Comprehensive pediatric reference intervals for 79 hematology markers in the CALIPER cohort of healthy children and adolescents using the Mindray BC-6800Plus system

Background

Hematological parameters vary significantly throughout growth and development due to physiological processes such as fetal-to-adult erythropoiesis and puberty. Pediatric age- and sex-specific reference intervals (RIs) are thus essential for appropriate clinical decision-making. The current study aimed to establish RIs for both common and novel hematology parameters on the Mindray BC-6800Plus system.

Methods

Six hundred and eighty-seven healthy children and adolescents (30 days to 18 years) were enrolled. Participants were recruited as part of the Canadian Laboratory Initiative on Pediatric Reference Intervals Program upon informed consent or identified from apparently healthy outpatient clinics. Whole blood was collected and assayed for 79 hematology parameters on the BC-6800Plus system (Mindray). Age- and sex-specific RIs were established as per Clinical and Laboratory Standards Institute EP28-A3c guidelines.

Results

Dynamic reference value distributions were observed for several hematology parameters, including erythrocytes, leukocytes, platelets, reticulocytes, and research-use-only markers. Age partitioning was required for 52 parameters, demonstrating changes in infancy and puberty. Sex partitioning was required for 11 erythrocyte parameters (i.e., red blood cell (RBC), hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin concentration, RBC distribution width coefficient of variation, hemoglobin distribution width, macrocyte count, macrocyte percentage, RBC (optical), and reticulocyte production index). Few parameters had undetectable levels in our healthy cohort (i.e., nucleated RBC count and immature granulocyte count).

Conclusions

The current study completed hematological profiling for 79 parameters on the BC-6800Plus system in a healthy cohort of Canadian children and adolescents. These data emphasize the complex biological patterns of hematology parameters in childhood, particularly at the onset of puberty, and support the need for age- and sex-specific RIs for clinical interpretation.     

Hematological indices reference intervals for a healthy Arab population in Qatar: Effect of age,gender, and geographic location

Hematologic reference intervals vary with gender, age, ethnicity, and geographic area. Therefore, local or national laboratory reference ranges are essential to enhance the accuracy when diagnosing health conditions. Still, no comprehensive list of reference ranges tailored to the Arab population living in Qatar. Accordingly, this study aims at establishing a hematology reference guide for Arabs in Qatar.This is a retrospective study where 750 healthy volunteers (18–69 years) from 2015 to 2019 were included, analyzed by an automated hematology analyzer. Arab adults were divided into African (Egypt, Libya, Tunisia, Morocco) and Asian (Syria, Lebanon, Jordon, Palestine, Qatar). The Cell-Dyn and Sysmex were used for measuring hematological parameters.The mean +/- 2SD were established for all the study groups. Arab males had significantly higher Hb, Hct, red cell distribution width, absolute neutrophil count, lymphocytes, and monocyte counts than females. Asian-Arab males had significantly higher Hb concentration and higher WBC, lymphocytes, and eosinophils than African Arabs. Asian-Arab young (>18: < 40 years) males had significantly higher Hb and lymphocytes and lower monocytes than older males (>40 years). African-Arab young males had significantly higher lymphocytes and lower monocytes than older males. Asian-Arab young females had higher WBC and absolute neutrophil count than older Asian Arabs.The findings of this study will help in establishing specific reference intervals in the Arab world. The differences in hematology reference intervals considering age, gender, and geographical location highlight the importance of establishing blood reference intervals in each country considering the ethnic diversity of each country.     

Effects of circadian variation,lifestyle and environment on hematological parameters: A narrative review

The complete blood count (CBC) is the most widely prescribed laboratory test. It plays a key role in screening, diagnosing, and monitoring a variety of medical disorders. Preanalytical and analytical variables are responsible for more than 50% of laboratory errors that may lead to spurious CBC results. The effects of blood sampling, transport, storage, and analytical errors on hematological parameters have been well described. Circadian variation and changes in lifestyle and environment can also affect blood cells. It has been extensively studied in the past, but highly variable methodology and the presence of confounding factors have provided scattered and inconsistent results. We have investigated the literature to define the impact of circadian variation, modification of the sleep-wake cycle, acute and chronic exercise, eating habits, alcohol, tobacco, drugs of abuse, high-altitude, heat/cold exposure, and air pollution on CBC results. The affected cell type along with the intensity and duration of changes are detailed for each condition. We aim at providing a comprehensive overview of which situations may induce clinically significant changes and have to be taken into account by healthcare professionals before considering a hematological parameter as pathological and requesting complementary tests.     

