15 . Physical development (height and weight) change with each passing month before 6 years.…”

Pediatric reference intervals for alkaline phosphatase

“…To ensure valid reference intervals when using indirect procedures, great care must be taken in the selection of samples and statistical algorithms. Previous evaluations of the applied algorithm [6,27] and comparison of our results to reference intervals from CALIPER, created using a direct method [11]. The x-axes are scaled differently on the left-and right-hand side of the figure to account for the dynamics in young infants; the x-axis on the right-hand side starts at 61 days.…”

“…Percentile charts were calculated with an indirect algorithm which we have described and validated previously [6,27]. The method extracts samples of healthy individuals from an input data set, containing both non-pathologic and pathologic samples.…”

“…Continuous classification of test results with percentile charts from birth to adulthood can improve the usefulness of alkaline phosphatase activity as a screening marker for hypophosphatasia and related conditions. In a recent study -based on a data-mining approach using a single center's laboratory data -we demonstrated the complex pattern of change in alkaline phosphatase activity over time, with a high accuracy of age-and sexdependent changes in infancy and puberty [6]. However, representation of the extensive dynamics after birth in neonates (0-28 days) with a high age-specific accuracy, and the creation of percentile charts require analysis of a more comprehensive data set.…”