Reference intervals for serum immunoglobulin A levels in Brazilian children aged 1 to 10 years: a population-based study

Abstract Objective: To determine reference intervals (Rl) for serum immunoglobulin A (IgA) levels in healthy children aged 1 to 1 0 years residing in the central region of Brazil. Methods: This cross-sectional study was conducted on 1,743 healthy children randomly selected from kindergartens and public schools in Cuiabá, MT, Brazil. The IgA RIs were defined using the statistical methods postulated by the guidelines of the United States Clinical and Laboratory Standards Institute, the nonparametric bootstrap method, and Horn's robust method after the correction of discrepancies by Tukey's, Dixon's, and Horn's methods, respectively. The results were defined based on the values contained between the 2.5th and 97.5th percentiles and their respective 95% confidence intervals. Results: Partition by sex was not necessary to determine the IgA Rl of the studied children. Homogeneous subgroups were identified among children aged 1-<2, 2-<5, and 5-<11 years, whose IgA-specific RIs were determined. Conclusion: The serum IgA RIs were established for three groups of Brazilian children aged 1-11 years, which differed from those currently applied in Brazilian pediatric practice and from those defined by international studies. This definition will help Brazilian pediatricians formulate an accurate diagnosis and facilitate decision-making.

Reference intervals for serum TSH concentrations of healthy children from the Central Region of Brazil

ABSTRACT Objective: The objective of this study was to determine the serum thyroid-stimulating hormone (TSH) concentration reference intervals (RIs) of healthy children aged 1 to 10 years of both sexes, living in the Central Region of Brazil. Subjects and methods: 1,735 children [869 (50.1%) female; 866 (49.9%) male] enrolled in the morning shift of 47 pre- and 83 public elementary schools in the municipality of Cuiabá, Mato Grosso, were studied by gathering anthropometric and social data and their medical history. A blood sample was collected from each child to determine the TSH concentration using the electrochemiluminescence method on a Cobas® 6000 modular analyzer (Analyzer series, Roche Diagnostics). Results: The RIs were determined using the 2.5 and 97.5 percentile and the mean ± 2 standard deviations methods. After identifying the homoscedastic groups by age and sex, outliers higher or lower than three standard deviations were excluded. The distribution of serum TSH concentrations showed no significant age or sex differences. Based on the percentile method, TSH RI ranged from 0.93 to 5.86 μIU/mL. Based on the mean ± 2 standard deviations, TSH RI ranged from 0.30 to 5.29 μIU/mL. Conclusion: The normal serum TSH concentration of the Brazilian children evaluated in this study differ from those of populations from other countries. Other regional population studies may validate the RIs found in this study and enable its safer use in pediatric clinical practice.

Intervalos de referencia en pediatría. Una guía de sus formas de cálculo ordenadas según su fortaleza metodológica / Pediatrics reference intervals. A guide of its calculation forms ordered according to their methodological strength

Resumen El objetivo de esta comunicación es proponer una guía de las formas decálculo de los intervalos de referencia (IR) en la población pediátrica ordenándolassegún su fortaleza metodológica. En primer lugar, el proceso recomendadopara definir un IR es el enfoque "directo", en el que se evalúanmuestras de sujetos considerados sanos. En segundo lugar, la convocatoria"indirecta", en la que a los resultados de las muestras de una base dedatos, se aplican criterios de exclusión y procesamientos estadísticos (métodosde Hoffmann y de Bhattacharya). Estos IR presentan poca diferenciacon los obtenidos por datos directos y se pueden considerar equivalentes,con la ventaja de su facilidad y sus costos más bajos. En tercer lugar, estánlos IR obtenidos de la bibliografía. La validación de los datos informadospor el fabricante es la última opción a tener en cuenta. Se reafirma laimportancia de contar con IR adecuados por sus aspectos clínicos y por laseguridad de los pacientes.

Abstract The aim of this communication is to propose a guide on the ways of calculating reference intervals (RI) in the pediatric population, ordering them according to their methodological strength. First, the recommended process to define an RI is the "direct" approach, in which samples of subjects considered healthy are evaluated. Secondly, the "indirect" approach, in which exclusion criteria and statistical processing are applied to the results ofthe samples in a database (Hoffmann and Bhattacharya methods). These RIs show little differences with those obtained by direct data and they can be considered equivalent, with the advantage of their ease and with lower costs. Thirdly, there are RIs that can be obtained from the bibliography. The validation of the data reported by the manufacturer is the last option to consider. The importance of having adequate RIs for their clinical aspects and for the safety of patients is reaffirmed.

Resumo O objetivo desta comunicação é propor um guia sobre as formas de cálculo dos intervalos de referência (IR) na população pediátrica, ordenando os mesmos de acordo com sua fortaleza metodológica. Emprimeiro lugar, o processo recomendado para definir um IR é a abordagem "direta", na qual sãoavaliadas amostras de indivíduos considerados saudáveis. Em segundo lugar, a abordagem "indireta",na qual critérios de exclusão e processamento estatístico (métodos de Hoffmann e Bhattacharya)são aplicados aos resultados das amostras em um banco de dados. Esses IR apresentam poucadiferença com os obtidos por dados diretos, podendo ser considerados equivalentes, com a vantagem de apresentarem facilidade e menor custo. Em terceiro lugar, os IR obtidos da bibliografia. A validadedos dados informados pelo fabricante é a última opção a ser considerada. A importância de termos IRadequados pelos seus aspectos clínicos e pela segurança dos pacientes é reafirmada.