Haematological and biochemical indices in young African children: in search of reference intervals

INTRODUCTION: The reference intervals of haematological and biochemical indices currently used in Africa are derived from data collected from populations living in industrialized countries. Few studies have been performed in Africa questioning the validity of these values when applied to local African populations. OBJECTIVE: To provide reference intervals of haematological [haemoglobin (Hb), white blood cells (WBC), haematocrit (Htc) and platelets] and biochemical indices (ALT, creatinine and bilirubin) for children aged 1-4 from a rural area of southern Mozambique. METHODS: Reference intervals were developed using the 2.5 and 97.5 centiles. Partition tests were performed to evaluate age and gender differences. Quantile regression models were estimated for those variables in which age partition was recommended. Deviances from linearity in the estimated models were evaluated using fractional polynomials of first or second degree. Agreement to classify normality, using the estimated reference intervals or values in use in a western paediatric hospital, was made using the kappa statistic. RESULTS: Reference intervals for Hb, WBC, Htc, platelets, ALT and creatinine show significant differences by age. Gender differences were observed for creatinine values, while for bilirubin there were no significant differences for age or gender. Estimated Hb and Htc reference intervals in African children were lower than the accepted western ones, while ALT values were higher in the former. Agreement between normal classification, using the estimated intervals or the western values, was from slight to fair. CONCLUSIONS: Reference intervals of haematological and biochemical indices based on results from western individuals of the same age are not in agreement with the estimated values for African children. These observed values should not be used as a rule to define normality, but are the ones usually found in this population where anaemia, malaria and high mortality rates are also common.     

Normative reference values for lung transfer factor in Isfahan, Iran

OBJECTIVES AND BACKGROUND: Transfer factor or carbon monoxide diffusing capacity (DL(CO)) is a particularly valuable test of the appropriateness of gas exchange across the alveolocapillary membrane. The purpose of this study is to derive predictive equations for DL(CO) and its derivative volume-corrected DL(CO) (DL(CO)/VA) measured by single-breath method in a large non-smoking population sample in Isfahan. METHODOLOGY: We evaluated 1429 randomly selected subjects (732 men, aged 5-85 years). Gender-specific linear prediction equations were developed by multiple regression analysis; with measured DL(CO), and DL(CO)/VA values (mmol/min/kPa), as dependent variables regressed against age (A), height (H) and body surface area (BSA). RESULTS: For both genders, age had negative effects on DL(CO), while height had a positive effect on DL(CO) and DL(CO)/VA (P < 0.01). The prediction equations for DL(CO) and DL(CO)/VA are: '0.152 x height - 0.056 x age - 11.595' and '-0.12 x age + 2.467', for men and: '-0.035 x age - 0.133 x height - 10.707' and '-0.012 x age - 0.02 x height + 2.755', for women, respectively. CONCLUSIONS: Our results therefore provide an original frame of reference for either DL(CO) or DL(CO)/VA in Iranian population, obtained from a standardized single-breath technique.     

Blood haemoglobin declines in the elderly: implications for reference intervals from age 70 to 88

