Age-dependent Changes of Total and Differential White Blood Cell Counts in Children
The complete blood count (CBC) is one of the most frequently used laboratory tests in clinical practice. It plays a crucial role in the diagnostic evaluation of suspected diseases and in wellness screening programs. Among the various components of the CBC, white blood cell (WBC) counts and their differentials, including monocyte count (MONO#), lymphocyte count (LYMPH#), neutrophil count (NEUT#), eosinophil count (EO#), and basophil count (BASO#), are particularly important. These cells, generated by myeloid or lymphoid progenitors, are essential for immunity and are often used to diagnose or evaluate diseases such as appendicitis, acute pancreatitis, and more recently, COVID-19.
However, physiological development in children, especially during infancy and puberty, can cause significant changes in laboratory test results. For instance, serum alkaline phosphatase activity increases during puberty due to rapid bone growth and then declines as the child reaches adulthood. Similarly, total WBC and differential WBC counts also change with age. Therefore, interpreting these counts without considering age- and sex-dependent dynamics can lead to misdiagnosis or missed diagnosis.
This study aims to investigate age-dependent changes in total and differential WBC counts among healthy Chinese children aged 0 to 18 years. The data were obtained from the Pediatric Reference Intervals in China study (PRINCE), a nationwide multicenter cross-sectional study conducted from January 2017 to December 2018. The study used quantile curves calculated via the generalized additive models for location, shape, and scale (GAMLSS) method to analyze the 2.5th, 50th, and 97.5th quantiles of total and differential WBC counts. Additionally, percent stacked area charts were used to demonstrate the proportions of differential WBCs.
The results revealed that both the 50th and 97.5th quantiles of total WBC and monocyte counts were highest at birth and then rapidly decreased in the first six months of life. This was followed by a relatively slow reduction until two years of age. In contrast, lymphocyte counts were low during infancy, increased to their highest level at six months of age, and then exhibited moderate and continuous reduction until approximately nine years of age. Neutrophil counts showed an opposite pattern, with the highest levels at birth, rapid reduction until six months, and then mild and continuous elevation with age. Eosinophil and basophil counts did not exhibit significant age-related changes.
The study also found that the neutrophil-to-lymphocyte ratio (NLR) increased nearly three-fold from two to 18 years of age, with more rapid changes observed during puberty. Notably, sex differences were observed in NEUT#, LYMPH#, and EO# during puberty, likely due to the immunomodulatory effects of sex hormones. Estrogen, for example, can increase immunologic responses, while testosterone suppresses them.
The proportions of differential WBCs were also analyzed, revealing two intersections of lymphocyte and neutrophil counts during infancy and at approximately five years of age. These intersections indicate significant changes in the composition of WBCs during these periods.
The findings of this study have important clinical implications. Total and differential WBC counts are crucial for assessing immune status and diagnosing diseases in children. However, the reference intervals or clinical decision limits for these counts should be adjusted according to the age and sex of the child to avoid misdiagnosis or missed diagnosis. For example, the diagnostic performance of WBC counts in appendicitis varies significantly with age if the clinical decision limit is not adjusted.
Moreover, the study highlights the importance of understanding age-dependent changes in WBC counts for new infectious diseases, such as COVID-19. Many studies on COVID-19 have not investigated age-dependent changes in WBC counts, which could reduce their usefulness in treating children with the disease. The NLR and NEUT# have been identified as important clinical indicators for distinguishing COVID-19 from other viral infections in the early stages of the disease.
In conclusion, this study provides valuable data on age-dependent changes in total and differential WBC counts in healthy Chinese children. These data can aid in the application of WBC counts in clinical practice, ensuring proper clinical decisions and reducing the risk of misdiagnosis or missed diagnosis. The study also underscores the need for age- and sex-specific reference intervals for WBC counts to improve diagnostic efficiency and patient outcomes.
doi.org/10.1097/CM9.0000000000000854
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