Age-Dependent Changes in Total and Differential White Blood Cell Counts in Children

0
0
0

Age-Dependent Changes in Total and Differential White Blood Cell Counts in Children

Introduction

The complete blood count (CBC) is a crucial laboratory test in clinical practice. It is used not only for diagnosing sick patients but also in wellness screening programs. White blood cell (WBC) count and differential WBCs, such as monocyte count (MONO#), lymphocyte count (LYMPH#), neutrophil count (NEUT#), eosinophil count (EO#), and basophil count (BASO#), are vital for disease diagnosis or evaluation as these cells play essential roles in immunity. For example, total WBC and differential WBC percentages are included in the diagnostic evaluation of suspected appendicitis or acute pancreatitis. Additionally, recent findings suggest that lymphocyte changes in COVID-19 patients should be carefully monitored.

However, physiological development can cause changes in laboratory test results, especially during infancy and puberty. Just like serum alkaline phosphatase activity changes with a child’s growth, the total WBC and differential WBCs also change with age. Without considering age – and sex – dependent dynamics, unadjusted diagnostic evaluation based on laboratory tests may lead to misdiagnosis or missed diagnosis.

In China, age – dependent changes in WBCs in children have rarely been reported. This study, based on the Pediatric Reference Intervals in China study (PRINCE), aims to investigate these changes in healthy children aged 0 to 18 years.

Methods

Ethical Approval

The study was conducted in accordance with the Declaration of Helsinki. The PRINCE study protocol was approved by the Institutional Review Board of Beijing Children’s Hospital, and the current study protocol using PRINCE data was approved by the institutional review boards of ten collaborating centers. Informed consent was obtained from the legally authorized representatives of children under 8 years old, and assent was obtained from children aged 8 years and above along with consent from their representatives.

Data Source

Data were from the PRINCE study. 15,150 healthy children aged 0 to 19 years were recruited from various regions of China from January 2017 to December 2018. Participants aged 0 to 18 years were included in this exploration.

Laboratory Examinations

Blood specimens were collected by trained pediatric nurses using BD vacutainer and vacuum tube needles. The CBC was performed using an automated hematology analyzer, Sysmex XS.

Data Cleaning and Management

Data cleaning was done to detect missing values and outliers. Missing values were those without information on age, sex, or CBC results. Test results affected by specimen quality (like hemolysis) were excluded. Outliers were tested using the Tukey method. When variables didn’t have a Gaussian distribution, the Box – Cox method was used for transformation.

Statistical Analysis

All statistical analyses were performed using R software. Percentiles were estimated using the generalized additive models for location, shape, and scale (GAMLSS) method. Separate charts were constructed for the first 2 years of life to show dynamic changes. Percent of stacked area charts were used to show differential WBC proportions.

Results

Data Cleaning

Some results of MONO# and EO# reported as zero were excluded. The medians and inter – quartile ranges of total and differential WBCs are shown in Table 1. The total WBC decreased with age. Similar changes were seen in MONO#, EO#, and BASO#. LYMPH# was highest in the 6 – month – to – less – than – 2 – year age group and then decreased. NEUT# changes were opposite to LYMPH#.

Age – Dependent Changes

  • WBC and MONO#: The 50th and 97.5th quantiles were highest at birth, then rapidly decreased in the first 6 months, with a relatively slow reduction until 2 years. Males had a slightly higher MONO#, and females had a slightly higher WBC during puberty.
  • LYMPH#: Low during infancy, increased to the highest level at 6 months, then moderately and continuously reduced until about 9 years. Males had slightly higher LYMPH# during puberty.
  • NEUT#: Highest at birth, rapidly reduced until 6 months. While WBC and MONO# continued to reduce, NEUT# showed mild and continuous elevation. The neutrophil – to – lymphocyte ratio (NLR) showed more rapid age – dependent changes during puberty, increasing nearly three – fold from 2 to 18 years. Females had higher NLR and NEUT# during puberty.
  • EO# and BASO#: No apparent age – related changes in the 2.5th and 50th quantiles. The 97th quantiles showed mild reduction throughout childhood.

Proportions of Differential WBCs

Percent stacked area charts showed the proportions. There were two intersections of LYMPH# and NEUT# during infancy and at about 5 years.