Prothrombin time and activated partial thromboplastin time reference intervals in dogs, by gender and age group using the Start®4 (Stago) / Intervalos de referência para o tempo de protrombina e tempo de tromboplastina parcial ativada no cão de acordo com a idade e o gênero utilizando o Start ® 4 (Stago)

Prothrombin time (PT) and the activated partial thromboplastin time (aPTT) are useful tools for the diagnosis and monitoring of coagulation disorders in Veterinary Medicine. Our objectives were: to establish reference intervals (RI) for PT and a PTT for the dog using the Start®4 (Stago), to compare the obtained RI with literature; to evaluate the effects of gender and age on the coagulation profile. Plasma samples of 122 healthy dogs (57 males; 65 females) aged between 4 months and 18 years, divided into three age groups (0-2 years old; 3-10 years old; > 10 years old) and grouped in to males and females were analysed. The RI were estimated following the ASVCP guidelines with the Reference Value Advisor software. The RI were: PT 6.7'' to 10.8''; aPTT 9.0'' to 14.8''. PT was significantly higher in females than in males. Dogs aged 10 years or older have significantly higher mean aPTT times than younger dogs. RI comparison showed a considerable percentage of cases outside the reference RI of the literature (PT - 79.3%; aPTT - 77.1%), demonstrating the need of each laboratory to calculate its own RI. The RI established in this study are applicable for the coagulation profile assessment in dogs.

O tempo de protrombina (TP) e o tempo de tromboplastina parcial ativada (TTPa) são ferramentas úteis para o diagnóstico e monitorização das alterações da coagulação em Medicina Veterinária. Os objetivos deste estudo foram: estabelecer intervalos de referência (IR) para TP e TTPa para o cão utilizando o Start®4 (Stago), de modo a comparar os IR obtidos com a literatura; avaliar os efeitos do sexo e da idade no perfil da coagulação. Foram usadas amostras de plasma de 122 cães saudáveis (57 machos; 65 fêmeas) com idades entre quatro meses e 18 anos, divididos em três grupos (0-2 anos; 3-10 anos; > 10 anos) e agrupados em machos e fêmeas. Os IR foram calculados seguindo as diretrizes da ASVCP com o software Reference Value Advisor. Os IR obtidos foram: PT 6,7 '' a 10,8 ''; TTPa 9,0 '' a 14,8 ''. O TP foi significativamente maior nas fêmeas do que nos machos. Os cães com 10 anos ou mais apresentaram tempos médios de TTPa significativamente maiores do que cães mais jovens. A comparação de IR mostrou uma percentagem considerável de casos fora do IR de referência da literatura (TP - 79,3%; TTPa - 77,1%), confirmando a necessidade de cada laboratório calcular seu próprio IR. Os IR estabelecidos neste estudo são aplicáveis na avaliação do perfil hemostático em cães.

Verificación y transferencia de intervalos de referencia de variables bioquímicas de rutina / Verification and transfer of reference intervals of routine biochemical variables

Introducción. El correcto análisis en la interpretación de los resultados de cualquier analito biológico es esencial para la salud del paciente y está fuertemente ligado a contrastar dichos resultados con los intervalos biológicos referenciales que estén acorde a la población que está siendo analizada diariamente. El objetivo de este artículo, fue establecer intervalos referenciales (IR) en adultos para glicemia, urea, creatinina, ácido úrico, colesterol total y triglicéridos en un laboratorio clínico y comparar los valores obtenidos con los incluidos en los insertos para ese rango de edad. Metodología. La población fue de 561 adultos de ambos sexos, aparentemente sanos, que acudieron a Biomasterclin Laboratorio en Valencia, Venezuela, y cuyas edades fueron de 57,1±18,1 años. Resultados. Los IR obtenidos fueron glicemia 63,0-108,8 mg/dL, urea 17,7-54,9 mg/dL, creatinina 0,60-1,41 mg/dL, ácido úrico 0,89-7,26 mg/dL, colesterol total 78,5-251,1 mg/dL y triglicéridos 39,5-176,0 mg/dL. Los IR propuestos por la casa comercial empleada para la determinación de la glicemia y la creatinina pudieron ser transferidos a la población evaluada, mientras que el resto de los IR no. Conclusión. Debido a las diferencias que se presentan entre los IR en los estuches comerciales comparados con los de la población de individuos que acuden a los laboratorios clínicos, se hace necesario establecer IR para ser empleados en cada laboratorio clínico

The correct analysis in the interpretation of the results of any biological analyte is essential for the health of the patient and it is strongly linked to comparing those results with reference ranges that are in accordance with the population that is being analyzed on a daily basis. The objective of this study was to establish reference ranges in adults for glycemia, urea, creatinine, uric acid, total cholesterol and triglycerides in a clinical laboratory and compare the values obtained with those included in the inserts for the corresponding age group. Methodology. The population consisted of 561 apparently healthy adults of both sexes that attended Biomasterclin Laboratorio in Valencia, Venezuela, whose ages were 57.1±18.1 years. Results. The reference ranges obtained for glycemia were 63.0- 108.8 mg/dL, urea 17.7-54.9 mg/dL, creatinine 0.60-1.41 mg/dL, uric acid 0.89- 726 mg/dL, total cholesterol 78.5-251.1 mg/dL and triglycerides 39.5-176.0 mg/ dL. The reference ranges proposed by the commercial kits used for the determination of glycemia and creatinine could be transferred to the evaluated population, while the rest of the reference ranges could not. Conclusion. Due to the differences that occur between the reference ranges in commercial kits compared to those of the population of individuals who attend clinical laboratories, it is necessary to establish reference values in each clinical laboratory

