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Indirect determination of pediatric blood count reference intervals
Jakob Zierk1, Farhad Arzideh, Rainer Haeckel
1Department of Pediatrics, University of Erlangen-Nuremberg, Erlangen, Germany.
Insights
This study developed a new indirect method to create continuous pediatric reference intervals (RIs) for laboratory tests, improving accuracy and applicability for children of all ages.
Area of Science:
- Clinical Laboratory Science
- Pediatric Laboratory Medicine
- Biostatistics
Background:
- Establishing pediatric reference intervals (RIs) for laboratory tests is challenging due to age-related variations and difficulties in sampling healthy children.
- Current RIs often rely on small sample sizes and arbitrary age groupings.
- Intra-laboratory RIs tailored to specific populations and analytical devices are not widely adopted.
Purpose of the Study:
- To develop continuous, age-dependent pediatric reference intervals (RIs) for blood count and sodium levels.
- To utilize a large clinical laboratory database for deriving these RIs.
- To address limitations of traditional RI determination methods.
Main Methods:
- A refined indirect approach was employed using a dataset of 60,000 individual samples.
- Samples were stratified by age, and a density function estimated the proportion of healthy samples.
- Continuous RIs were generated by merging age-specific results.
Main Results:
- Continuous, age-dependent RIs were successfully generated for pediatric blood counts and sodium.
- The derived RIs demonstrated high concordance with established laboratory instruments and conventional methods.
- Age-dependent dynamics of reference limits were accurately captured.
Conclusions:
- The indirect method is effective for creating continuous, intra-laboratory RIs from clinical databases.
- Generated RIs are comparable to those from established methods, offering a viable alternative.
- This approach is transferable to other laboratory quantities, especially where conventional methods are limited.
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.
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