Discussion

Total and differential WBCs are important for assessing children’s immune status and diagnosing diseases. For example, in pneumonia, the NLR, WBC, and NEUT# are important for differentiating viral and bacterial pneumonia. Early exclusion of bacterial pneumonia can reduce unnecessary antibiotic use. In COVID – 19, lymphocyte changes and the NLR may be important clinical indicators.

This study showed dramatic changes in total and differential WBCs in childhood. LYMPH# and NEUT# had more obvious age – dependent changes. These findings support the need to modify reference intervals or clinical decision limits according to children’s growth. For example, in appendicitis diagnosis, not adjusting for age can affect diagnostic performance.

Mild sex differences in NEUT#, LYMPH#, and EO# were seen during puberty, likely due to sex hormones acting as immunomodulators. Although BASO# had fewer age – dependent changes, its changes during bacterial infection can affect patient outcomes.

Total and differential WBCs have potential uses beyond routine diagnosis. Neutrophils may have roles in cancer – related inflammation and prognosis assessment. The NLR can predict the severity of some diseases like hypertriglyceridemia – induced acute pancreatitis and aid in the diagnosis of others like ankylosing spondylitis.

This study has limitations. The GAMLSS – calculated quantile curves had an edge – effect, possibly due to a relatively small sample size, especially for young children. Recruiting healthy infant volunteers and collecting blood from infants are difficult.

Conclusion

Understanding age – dependent changes in total and differential WBCs is crucial for pediatric clinical decisions. Our data on these changes can help assess children’s health and guide clinical practice.