Changes of new coagulation markers in healthy pregnant women and establishment of reference intervals in Changsha / 中南大学学报(医学版)

OBJECTIVES@#There is a high coagulation state in pregnant women, which is prone to coagulation and fibrinolysis system dysfunction. This study aims to explore the latest coagulation markers-thrombomodulin (TM), thrombin-antithrombin complex (TAT), plasmin-α2 plasmin inhibitor complex (PIC), and tissue plasminogen activator/plasminogen activator inhibitor compound (tPAI-C) in different stages of pregnancy, establish reference intervals (RIs) for healthy pregnant women of Chinese population, and to provide an effective and reliable reference for clinicians.@*METHODS@#A total of 492 healthy pregnant women, who underwent pregnancy examination and delivery in the Department of Obstetrics, Second Xiangya Hospital of Central South University from October 2019 to October 2020, were enrolled for this study. They were assigned into the first trimester group, the second trimester group, the third trimester group, and the puerperium group according to the pregnancy period, and 123 healthy non-pregnant women were selected as the controls. Plasma levels of TM, TAT, PIC and tPAI-C were analyzed by automatic chemiluminescence immunoassay analyzer. The RIs for TM, TAT, PIC, and tPAI-C were defined using non-parametric 95% intervals, determined following Clinical and Laboratory Standards Institute Document C28-A3c (CLSI C28-A3c), and Formulation of Reference Intervals for the Clinical Laboratory Test Items (WS/T402-2012).@*RESULTS@#TM and TAT levels increased gradually in the first, second, and third trimester women and decreased in the puerperium women (P<0.05 or P<0.01). PIC level of healthy non-pregnant women was lower than that of pregnant women (P<0.05 or P<0.01), but PIC level of pregnant and puerperium women did not differ significantly (P>0.05). tPAI-C level in healthy non-pregnant women was lower than that of pregnant women (P<0.05 or P<0.01), and tPAI-C level was significantly decreases in the puerperium women (P<0.01). The RIs for TM were as follows: Healthy non-pregnant women at 3.20-4.60 TU/mL, the first and second trimester at 3.12-7.90 TU/mL, the third trimester at 3.42-8.29 TU/mL, puerperium at 2.70-6.40 TU/mL. The RIs for TAT were as follows: Healthy non-pregnant women at 0.50-1.64 ng/mL, the first and second trimester at 0.52-6.91 ng/mL, the third trimester at 0.96-12.92 ng/mL, puerperium at 0.82-3.75 ng/mL. The RIs for PIC were as follows: Healthy non-pregnant women at 0.160-0.519 ng/mL, pregnant women at 0.162-0.770 μg/mL. The RIs for tPAI-C were as follows: Healthy non-pregnant women at 1.90-4.80 ng/mL, the first and second trimester at 2.03-9.33 ng/mL, the third trimester at 2.80-14.20 ng/mL, puerperium at 1.10-8.40 ng/mL.@*CONCLUSIONS@#The levels of 4 new coagulation markers TM, TAT, PIC, and tPAI-C in pregnant women are increased significantly during pregnancy and gradually return to normal after delivery. The RIs for TM, TAT, PIC, and tPAI-C in pregnant women by trimester are established according to CLSI C28-A3c, thus providing a clinical reference for clinician in judgement of thrombotic risk.

Establishing reference intervals of serum anti-Müllerian hormone in women of childbearing age (20-34 years old) in Henan area / 中华检验医学杂志

Objective:To analyze the serum anti-Müllerian hormone (AMH) levels in women of childbearing age in different age groups in Henan, and establish the medical reference intervals based on measurement results from this population.Methods:From January to June 2017, 620 healthy women of childbearing age (20-34 years old), who underwent pre-pregnancy eugenics and pre-marital checkups in 13 project sites in Henan, were included in this study. Participants were divided into 3 age groups: 20-24 years group ( n=210), 25-29 years group ( n=207), and 30-34 years group ( n=203). Spearman correlation coefficient was used to evaluate the correlation between serum AMH level and age; Kruskal-Wallis H test was used to compare the serum AMH levels of different age groups; Wilcoxon test was used for comparison between pairs; the percentile method ( P2.5, P97.5) was used to establish medical reference interval of serum AMH in women of childbearing age for the whole population and different age groups, respectively. Results:The correlation coefficient between serum AMH and age in women of childbearing age (20-34 years old) is -0.17 ( P<0.001). There was a statistically significant difference in the overall frequency distribution of serum AMH levels among the three different age groups ( H=21.978, P<0.05). Among them, there is a statistically significant difference between the 20-24 years group and the 30-34 years group ( Z=4.292, P<0.05). There is a statistically significant difference between the 25-29 years group and the 30-34 years group ( Z=3.803, P<0.05). The reference range of serum AMH is 0.281-9.693 μg/L in this cohort; the reference range of serum AMH is 0.524-10.760, 0.229-9.200, 0.115-8.200 μg/L for women of childbearing age at 20-24, 25-29 and 30-34 years, respectively. Conclusion:The serum AMH level of women of childbearing age (20-34 years old) decreases with age. It is of great significance to establish the serum AMH reference interval for women of childbearing age in different age groups in Henan.

