Reference intervals for serum cystatin C in Brazilian children aged 5-11 years: A short report.

Continuous reference intervals for 38 biochemical markers in healthy children and adolescents: Comparisons to traditionally partitioned reference intervals

Objective To establish the biological reference intervals of serum immunoglobulin (Ig) for children (neonates to young adults) in our laboratory. Methods This was a retrospective study. Serum IgG, IgA and IgM of the neonatal (1–28 days) to 18 years old who visited the First Hospital of Jilin University during January 2011 to July 2014 were measured. The inclusion criteria were normal C–reactive protein content, normal liver and kidney function and without history of chronic diseases, allergic reactions, connective tissue diseases, rheumatic diseases and human immunodeficiency diseases. Children whose Ig tests were below upper limit of adult reference range were divided into 19 age groups. By eliminating outliers within each group, 9 466 cases of reference individuals conformed to the establishment of reference intervals were selected. Rank sum test was applied in comparing Ig levels of each two adjacent age groups, if there was not statistical significance (P>0.05), the two age groups were merged; otherwise not merged. The upper and lower limit of Ig reference range for each age group were calculated using nonparametric method, and biological reference intervals of children's serum Ig were established. Results The neonatal serum IgG decreased grually after birth and reached the lowest point at 29 days–3 months, then the concentration increased gradually along with age growth and reached adult level by 11 years old. Neonatal serum IgA and IgM levels were at the lowest point and the concentration increased along with age growth then reached adult levels by 11 and 2 years old respectively. The children's serum Ig reference intervals were as below: IgG: 3.59–7.90, 2.26–5.40, 2.72–6.62, 2.87–7.74, 3.38–8.07, 3.80–9.08, 4.86–11.40, 4.97–11.70, 5.51–12.40, 6.17–13.10, 6.41–13.60, 6.53–14.20 and 6.84–14.30 g/L for neonatal, 29 days–3 months, 4–6 months, 7 months, 8–9 months, 10 months–1 year old, 2, 3, 4, 5–6, 7, 8 and 9–10 years old, respectively; IgA: 0.23–0.45, 0.24–1.02, 0.23–0.79, 0.23–0.92, 0.24–1.03, 0.24–1.56, 0.26–1.93, 0.31–2.16, 0.44–2.56, 0.56–2.85, 0.52–3.35 and 0.63–3.23 g/L for neonatal–3 months, 4 months, 5–7 months, 8–9 months, 10 months –1 years old, 2, 3, 4, 5–6, 7, 8, and 9–10 years old, respectively; IgM: 0.16–0.70, 0.21–1.20, 0.30–1.62, 0.38–2.16 and 0.44–2.17 g/L for neonatal, 29 days–3 months, 4–7 months, 8–9 months and 10 months–1 years old, respectively. Conclusions There were great differences of the serum Ig concentrations between children and adults, thus children's immunologic function should not be assessed based on adult Ig reference intervals. According to the research, reference intervals of Ig were obtained for children at different age groups in the laboratory and reference in evaluating children's immunologic function was provided for clinicians. (Chin J Lab Med, 2015, 38: 191–195) Key words: Immunoglobulin; Child; Reference value

The use of kidney function and injury markers for early detection of drug-related glomerular or tubular kidney injury in infants, children and adolescents requires age-specific data on reference intervals in a pediatric healthy population. This study characterizes serum values for eight kidney function and injury markers in healthy infants, children and adolescents. A single center prospective observational study was conducted between December 2018 and June 2019. Serum samples from 142 healthy infants, children and adolescents aged between 0 and≤15 years were collected. Statistical analyses for eight markers (albumin (ALB), β2-microglobulin (B2M), β-trace protein (BTP), creatinine (SCR), cystatin C (CYSC), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), uromodulin (URO)) were performed to obtain reference intervals and associations with age, sex and weight were investigated (Pearson correlation, linear and piecewise regression). ALB and SCR increased with age (p<0.01), whereas B2M, BTP and KIM-1 values decreased with advancing age (p<0.05) in this healthy pediatric study population. CYSC showed dependency on sex (lower concentration in females) and decreased with age until reaching approximately 1.8 years; thereafter an increase with age was seen. NGAL and URO did not show any age-dependency. This study provides age appropriate reference intervals for key serum kidney function and injury markers determined in healthy infants, children and adolescents. Such reference intervals facilitate the interpretation of changes in kidney function and injury markers in daily practice, and allow early detection of glomerular and tubular injury in infancy, childhood and adolescence.