The objective was to determine whether Hb declines in healthy elderly men and women and if this influences health-related reference intervals. A representative population sample, comprising 30% of all 70-yr-old subjects in a Swedish city with 420,000 inhabitants (n = 1148, participation rate 85%), was followed at 1-5-yr intervals for 18 yr within a longitudinal population study. Age-related changes in Hb were calculated after exclusion of non-healthy probands and by multivariate analyses in the total study group. Mean Hb declined between age 70 and 88 from 149 to 138 g/L in men (annual decline 0.69 g/L, p = 0.000), and from 139 to 135 g/L in women (annual decline 0.06 g/L, n.s.). Healthy men declined from 152 to 141 g/L (annual decline 0.53 g/L, p = 0.038), for women from 140 to 138 g/L (annual decline 0.05 g/L, n.s.). Age and body mass index correlated, in multivariate analysis, independently to Hb in both men and women, as did variables indicating a non-healthy state. Epidemiological decision limits for anaemia declined for men from 128 to 116 g/L, for women from 118 to 114 g/L. Anaemia, thus defined, occurred in 3.2 to 9.7% of the subjects, whereas 28.3% of the 88-yr-old men had anaemia according to the WHO definition. In conclusion, there is a significant age-related decline in Hb from age 70 to 88 among healthy men, and a less pronounced decline among women. This justifies the use of lower epidemiological decision limits for anaemia of about 115 g/L for both men and women from age 80-82.     

Are different reference intervals for methylmalonic acid and total homocysteine necessary in elderly people?

Abstract: To determine whether age-adjusted reference intervals for methymalonic acid (MMA) and total homocysteine (tHcy) are necessary, data from 2 previous studies were used. First, the reference intervals for serum vitamin B₁₂, folate, methylmalonic acid and total homocysteine were determined in 2 reference sample groups: 99 healthy adults and 64 selected healthy elderly subjects living at home. Secondly, health-related reference limits were estimated in 143 elderly subjects after supplementing the nutritional status with a combination of vitamin B₁₂, vitamin B₆ and folate during a 3-wk period. In the latter group, the adjusted reference intervals for MMA (46–288 nmol/L) as well as for tHey (5–13.6 μmol/L) are different with considerably lower upper reference limits than that estimated with the original reference values (72–476 nmol/L for MMA; 6.8–21 μmol/L for tHcy) in the elderly subjects. Our data suggest that the MMA and tHcy levels increase with age. Moreover, the upper reference limit for MMA and tHcy, conventionally defined as the mean +2 SD in a healthy elderly reference sample group without supplementing the nutritional status, might result in falsely high values due to a high prevalence of an inadequate vitamin B₁₂, vitamin B₆ and folate status.     

长春地区成人血清甲胎蛋白、癌胚抗原参考区间适用性验证

目的 验证卫生行业标准WS/T 645.2-2018中血清甲胎蛋白、癌胚抗原参考区间是否适用于长春地区。方法 按照WS/T 645.2-2018参考区间验证方法,入组2016年1月-2019年4月在吉林大学第一医院体检中心体检的20~79岁健康体检者5420例,根据年龄和性别划分为12个亚组,验证各组落入参考区间的检测值是否>90%,分析血清甲胎蛋白、癌胚抗原随年龄及性别变化趋势。计量资料两组比较采用Mann-Whitney U检验。结果 血清甲胎蛋白和癌胚抗原各亚组测量值90%以上落在参考区间内,通过参考区间验证。血清甲胎蛋白在30~39岁存在性别差异(Z=-4.51, P<0.05),血清癌胚抗原在20~29岁、30~39岁、40~49岁、50~59岁、60~69岁均存在性别差异(Z值分别为-13.45、-18.15、-17.34、-10.82、-3.65,P值均<0.05);血清甲胎蛋白在女性20~69岁随年龄缓慢上升,70~79岁男性及女性均随年龄下降;血清癌胚抗原在女性20~79岁、男性20~79岁随年龄上升,且男性检测值高于女性。结论 国家卫生健康委员会发布的WS/T 645.2-2018中血清甲胎蛋白、癌胚抗原参考区间适用于长春地区。     

The association between hematological parameters and metabolic syndrome in Iranian men: A single center large-scale study

Aims

Some studies have demonstrated that metabolic syndrome is associated with hematological parameters. The present study explores the relationship between hematological parameters and numbers of metabolic syndrome conditions in Iranian men.