Thyroid hormones reference ranges during each trimester of normal pregnancy subjects in Andhra Pradesh, South India

Background: The Thyroid hormones normal levels are very much essential for fetal neural development and good pregnancy outcome. Thyroid insufficiency during pregnancy may be associated with adverse obstetric outcome and fetal neurodevelopmental deficits. The main objective of the study is to estimate and establish the reference ranges of thyroid hormones as it varies from place to place and inter dependent on the iodine levels as the American Thyroid Association strongly recommends to refer to population defined trimester-specific reference ranges.Methods: A longitudinal study was conducted at obstetric clinic, Kakinada city, Andhra Pradesh over a period of 18 months. The total number of normal pregnancy subjects included in this study was 126. Thyroid hormones estimation was done by Competitive electrochemiluminescence (T3 and T4) and Sandwich electrochemiluminescence (TSH) at Thyorocare Laboratory. Only 47 subjects were having all three trimester thyroid hormone levels estimated during each trimester and were followed up to full term. The 2.5th and 97.5th percentiles were calculated as the reference intervals for thyroid hormone levels during each trimester.Results: The thyroid hormone levels during first, second and third trimesters median with reference intervals - Total Triiodothyronine (T3) : 163(100.2-230), 168(121-219.2), 168(110.2-222.6) ng/dl ,Total Thyroxine (T4) : 8.4(4.05-16.64) , 10.2(4.09-18.7), 11.2(3.8-16.7) μg/dl and Thyroid Stimulating Hormone (TSH ):2.52(1.6-7.9) 3.01(1.28-7.6) 3(1.5-8.4) μIU/mlConclusions: The trimester-specific reference intervals and median for thyroid hormones during normal pregnancy have been established for pregnant South Indian women in Andhra Pradesh by full term follow-up during pregnancy using 2.5th and 97.5th percentiles and median.

Transferencia de intervalos de referencia en Valencia-Venezuela / Transference of reference intervals in Valencia-Venezuela / Transferência de intervalos de referência em Valência-Venezuela

El objetivo de la presente investigación consistió en revisar si los valores de referencia producidos por la industria de diagnóstico in vitro eran transferibles a una determinada población. Para este estudio fueron analizadas muestras de suero de una población de 23 individuos. El análisis de las muestras estudiadas fue realizado mediante el método de colorimetría usando equipos Rx Daytona. Los analitos determinados para el estudio fueron glucemia, colesterol, triglicéridos por método enzimático y creatinina por método cinético, empleando el kit de reactivos de la misma casa comercial del instrumento. Para la evaluación y análisis estadístico de los datos fue empleado el logaritmo de decisión propuesto por Ventimiglia y Fink en 2002. Como resultado se obtuvieron porcentajes de transferibilidad de 100% para la totalidad de los analitos. De acuerdo con los resultados obtenidos, se dieron por verificados y se aceptó la transferibilidad de los intervalos de referencia comerciales para la población en estudio.

The aim of this investigation was to review if the reference values produced by the in vitro diagnostic industry were transferable to a specific population; for the study, serum samples from a population of 23 individuals were analyzed.The analysis of the samples was carried out using the colorimetric method with Rx Daytona equipment. The analytes determined for the study were glycemia, cholesterol, triglycerides by enzymatic method and creatinine by kinetic method, using the reagent kit from the same commercial brand of said equipment. The statistical analysis was done applying the decision logarithm proposed by Ventimiglia F and Fink N (2002). As a result, percentages of 100% of transferability were found on all the analytes. According to the results obtained, the transferability of the commercial reference intervals for the population under study was accepted.

O objetivo da presente investigação foi revisar se os valores de referência produzidos pela indústria de diagnóstico in vitro eram transferíveis para uma população específica. Para esse estudo amostras de soro foram analisadas de uma população de 23 indivíduos. A análise das amostras estudadas foi realizada utilizando o método de colorimetria, utilizando equipamentos Rx Daytona. Os analitos determinados para o estudo foram glicemia, colesterol, triglicerídeos pelo método enzimático e creatinina pelo método cinético, utilizando o kit de reagentes da mesma casa comercial do instrumento. Para a avaliação e análise estatística dos dados foi utilizado o logaritmo de decisão proposto por Ventimiglia F e Fink N 2002. Como resultados, percentuais de transferibilidade de 100% foram obtidos para todos os analitos. De acordo com os resultados obtidos, foram tidos como verificados e se aceita a transferibilidade dos intervalos de referência comerciais para a população em estudo.