To date, China has no industry standard for reference intervals of paediatric blood biochemical markers. This study aimed to evaluate changes in biochemical markers in the venous blood of healthy children aged 29 days to 12 years, derived from the UniCel DxC 800 system, and establish appropriate reference intervals. We analysed venous blood from 1980 healthy children for 20 biochemical markers. Reference intervals were established according to the Clinical and Laboratory Standards Institute C28-A3c guideline and compared with those of adults in China. All markers except for sodium and chlorine required partitioning by age, but not by sex. The reference intervals of total protein, albumin, globulin, carbon dioxide, urea nitrogen, creatinine and uric acid consistently increased with age in children, but were always lower than those of adults. Children aged 29 days to 12 years had a single combined RI for sodium and chloride, respectively; although the reference intervals in children were similar to those of adults, their upper limits were lower. The reference intervals of direct bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, potassium, calcium, magnesium, and phosphorus continued to decline with age. The reference intervals of total bilirubin, indirect bilirubin, and gamma-glutamyl transpeptidase initially declined followed by a slight rebound. While establishing reference intervals, most markers required partitioning by age (aged 29 days to 12 years); the partitioning scheme differed for each marker, and paediatric reference intervals differed from those for adults. It is therefore necessary to establish separate paediatric reference intervals.

Background Laboratory measurements of trace elements such as magnesium (Mg), copper (Cu) and zinc (Zn) in red blood cells (RBCs) are used to assess nutritional status and diagnose metal toxicity. The purpose of this study was to develop/validate an ICP-MS method for the quantification of these elements in RBCs. Methods An aliquot of packed RBCs was diluted in alkaline diluent solution containing scandium (45Sc) and gallium (71Ga), as internal standards, 0.1% Triton X-100, 0.1% EDTA, and 1% ammonium hydroxide (NH4OH). The diluted specimen was aspirated onto an ICP-MS for quantitative analysis of 25Mg, 63Cu and 66Zn. The method was validated for accuracy, precision, method comparison, linearity, analytical sensitivity, and carryover. Retrospective data was analyzed and non-parametric reference intervals (RIs) were calculated. Results Accuracy and linearity were within the expected range of =±15% for all analytes. Within-run, between-run, and total imprecisions were =15% CV. All other validation experiments met acceptance criteria. Established RIs for Mg, Cu and Zn in RBCs are 3.6-7.5 mg/dL, 59.0-91.0 mcg/dL and 794.0-1470.0 mcg/dL, respectively. Retrospective analysis of patient data for Mg RBC displayed no statistically significant difference in mean concentrations between adults (&amp;gt;18+ yr) and children (0-18 yr) (p &amp;gt;0.05); however, there was a significant difference in Mg concentrations between males and females (p &amp;lt; 0.001). The mean and SD for Mg RBC concentration for females and males were 5.38 + 0.68 mg/dL (n=8451) and 5.42 + 0.68 mg/dL (n=3954) respectively. The 95% RI was 4.2-6.9 mg/dL; &amp;gt;99% of patient results were within the established RI. Cu RBC mean concentrations were not statistically significant between males and females (p&amp;gt; 0.05) and age differences were not evaluated due to the low number of pediatric patients (n=37). The mean and SD for Cu concentrations were 72.2 + 11.7 mcg/dL (n=423). The overall 95% RI was 54.3-96.3 mcg/dL; 88.9% of patient results were within the established RI. For Zn RBC, there was a statistically significant difference in mean concentrations between children and adults (p &amp;lt; 0.0001) and no statistically significant difference between sex (p &amp;gt; 0.05). The mean and SD for Zn concentrations in children were 1103.7 + 225.5 mcg/dL (n=188). The 95% RI for this subgroup was 707.3– 1547.6 mcg/dL; 87.8% of pediatric patients were within the established RI. In adults, the mean and SD for Zn concentrations were 1311.7 + 196.2 mcg/dL (n=1579). The 95% RI was 932.5 – 1718.3 mcg/dL; 83.3% of patient results were within the established RI. Conclusions This method was validated and met criteria for clinical use to quantify three elements using ICP-MS for biological monitoring. Retrospective data analysis of patient results demonstrated that the method was suitable to assess nutritional deficiency and toxicity.