[1] Shapiro MF, Greenfield S. The complete blood count and leukocyte differential count. An approach to their rational application. Ann Intern Med 1987;106:65–74. doi: 10.7326/0003 – 4819 – 106 – 1 – 65. [2] Huang L, Chen C, Yang L, Wan R, Hu G. Neutrophil – to – lymphocyte ratio can specifically predict the severity of hypertriglyceridemia – induced acute pancreatitis compared with white blood cell. J Clin Lab Anal 2019;33:e22839. doi: 10.1002/jcla.22839. [3] Lavoignet CE, Le Borgne P, Chabrier S, Bidoire J, Slimani H, Chevrolet – Lavoignet J, et al. White blood cell count and eosinopenia as valuable tools for the diagnosis of bacterial infections in the ED. Eur J Clin Microbiol Infect Dis 2019;38:1523–1532. doi: 10.1007/s10096 – 019 – 03583 – 2. [4] Liu J, Liu Y, Xiang P, Pu L, Xiong H, Li C, et al. Neutrophil – to – lymphocyte ratio predicts severe illness patients with 2019 novel coronavirus in the early stage. medRxiv 2020. doi: 10.1101/2020.02.10.20021584 [5] Zierk J, Arzideh F, Haeckel R, Cario H, Fruhwald MC, Gross HJ, et al. Pediatric reference intervals for alkaline phosphatase. Clin Chem Lab Med 2017;55:102–110. doi: 10.1515/cclm – 2016 – 0318. [6] Loh TP, Metz MP. Trends and physiology of common serum biochemistries in children aged 0 – 18 years. Pathology 2015;47:452–461. doi: 10.1097/pat.0000000000000274. [7] Zierk J, Arzideh F, Rechenauer T, Haeckel R, Rascher W, Metzler M, et al. Age – and sex – specific dynamics in 22 hematologic and biochemical analytes from birth to adolescence. Clin Chem 2015;61:964–973. doi: 10.1373/clinchem.2015.239731. [8] Ni X, Song W, Peng X, Shen Y, Peng Y, Li Q, et al. Pediatric reference intervals in China (PRINCE): design and rationale for a large, multicenter collaborative cross – sectional study. Sci Bull 2018;63:1626–1634. doi: 10.1016/j.scib.2018.11.024. [9] Peng X, Lv Y, Feng G, Peng Y, Li Q, Song W, et al. Algorithm on age partitioning for estimation of reference intervals using clinical laboratory database exemplified with plasma creatinine. Clin Chem Lab Med 2018;56:1514–1523. doi: 10.1515/cclm – 2017 – 1095. [10] Stasinopoulos DM, Rigby RA. Generalized additive models for location scale and shape (GAMLSS) in R. J Stat Softw 2007;23. doi: 10.18637/jss.v023.i07. [11] Voncken L, Albers CJ, Timmerman ME. Model selection in continuous test norming with GAMLSS. Assessment 2019;26:1329–1346. doi: 10.1177/1073191117715113. [12] Li J, Zhang H, Huang X, Zhang J, Wu X. Establishment of reference intervals for complete blood count parameters in venous blood for children in the Xiamen area, China. Int J Lab Hematol 2019;41:691–696. doi: 10.1111/ijlh.13095. [13] Ruuskanen O, Lahti E, Jennings LC, Murdoch DR. Viral pneumonia. Lancet (London, England) 2011;377:1264–1275. doi: 10.1016/s0140 – 6736(10)61459 – 6. [14] Virkki R, Juven T, Rikalainen H, Svedstrom E, Mertsola J, Ruuskanen O. Differentiation of bacterial and viral pneumonia in children. Thorax 2002;57:438–441. doi: 10.1136/thorax.57.5.438. [15] Bhuiyan MU, Blyth CC, West R, Lang J, Rahman T, Granland C, et al. Combination of clinical symptoms and blood biomarkers can improve discrimination between bacterial or viral community – acquired pneumonia in children. BMC Pulm Med 2019;19:71. doi: 10.1186/s12890 – 019 – 0835 – 5. [16] You Q, Huang ZM, Guo H, Chen J, Li J. Value of inflammatory indexes and blood routine in differential diagnosis of viral and bacterial pneumonia patients and in prediction of complications [in Chinese]. Chin J Nosocomial 2018;28:1342–1344. doi:10.11816/cn.ni.2018 – 172791. [17] National Health Commission of the People’s Republic of China. Guidelines for the Diagnosis and Treatment of Novel Coronavirus (2019 – nCoV) Infection by the National Health Commission (Trial Version 6) 2020. Available from: http://www.nhc.gov.cn/yzygj/s7653p/202002/8334a8326dd94d329df351d7da8aefc2/files/b218cfeb1bc54639af227f922bf6b817.pdf. [Accessed February 18, 2020] [18] Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet (London, England) 2020;395:507–513. doi: 10.1016/s0140 – 6736(20)30211 – 7. [19] Brandau S, Dumitru CA, Lang S. Protumor and antitumor functions of neutrophil granulocytes. Semin Immunopathol 2013;35:163–176. doi: 10.1007/s00281 – 012 – 0344 – 6. [20] Bachur RG, Dayan PS, Dudley NC, Bajaj L, Stevenson MD, Macias CG, et al. The influence of age on the diagnostic performance of white blood cell count and absolute neutrophil count in suspected pediatric appendicitis. Acad Emerg Med 2016;23:1235–1242. doi: 10.1111/acem.13018. [21] Jiang JY, Duan L, Xiong DX, Feng Y, Liu XJ, Yu J, et al. Epidemiological and clinical characteristics of novel coronavirus infection in children: thoughts on the diagnostic criteria of suspected cases outside Hubei Province [in Chinese]. Chin Pediatr Emerg Med 2020;27:E003–E003. doi: 10.3760/cma.j.issn.1673 – 4912.2020.0003. [22] Verthelyi D. Sex hormones as immunomodulators in health and disease. Int Immunopharmacol 2001;1:983–993. doi: 10.1016/S1567 – 5769(01)00044 – 3. [23] Donskov F, von der Maase H. Impact of immune parameters on long – term survival in metastatic renal cell carcinoma. J Clin Oncol 2006;24:1997–2005. doi: 10.1200/jco.2005.03.9594. [24] Dumitru CA, Moses K, Trellakis S, Lang S, Brandau S. Neutrophils and granulocytic myeloid – derived suppressor cells: immunophenotyping, cell biology and clinical relevance in human oncology. Cancer Immunol Immunother 2012;61:1155–1167. doi: 10.1007/s00262 – 012 – 1294 – 5.

doi:10.1097/CM9.0000000000000854

Was this helpful?

0 / 0