Proposition of decision limits for serum lipids in Brazilian children aged one to 13 years / Proposição de limites de decisão dos lipídeos séricos para crianças brasileiras de um a 13 anos de idade

Abstract Objective: To determine decision limits for total cholesterol, LDL-cholesterol, non-HDL cholesterol, HDL-cholesterol, and triglycerides in healthy children and adolescents from Cuiabá, Brazil. Methods: This was a cross-sectional study of 1866 healthy children and adolescents randomly selected from daycare centers and public schools in Cuiabá. The desirable levels of serum lipids were defined using the classic criteria, i.e., total cholesterol, LDL-cholesterol, non-HDL cholesterol, and triglycerides levels below the P75 percentile, and HDL-c above the P10 percentile. Results: For CT, P75 was: 160 mg/dL for the age range of 1 to <3 years, 170 mg/dL for ≥3 to <9 years, and 176 mg/dL for ≥9 to <13 years. For non-HDL cholesterol, it was 122 mg/dL for the age range of 1 to <13 years. For LDL-c, it was 104 mg/dL at the age range of 1 to <9 years and 106 mg/dL from ≥9 to <13 years. For TG, it was 127 mg/dL from 1 to <2 years; 98 mg/dL from ≥2 to <6 years; and 92 mg/dL from ≥6 to <13 years. As for HDL-cholesterol, P10 was 24 mg/dL, 28 mg/dL, 32 mg/dL, and 36 mg/dL, for the age ranges of 1 to <2 years, ≥2 to <3 years, ≥3 to <4 years, and ≥4 to <13 years, respectively. Conclusion: The decision limits for the serum lipid levels defined in this study differed from those observed in the current Brazilian and North-American guidelines, especially because it differentiates between the age ranges. Using these decision limits in clinical practice will certainly contribute to improve the diagnostic accuracy for dyslipidemia in this population group.

Resumo Objetivo: Determinar limites de decisão (LD) para o colesterol total (CT), LDL-colesterol (LDL-c), colesterol não-HDL (c-NHDL), HDL-colesterol (HDL-c) e triglicérides (TG) em crianças e adolescentes saudáveis de Cuiabá. Método: Estudo transversal envolvendo 1.866 crianças e adolescentes saudáveis de creches e escolas municipais públicas de Cuiabá, aleatoriamente selecionadas. Os LD desejáveis dos lipídeos séricos foram definidos pelos critérios clássicos, isto é, níveis de CT, LDL-c, c-NHDL, TG abaixo do percentil 75, e de HDL-c acima do percentil 10. Resultados: Os P75 para CT foram: 160 mg/dL para a faixa etária de 1 a < 3 anos, 170 mg/dL para ≥ 3 a < 9 anos e 176 mg/dL para ≥ 9 a < 13 anos. Para o c-NHDL, de 122 mg/dL na faixa etária de 1 a < 13 anos. LDL-c: 104 mg/dL na faixa etária de 1 a < 9 anos e 106 mg/dL de ≥ 9 a < 13 anos. TG: 127 mg/dL entre 1 a < 2 anos; 98 mg/dL de ≥ 2 a < 6 anos; e 92 mg/dL de ≥ 6 a < 13 anos. Quanto ao HDL-c, o P10, foi de 24 mg/dL, 28 mg/dL, 32 mg/dL e 36 mg/dL, para as faixas etárias de 1 a < 2 anos, ≥ 2 a < 3 anos, ≥ 3 a < 4 anos e ≥ 4 a < 13 anos, respectivamente. Conclusão: Os LD dos níveis séricos de lipídeos definidos neste estudo diferem daqueles apresentados nas diretrizes brasileiras e americanas atuais, especialmente por fazer a diferenciação entre as idades. Utilizar tais LD em nossa prática clínica certamente contribuirá para melhorar a acurácia do diagnóstico de dislipidemia nesse grupo populacional.

Alkaline phosphatase: reference interval transference from CALIPER to a pediatric Brazilian population / Fosfatase alcalina: transferência de intervalos de referência do CALIPER para uma população pediátrica brasileira

ABSTRACT Introduction: Interpreting laboratory tests requires reference intervals (RI) that may vary between different populations. For the diagnosis of hypophosphatasia (HPP), lower limits of alkaline phosphatase (ALP) levels must be determined. Objective: To transfer the RI findings for ALP obtained by the Canadian Laboratory Initiative in Pediatric Reference Intervals (CALIPER) in children and adolescents, adjusted for the Brazilian population. Methods: The ALP measures from 1690 subjects (aging from 1-18 years) were analyzed. The CALIPER subgroups and the Clinical and Laboratory Standards Institute (CLSI) guideline were used for validation. Inclusion criteria were patients with normal range of hepatic and renal function, bone metabolism, and blood counts. Exclusion criteria were hospitalization, low weight, and use of drugs that could interfere in the ALP measurement and patients in with more than three orders for ALP measuring test. The RI obtained were considered valid if more than 90% of patients were whitin of the CALIPER RI. Results: The ALP RI results (IU/l) obtained were: 149-301 for both sexes aged 1-9 years; 127-326 for both sexes aged 10-12 years; 62-212 for girls and 129-437 for boys aged 13-14 years; 52-120 for girls and 78-268 for boys aged 15-16 years; 45-97 for girls and 40-129 for boys aged 17-18 years. In 92.4% of the patients, the results were comparable with those of the CALIPER study. Conclusion: The results demonstrated that the ALP RI for Brazilian children and adolescents are comparable to the CALIPER study in 92.4% of the patients and can be used for this population.