Prevalence of elevated blood pressure in pediatric population has been increasing worldwide. Thus, the aim of this study was to examine whether the triglycerides and glucose (TyG) index is associated with the presence of prehypertension or hypertension in children and adolescents. Apparently healthy children aged 6 to 15years were enrolled in a population-based cross-sectional study. Participants were allocated into groups with normal blood pressure (NBP), prehypertension, and hypertension. Smoking, alcohol intake, pregnancy, previous diagnosis of diabetes, kidney, hepatic, or endocrine diseases were exclusion criteria. NBP was defined by systolic and/or diastolic blood pressure < 90th percentile, prehypertension by systolic and/or diastolic blood pressure ≥ 90th < 95th percentile, and hypertension by systolic and/or diastolic blood pressure ≥ 95th percentile, according to age, sex, and height percentiles. A total of 3589 children were enrolled, 1748 (49%) girls and 1841 (51%) boys, and allocated into groups with NBP (n = 2874), prehypertension (n = 271), and hypertension (n = 444). The multiple logistic regression analysis stratified by age and adjusted by the Z-score/SDS of body mass index and waist circumference showed that elevated TyG index was significantly associated with prehypertension (OR = 1.48; 95% CI: 1.08-2.05) and hypertension (OR = 1.63; 95% CI: 1.26-2.11).Conclusion: The results of the present study shows that the elevated TyG index is significantly associated with the presence of prehypertension and hypertension in children and adolescents. What is Known: • Prevalence of elevated blood pressure in children and adolescents has been increasing worldwide. • Insulin resistance plays a key role in the pathogenesis of hypertension. What is New: • The elevated TyG index is significantly associated with the presence of prehypertension in children aged 6-9years and adolescents aged 10-15years. • The elevated TyG index is significantly associated with the presence of hypertension in children aged 6-9years and adolescents aged 10-15years.

Evidence suggests that decreased α-tocopherol (the most biologically active substance in the vitamin E group) level can cause neurological symptoms, most likely ataxia. The aim of the current study was to first provide reference intervals for serum tocopherols in the adult Hungarian population with appropriate sample size, recruiting healthy control subjects and neurological patients suffering from conditions without symptoms of ataxia, myopathy or cognitive deficiency. A validated HPLC method applying a diode array detector and rac-tocol as internal standard was utilized for that purpose. Furthermore, serum cholesterol levels were determined as well for data normalization. The calculated 2.5-97.5% reference intervals for α-, β/γ- and δ-tocopherols were 24.62-54.67, 0.81-3.69 and 0.29-1.07 μm, respectively, whereas the tocopherol/cholesterol ratios were 5.11-11.27, 0.14-0.72 and 0.06-0.22 μmol/mmol, respectively. The establishment of these reference intervals may improve the diagnostic accuracy of tocopherol measurements in certain neurological conditions with decreased tocopherol levels. Moreover, the current study draws special attention to the possible pitfalls in the complex process of the determination of reference intervals as well, including the selection of study population, the application of internal standard and method validation and the calculation of tocopherol/cholesterol ratios.

Biochemical substances relating to renal and hepatic function are influenced not only by individual factors such as gender, lifestyle, and age but also by ecological factors, such as altitude, climate, and ethnic background. The purpose of the present study was to establish reference intervals for 16 biochemical substances relating to renal and hepatic function in healthy Chinese adults. A total of 2,405 apparently healthy individuals (18-77 years of age) were chosen as reference individuals in the present study. The 16 biochemical substances relating to renal and hepatic function were analyzed using a HITACHI RL7600 analyzer. The reference intervals were established using nonparametric methods to estimate the 2.5 and 97.5 percentiles of the distribution as the lower and the upper limits, respectively. Age- and gender-appropriate reference intervals were established for some biochemical substances relating to renal and hepatic function in healthy Chinese adults. The reference intervals established in this study can provide a useful clinical tool for the assessment of the kidney and liver damage. In addition, the established reference intervals can be adopted in other clinical laboratories after further validation.