Reference intervals and percentiles for carotid‐femoral pulse wave velocity in a healthy population aged between 9 and 87 years

There is little information regarding age‐related reference intervals (RIs) of carotid‐femoral pulse wave velocity (cfPWV) for large healthy populations in South America. The aims of this study were to determine cfPWV RIs and percentiles in a cohort of healthy children, adolescents, and adults and to generate year‐to‐year percentile curves and body‐height percentile curves for children and adolescents. cfPWV was measured in 1722 healthy participants with no cardiovascular risk factors (9–87 years, 60% men). First, RIs were evaluated for males and females through correlation and covariate analysis. Then, mean and standard deviation age‐related equations were obtained for cfPWV using parametric regression methods based on fractional polynomials and age‐specific (year‐to‐year) percentile curves that were defined using the standard normal distribution. Age‐specific first, 2.5th, 5th, 10th, 25th, 50th, 75th, 90th, 95th, 97.5th, and 99th percentile curves were calculated. Finally, height‐related cfPWV percentile curves for children and adolescents (<21 years) were established. After adjusting for age and blood pressure differences with respect to females, males showed higher cfPWV levels (6.60 vs 6.45 m/s; P < .01). Thus, specific RIs for males and females were reported. The study provides the largest database to date concerning cfPWV in healthy people from Argentina. Specific RIs and percentiles of cfPWV are now available according to age and sex. Specific percentiles of cfPWV according to body height were reported for people younger than 21 years.     

Static lung volumes and airway resistance reference values in healthy adults

Background and objective: The assessment of static lung volumes and airway resistance is a frequently performed diagnostic procedure and considered as an important tool in medical surveillance to detect pulmonary diseases. The objectives of the study are to establish reference equations for body plethysmographic parameters in a representative adult population across a wide age range and to compare the normative values from this sample with previous ones. Methods: Body plethysmography was applied in 1809 participants (885 males) of a cross‐sectional, population‐based survey (Study of Health in Pomerania). Individuals with cardiopulmonary disorders and/or a pack‐year smoking history >10 years and participants with a body mass index >30 kg/m² were excluded. In total, 686 healthy individuals (275 males) aged 25–85 years were assessed. Results: Prediction equations for both genders were established by quantile regression analysis taking into account the influence of age, height and weight. Conclusions: The study provides a novel set of prediction equations for static lung volumes and airway resistance obtained using body plethysmography. Compared with our findings, existing equations underestimated some normal values. The results emphasize the need for up‐to‐date reference equations.     

Reference intervals of aortic pulse wave velocity assessed with an oscillometric device in healthy children and adolescents from Argentina

Age-related reference intervals (RIs) of aortic pulse wave velocity (Ao-PWV) obtained from a large healthy population are lacking in South America. The aims of this study were to determine Ao-PWV RIs in a cohort of healthy children and adolescents from Argentina and to generate year-to-year percentile curves.

Ao-PWV was measured in 1000 healthy subjects non-exposed to traditional cardiovascular risk factors (Age: 10–22 y. o., 56% males). First, we evaluated if RIs for males and females were necessaries (correlation and covariate analysis). Second, mean (M) and standard deviation (SD) age-related equations were obtained for cf-PWV, using parametric regression methods based on fractional polynomials. Third, age-specific (year to year) percentiles curves (for all, males and females children and adolescents) were generated using the standard normal distribution. They were, age-specific 1st, 2.5th, 5th, 10th, 25th, 50th, 75th, 90th, 95th, 97.5th and 99th percentile curves and values.

After covariate analysis (i.e., adjusting by age, jugulum-symphysis distance, body weight and height), specific RIs for males and females of children and adolescents were evidenced as necessaries. The equations were

For all subjects:

Ao-PWV_Mean = 4.98 + 12.86x10^?5 Age³.

Ao-PWV_SD = 0.47 + 21.00x10^?6Age³.

For girls:

Ao-PWV_Mean = 5.07 + 10.23x10^?5Age³.

Ao-PWV_SD = 0.50 + 10.00x10^?6Age³.

For boys:

Ao-PWV_Mean = 4.87 + 15.81x10^?5Age³.

Ao-PWV_SD = 0.46 + 22.34x10^?6Age³.

Our study provides the largest database to-date concerning Ao-PWV in healthy children and adolescents in Argentina. Age-related equations (M and SD values) for Ao-PWV are reported by the first time. Specific RIs and percentiles of Ao-PWV are now available according to age and sex for an Argentinian population.