RESUMO Introdução: A interpretação de exames laboratoriais necessita de intervalos de referência (IR) que podem variar entre diferentes populações. Para o diagnóstico de hipofosfatasia, deve-se determinar limites inferiores do IR da fosfatase alcalina (FA). Objetivo: Transferir os resultados de IR da FA obtidos pela Canadian Laboratory Initiative in Pediatric Reference Intervals (CALIPER) em crianças e adolescentes, ajustados para a população brasileira. Métodos: Analisaram-se as dosagens de FA de 1690 indivíduos (1 a 18 anos). Subgrupos do CALIPER e diretrizes do Clinical and Laboratory Standards Institute (CLSI) foram utilizados. Os critérios de inclusão foram pacientes com função hepática, renal, exames do metabolismo ósseo e hemograma normais; já os de exclusão, hospitalização, baixo peso, uso de drogas interferentes na dosagem de FA e pacientes com mais de três solicitações de FA. Os IR seriam considerados válidos se mais de 90% dos pacientes se encontrassem dentro dos IR do CALIPER. Resultado: Os resultados dos IR de FA (UI/l) obtidos foram: 149-301 para ambos os sexos entre 1-9 anos; 127-326 para ambos os sexos entre 10-12 anos; 62-212 para meninas e 129-437 para meninos entre 13-14 anos; 52-120 para meninas e 78-268 para meninos entre 15-16 anos; 45-97 para meninas e 40-129 para meninos entre 17-18 anos de idade. Em 92,4% dos pacientes os resultados eram comparáveis com os do CALIPER. Conclusão: Os resultados demonstraram que os IR de FA para crianças e adolescentes brasileiras são comparáveis com o estudo CALIPER em 92,4% dos pacientes e podem ser utilizados para essa população.

Complete Blood Count Reference Intervals and Patterns of Changes Across Pediatric, Adult, and Geriatric Ages in Korea

BACKGROUND: Sampling a healthy reference population to generate reference intervals (RIs) for complete blood count (CBC) parameters is not common for pediatric and geriatric ages. We established age- and sex-specific RIs for CBC parameters across pediatric, adult, and geriatric ages using secondary data, evaluating patterns of changes in CBC parameters. METHODS: The reference population comprised 804,623 health examinees (66,611 aged 3–17 years; 564,280 aged 18–59 years; 173,732 aged 60–99 years), and, we excluded 22,766 examinees after outlier testing. The CBC parameters (red blood cell [RBC], white blood cell [WBC], and platelet parameters) from 781,857 examinees were studied. We determined statistically significant partitions of age and sex, and calculated RIs according to the CLSI C28-A3 guidelines. RESULTS: RBC parameters increased with age until adulthood and decreased with age in males, but increased before puberty and then decreased with age in females. WBC and platelet counts were the highest in early childhood and decreased with age. Sex differences in each age group were noted: WBC count was higher in males than in females during adulthood, but platelet count was higher in females than in males from puberty onwards (P < 0.001). Neutrophil count was the lowest in early childhood and increased with age. Lymphocyte count decreased with age after peaking in early childhood. Eosinophil count was the highest in childhood and higher in males than in females. Monocyte count was higher in males than in females (P < 0.001). CONCLUSIONS: We provide comprehensive age- and sex-specific RIs for CBC parameters, which show dynamic changes with both age and sex.

Reference intervals of thyroid hormones during pregnancy in Korea, an iodine-replete area

BACKGROUND/AIMS: Maternal thyroid dysfunction has been associated with adverse pregnancy outcomes. The purpose of our study was to establish trimester-specific reference intervals for thyroid hormones in pregnant women in Korea, where iodine intake is more than adequate and to examine pregnancy and perinatal outcomes in their offspring. METHODS: Among 459 healthy pregnant women who were screened, we enrolled 417 subjects who had negative results for thyroid autoantibodies. Serum thyroid stimulating hormone (TSH) and free thyroxine were measured using an immunoradiometric assay. Urine iodine concentration was measured using inductively coupled plasma-mass spectrometry in 275 women. Reference ranges of thyroid hormones were determined according to the guidelines of the National Academy of Clinical Biochemistry. Pregnancy and perinatal outcomes were compared according to maternal thyroid function. RESULTS: The reference ranges of serum TSH were 0.03 to 4.24 mIU/L in the first trimester, 0.13 to 4.84 mIU/L in the second trimester, and 0.30 to 5.57 mIU/L in the third trimester. Pregnancy and perinatal outcomes did not vary in mothers with subtle changes in thyroid function. CONCLUSIONS: Trimester-specific thyroid hormone reference intervals in Korean pregnant women differ from those of other countries with different iodine nutrition status and ethnicity. The establishment of population-based, reliable trimester-specific reference intervals is critical for the interpretation of thyroid function in pregnant women to avoid unnecessary tests and treatments.

Quality Requirements for Reference Intervals and Decision Limits in Clinical Laboratory / 现代检验医学杂志

Reference intervals and decision limits are critical parts of the clinical laboratory report.The evaluation ot their correct use represents a tool to verify the post analytical quality.Four elements are identified as indicators:① The use of decision limits for lipids and glycated hemoglobin.② The use of common reference values.③The presence of gender-related reference intervals for at least the following common serum measurands (besides obviously the fertility relate hormones):alkaline phosphatase (ALP),alanine aminotransferase (ALT),creatine kinase (CK),creatinine,gamma-glutamyl transferase (GGT),IgM,ferritin,iron,transferrin,urate,red blood cells (RBC),hemoglobin (Hb) and hematocrit (HCT).④) The presence of age-related reference intervals.The problem of specific reference intervals for elderly people is discussed,but their use is not recommended.On the contrary it is necessary the presence of pediatric age-related reference intervals at least for the following common serum measurands:ALP,amylase,creatinine,inorganic phosphate,lactate dehydrogenase,aspartate aminotransferase,urate,insulin like growth factor 1,white blood cells,RBC,Hb,HCT,alfafetoprotein and fertility related hormones.The lack of such reference intervals may imply significant risks for the patients.