To determine the normal haematological and immunological reference intervals for healthy Tanzanian children. We analysed data from 655 HIV-seronegative, healthy children from 1 month to 18 years of age from the Kilimanjaro Region of Tanzania for this cross-sectional study. Median and 95% reference ranges were determined for haematological and immunological parameters and analysed by age cohorts, and by gender for adolescents. Median haemoglobin (Hb) and haematocrit (Hct) for all age groups were higher than established East African reference intervals. Compared to U.S. intervals, reference ranges encompassed lower values for Hb, Hct, mean corpuscular volume, and platelets. Applying the U.S. National Institute of Health Division of AIDS (DAIDS) adverse event grading criteria commonly used in clinical trials to the reference range participants, 128 (21%) of 619 children would be classified as having an adverse event related to Hb level. CD4-positive T-lymphocyte absolute counts declined significantly with increasing age (P < 0.0001). For those aged under five years, CD4-positive T-lymphocyte percentages are lower than established developed country medians. Country-specific reference ranges are needed for defining normal laboratory parameters among children in Africa. Knowledge of appropriate reference intervals is critical not only for providing optimal clinical care, but also for enrolling children in medical research. Knowledge of normal CD4-positive T-lymphocyte parameters in this population is especially important for guiding the practice of HIV medicine in Tanzania.

Validation of an approach using only patient big data from clinical laboratories to establish reference intervals for thyroid hormones based on data mining

Effects of using an adhesive remover spray and squeezing a stress ball on pain and fear of pain during peripheral intravenous cannula removal in children aged 6-9years: A randomized controlled trial.

Onchocerciasis is endemic in 14 of Sierra Leone's 16 districts with high prevalence (47-88.5%) according to skin snips at baseline. After 11 rounds of mass treatment with ivermectin with good coverage, an impact assessment was conducted in 2017 to assess the progress towards eliminating onchocerciasis in the country. A cluster survey was conducted, either integrated with lymphatic filariasis (LF) transmission assessment survey (TAS) or standalone with the LF TAS sampling strategy in 12 (now 14) endemic districts. Finger prick blood samples of randomly selected children in Grades 1-4 were tested in the field using SD Bioline Onchocerciasis IgG4 rapid tests. In total, 17,402 children aged 4-19years in 177 schools were tested, and data from 17,364 children aged 4-14years (14,230 children aged 5-9years) were analyzed. Three hundred forty-six children were confirmed positive for Ov-16 IgG4 antibodies, a prevalence of 2.0% (95% CI 1.8-2.2%) in children aged 4-14years with prevalence increasing with age. Prevalence in boys (2.4%; 95% CI 2.1-2.7%) was higher than in girls (1.6%; 95% CI 1.4-1.9%). There was a trend of continued reduction from baseline to 2010. Using data from children aged 5-9years, overall prevalence was 1.7% (95% CI 1.5-1.9%). The site prevalence ranged from 0 to 33.3% (median prevalence = 0.0%): < 2% in 127 schools, 2 to < 5% in 34 schools and ≥ 5% in 16 schools. There was a significant difference in average prevalence between districts. Using spatial analysis, the Ov-16 IgG4 antibody prevalence was predicted to be < 2% in coastal areas and in large parts of Koinadugu, Bombali and Tonkolili Districts, while high prevalence (> 5%) was predicted in some focal areas, centered in Karene, Kailahun and Moyamba/Tonkolili. Low Ov-16 IgG4 antibody prevalence was shown in most areas across Sierra Leone. In particular, low seroprevalence in children aged 5-9years suggests that the infection was reduced to a low level after 11 rounds of treatment intervention. Sierra Leone has made major progress towards elimination of onchocerciasis. However, attention must be paid to those high prevalence focal areas.