Establishment of reference range of serum thyroid hormone in women with different gestational age in Wu-han area / 实用医学杂志

Objective To establish the laboratory and geography-specific reference intervals for thyroid hormones during pregnancy and changes of serum thyroid hormone in Wuhan. Methods According to NACB guidelines,a total of 1 186 female including in or without pregnancy were recruited in our hospital randomly when they came to routine antenatal clinic. The 2.5 th and 97.5 th percentiles were calculated as the reference intervals for specialty of serum thyroid function including serum thyroid stimulating hormone(TSH),serum free three io-dine thyroid(FT3),serum free thyroxine(FT4)levels during each trimester by chemiluminescence.Results On comparing to non-pregnant women,the serum thyroid hormone in pregnant women had significant difference as the following:(1)FT3 concentrations showed decreased median centile throughout gestation step by step;(2)FT4 lev-els in second and third trimester had slightly decreased;(3)TSH levels had significant decreased in first and sec-ond trimeste and had no significant difference between the early pregnancy and middle pregnancy,and had recoved to the similar level of before pregnancy in middle pregnancy and late pregnancy.Compared with control group,the serum thyroid function levels of pregnant women had significant differences in trimesters. There were 5.84%, 19.09% and 28.91% of women in the first,second and third trimester,respectively,with serum TSH higher than the upper reference limit,or lower than the lower reference limit.Conclusions Serum thyroid function had signifi-cant correlations with pregnancy in Wuhan area. To establish pregnancy-specific thyroid function reference inter-vals of local area can reduce underdiagnosis effectively in thyroid gland related diseases.

The analysis of the reference intervals of lipid metabolism indexes and dyslipidaemia among the adults of Tibetan in Ganzi County / 国际检验医学杂志

Objective To investigate the reference intervals of lipid metabolism indexes and dyslipidaemia situation among the a-dult of Tibetan in Ganzi County .Methods The serum samples were collected from 661 healthy subjects in Ganzi county ,total cho-lesterol(TC) ,triglyceride(TG) ,high density lipoprotein cholesterol(HDL-C) ,low density lipoprotein cholesterol(LDL-C) ,apoli-poprotein A1(ApoA1) and apolipoprotein B(ApoB) levels were measured .According to the American Society for Clinical Laborato-ry Standards(CLSI) C28-A3 documentation and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) guidelines for establishing of reference interval with reasonable method and reliable basis ,the interval value of this lipid metabolism indexes were calculated .The dyslipidemia situation was analyzed based on "The Guideline of Prevention and Treatment of Dyslipi-demia in Chinese Adults in 2007".Results In these population ,TG ,LDL-C and ApoB in the serum of male were higher than those of female ,while HDL-C and ApoA1 were lower than those of female ,the difference was statistically significant (P<0 .05) .TC , LDL-C and TG level had a change tendency with ages obviously ,while the changes of HDL-C ,ApoA1 and ApoB metabolism level were not inconspicuous .In this population ,TC ,LDL and ApoB reference intervals were 2 .75 -6 .82 mmol/L ,1 .36 -4 .3 mmol/L and 0 .24-1 .38 mmol/L respectively .The reference interval of TG ,LDL-C and ApoA1 in male population were 0 .5-2 .36 mmol/L ,0 .9-1 .93 mmol/L and 0 .82-1 .87 mmol/L respectively ,meanwhile ,the reference range of TG ,HDL-C and ApoA1 in female population were 0 .47-3 .19 mmol/L ,0 .96-2 .19 mmol/L and 0 .94-2 .02 mmol/L respectively .The incidence of dyslipidemia in Tibetan adults was high ,the incidence of hypercholesterolemia ,hypertriglyceridemia ,mixed hyperlipidemia and low high-density lip-oprotein were 32 .07% ,21 .18% ,12 .86% and 6 .51% respectively .Conclusion In this research ,we established the reference inter-val of blood lipid metabolism indexes of Tibetan adults in Ganzi county and analyzed the incidence of hyperlipidemia in this popula-tion initially .This results provide reference data for clinical intervention treatment of patients with hyperlipidemia in Tibetan popu-lation in Ganzi area ,which is helpful for guiding the prevention and treatment of dyslipidemia in this region .

Reference intervals for plasma presepsin in healthy elderly adults / 国际检验医学杂志

Objective To establish the reference intervals(RIs) for plasma presepsin in healthy population.Methods The document C28-A3 issued by CLSI was a guideline about how to define,establish,and verify reference intervals in the clinical laboratory.Plasma values were determined with CLEIA for 1 250 healthy adults(aged 20-90 years old),including 624 males and 626 females.The central 95 percentile of RIs were determined using nonparametric statistical methods.Results The presepsin values in elderly population showed a Gaussian distribution and age/sex related changes.The RIs for plasma presepsin in the reference population respective of age(ranged from 20-＜30,30-＜ 60,60-＜ 90 years) were 50-195,47-170,41-142 pg/mL for males and 43-173,44-162,38-137 pg/mL for females respectively.Conclusion The RIs for plasma presepsin were established according to the gender and age groups in the healthy adults,and could provide a reference for the clinical and laboratory.