Mobility Status as a Predictor of Obesity, Physical Activity, and Screen Time Use among Children Aged 5-11 Years in the United States

Introduction: The accurate diagnosis of thyroid disease relies on the sensitivity and specificity of laboratory tests, which require specific reference intervals. Thyroid hormone levels can be influenced by factors such as age, gender, iodine intake and geographical region. Therefore, it is recommended for clinical laboratories to establish their own reference intervals. Aim: To establish reference intervals for Thyroid Stimulating Hormone (TSH), Free Thyroxine (FT4), Anti-thyroglobulin antibody (anti-TG), and Anti-Thyroid Peroxidase Antibody (antiTPO) in males and and females. Materials and Methods: A cross-sectional study was conducted in the Department of Biochemistry, Amrita Institute of Medical Sciences (AIMS), Kochi, India, from December 2021 to July 2022. The study included 217 apparently healthy subjects aged between 18 years and 60 years. TSH, FT4, anti-TPO, and anti-TG levels were analysed to establish reference values for males and females in the two age groups: 18-40 years and 41-60 years. Reference intervals for thyroid parameters were expressed as mean±Standard Deviation (SD), median, 2.5th and 97.5th percentiles. The Mann-Whitney U test was used to assess the statistical significance of thyroid parameters between gender and age groups. Results: The mean age in the female population was 38.24±11.64 years, while in the male population, it was 39.24±10.98 years. The reference intervals and cut-offs for TSH, FT4, anti-TG and anti-TPO in females were determined as 0.80-4.12 μIU/mL, 0.99- 1.57 ngm/mL, &lt;85.33 IU/mL and &lt;45.13 IU/mL, respectively. In males, the reference intervals and cut-offs for TSH, FT4, anti-TG and anti-TPO were determined as 0.51-5.09 μIU/mL, 1.03-1.79 ng/mL, &lt;87.09 IU/mL and &lt;33.88 IU/mL, respectively. There was a significant difference in anti-TPO (p-value=0.017) in males between the two age groups. A significant difference was also observed in FT4 (p-value=0.010) and anti-TPO (p-value=0.034) between males and females. Conclusion: The study successfully established reference intervals and cut-off values for TSH, FT4, anti-TG, and antiTPO. It was found that anti-TPO levels decrease significantly with age progression. Additionally, the reference interval for TSH was wider in the 41-60 years age group compared to the younger age group.

Objective: To establish the diagnostic concentration range of urine cystatin C and the control level of urine cystatin C for patients with renal injury, and to help promote the establishment of standardization of urine cystatin C detection. Methods: 150 urine specimens and blood specimens from kidney injury patients and healthy people were collected, and stored in the refrigerator at -80°C for later use. After the specimens were collected, they were uniformly tested. Comparing the difference of blood and urine cystatin C between the kidney injury group and the healthy control group, the application value of urine cystatin C in the diagnosis and treatment of kidney injury was put forward. Results: The concentrations of cystatin C in urine and blood of renal injury group were 1.04 ± 2.14 mg/L and 1.94 ± 2.36 mg/L respectively; the concentrations of cystatin C in urine and blood of healthy control group were 0.11 ± 0.05 mg/L and 0.83 ± 0.20 mg/L respectively. The urine and blood cystatin C of the kidney injury group were significantly higher than those of the healthy control group. Compared the results of the two groups, the t values were 5.3210 and 5.7399, respectively. The P value is 0.0000; the difference is statistically significant; in comparison of urine and blood cystatin C in the kidney injury group, the value is that t = 3.4600, P = 0.0003; in comparison of urine and blood cystatin C in the healthy control group, the value is that t = 42.7744, P = 0.0000. By investigating the urine cystatin C concentration of patients with kidney injury, whether it is kidney injury or healthy controls, urine cystatin C is significantly lower than blood cystatin C. Conclusion: According to the results of this study, the concentration of urinary cystatin C in the healthy control group is 0.11 ± 0.05 mg/L. The reference interval of urinary cystatin C proposed in this study is 0.06 - 0.16 mg/L, which can be established by comprehensive multi center research. Through a multi-center study of the baseline level of urinary cystatin C in patients with renal injury, the diagnostic concentration interval of urinary cystatin C and the control level of urine cystatin C for renal injury patients were established.