The analysis of the reference intervals of lipid metabolism indexes and dyslipidaemia among the adults of Tibetan in Ganzi County / 国际检验医学杂志

Objective To investigate the reference intervals of lipid metabolism indexes and dyslipidaemia situation among the a-dult of Tibetan in Ganzi County .Methods The serum samples were collected from 661 healthy subjects in Ganzi county ,total cho-lesterol(TC) ,triglyceride(TG) ,high density lipoprotein cholesterol(HDL-C) ,low density lipoprotein cholesterol(LDL-C) ,apoli-poprotein A1(ApoA1) and apolipoprotein B(ApoB) levels were measured .According to the American Society for Clinical Laborato-ry Standards(CLSI) C28-A3 documentation and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) guidelines for establishing of reference interval with reasonable method and reliable basis ,the interval value of this lipid metabolism indexes were calculated .The dyslipidemia situation was analyzed based on "The Guideline of Prevention and Treatment of Dyslipi-demia in Chinese Adults in 2007".Results In these population ,TG ,LDL-C and ApoB in the serum of male were higher than those of female ,while HDL-C and ApoA1 were lower than those of female ,the difference was statistically significant (P<0 .05) .TC , LDL-C and TG level had a change tendency with ages obviously ,while the changes of HDL-C ,ApoA1 and ApoB metabolism level were not inconspicuous .In this population ,TC ,LDL and ApoB reference intervals were 2 .75 -6 .82 mmol/L ,1 .36 -4 .3 mmol/L and 0 .24-1 .38 mmol/L respectively .The reference interval of TG ,LDL-C and ApoA1 in male population were 0 .5-2 .36 mmol/L ,0 .9-1 .93 mmol/L and 0 .82-1 .87 mmol/L respectively ,meanwhile ,the reference range of TG ,HDL-C and ApoA1 in female population were 0 .47-3 .19 mmol/L ,0 .96-2 .19 mmol/L and 0 .94-2 .02 mmol/L respectively .The incidence of dyslipidemia in Tibetan adults was high ,the incidence of hypercholesterolemia ,hypertriglyceridemia ,mixed hyperlipidemia and low high-density lip-oprotein were 32 .07% ,21 .18% ,12 .86% and 6 .51% respectively .Conclusion In this research ,we established the reference inter-val of blood lipid metabolism indexes of Tibetan adults in Ganzi county and analyzed the incidence of hyperlipidemia in this popula-tion initially .This results provide reference data for clinical intervention treatment of patients with hyperlipidemia in Tibetan popu-lation in Ganzi area ,which is helpful for guiding the prevention and treatment of dyslipidemia in this region .

Reference intervals for plasma presepsin in healthy elderly adults / 国际检验医学杂志

Objective To establish the reference intervals(RIs) for plasma presepsin in healthy population.Methods The document C28-A3 issued by CLSI was a guideline about how to define,establish,and verify reference intervals in the clinical laboratory.Plasma values were determined with CLEIA for 1 250 healthy adults(aged 20-90 years old),including 624 males and 626 females.The central 95 percentile of RIs were determined using nonparametric statistical methods.Results The presepsin values in elderly population showed a Gaussian distribution and age/sex related changes.The RIs for plasma presepsin in the reference population respective of age(ranged from 20-＜30,30-＜ 60,60-＜ 90 years) were 50-195,47-170,41-142 pg/mL for males and 43-173,44-162,38-137 pg/mL for females respectively.Conclusion The RIs for plasma presepsin were established according to the gender and age groups in the healthy adults,and could provide a reference for the clinical and laboratory.

Verification and establishment of reference value ranges of blood cells analysis among adults in Changsha City / 国际检验医学杂志

Objective To verify the indicator reference value ranges of blood cells analytic report by quoting the WS/T 405-2012 industry standard in Changsha area and to establish the reference value ranges of research parameters suitable for local area.Methods The blood cells analytic results in 3138 cases of reference group were analyzed according to the program of the Formulation of Reference Intervals in Clinical Laboratory Detection Items and the results were compared with the WS/T 405-2012 industry standard.Results WBC,Neu#,Mon%,MCHC,PLT,MPV,PCT,P-LCC,P-LCR and InR‰ in the report parameters and WBC-D,PDW-SD in the research parameters had no statistical differences between males and females(P>0.050);WBC,Neu#,Mon%,MCHC and PLT had no difference between genders,the indicators were narrowed compared with the reference value ranges in standard;the reference value ranges of Neu%,RBC,HGB,MCV and MCH in the male blood cells analytic indicators were narrowed,the lower limits of Bas%,Lym#,Mon# and HCT reference value ranges were elevated,the upper limits of Bas%,Lym#,Mon# and HCT reference value ranges were elevated,while the upper limits of Eos# and Eos% reference value ranges were decreased,the Lym% lower limit was decreased;Neu%,Lym#,Mon# and RBC in the female blood cells analytic indicators were narrowed,the lower limits of Bas# and Bas% were increased,the lower limits of Eos%,Lym%,HGB,MCV and MCH were decreased,the upper limits of Eos#,Eos%,Lym%,HGB,MCV and MCH were decreased and the HCT upper limit was elevated.Conclusion The Changsha area should have the reference value ranges of selective quoted standards and establishes the reference value ranges suitable for local area or laboratory.