Cross-Method Comparison of Serum Androstenedione Measurement Using Three Different Assays: The Siemens Immulite Immunoassay, the Roche Elecsys Immunoassay, and an LC/MS-MS Assay

Abstract Introduction: Androstenedione is a common precursor of male and female sex hormones produced by the adrenal glands and gonads. Serum androstenedione is a helpful biomarker in the diagnostic workup of a subset of patients with polycystic ovary syndrome (PCOS), the investigation of virilizing endocrinopathies, and for monitoring pediatric patients with congenital adrenal hyperplasia. The gold standard for the measurement of androstenedione is LC-MS/MS. A newly developed androstenedione competitive immunoassay is now available in the US, the Roche Elecsys Androstenedione (ASD) immunoassay. Until recently, the Siemens Immulite assay was the only non-radioimmunologic immunoassay available. We characterized the analytical and clinical performance of the ASD across different patient populations and in comparison to the Immulite and an LC-MS/MS assay. Methods and materials: The experiments performed were: linearity and analytical measuring range (AMR), precision (intra- and inter-assay), and accuracy. Androstenedione was measured on de-identified residual serum samples (n=40) using the ASD and Immulite immunoassays and an LC-MS/MS assay. The reference intervals (RIs) provided by Roche for healthy male (0.280-1.52 ng/mL), healthy female (0.490-1.31 ng/mL), postmenopausal women (0.187-1.07 ng/mL), healthy children (<0.519 ng/mL), and patients with PCOS (0.645-3.47 ng/mL) were verified with at least 20 specimens, according to CLSI C28A3. Statistical analysis was performed using EP Evaluator and R program. Results: The ASD had a linear response across the AMR of 0.3 to 10.0 ng/mL. The inter- and intra-assay coefficients of variation were 4.5% and 2.0% or lower, at concentrations 0.5-6.7 ng/mL, respectively. The ASD and LC-MS/MS assays had a mean bias of -0.0542 ng/mL (-2%), Deming regression of y = 1.000 [0.961; 1.039] x - 0.0548 [-0.1806; 0.0709], and r = 0.9930. The Immulite assay had a mean bias of 1.15 ng/mL (44%) and 1.22 ng/mL (32%) compared to the LC-MS/MS and ASD assays, respectively. The recommended RIs from Roche for healthy male, female, and postmenopausal female groups were successfully verified in our patient population. However, the androstenedione concentrations for the healthy children and PCOS groups were outside of the suggested RIs, with concentrations up to 1.41 ng/mL and 0.527-2.24 ng/mL, respectively. Unlike published elsewhere, hormone therapies such as contraceptive pills and steroid treatments did not significantly affect serum androstenedione concentrations in healthy females and patients with PCOS. Conclusion: The ASD is superior to the Immulite immunoassay, and it has excellent comparability with the LC-MS/MS for serum androstenedione measurement. The RIs published by Roche may not be universally transferable; verification is recommended, and establishing RIs for the pediatric population may be necessary.

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Comparison of three serum androstenedione assays: the Siemens Immulite immunoassay, the Roche Elecsys immunoassay, and an LC-MS/MS assay

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqab189.017 ◽

2021 ◽

Vol 156 (Supplement_1) ◽

pp. S10-S11

Author(s):

Ruhan Wei ◽

Kathleen Bowers ◽

Grace Kroner ◽

Drew Payto ◽

Jessica Colón-Franco

Keyword(s):

Clinical Performance ◽

Polycystic Ovary ◽

Method Comparison ◽

Clinical Information ◽

Reference Intervals ◽

Female Group ◽

Healthy Children ◽

Oral Contraceptive Pills ◽

Contraceptive Pills ◽

Healthy Female

Abstract Introduction Serum androstenedione (ASD) is a useful biomarker in the diagnostic workup of hyperandrogenism, congenital adrenal hyperplasia, premature adrenarche, and polycystic ovary syndrome (PCOS). Recently, the Elecsys ASD assay (Roche Diagnostics), a competitive electrochemiluminescence immunoassay, became available in the US. Herein, the analytical and clinical performance of the Elecsys ASD assay was tested and compared with the Immulite assay (our current assay) and an LC-MS/MS assay (the gold standard) using deidentified residual patient specimens. Method In this study, the linearity, analytical measuring range (AMR), precision, and accuracy of the Elecsys ASD assay (cobas e602 analyzer) were tested. ASD from 40 deidentified residual serum/plasma samples was measured and compared between the Elecsys assay, the Immulite assay, and an LC-MS/MS assay. The reference intervals (RIs) provided by Roche for healthy male (0.280-1.52 ng/mL), healthy female (0.490-1.31 ng/mL), postmenopausal female (0.187-1.07 ng/mL), healthy children (<0.519 ng/mL), and patients with PCOS (0.645-3.47 ng/mL) were tested with at least 20 specimens, according to CLSI C28A3. Statistical analysis was performed using EP evaluator and R program. Result and conclusion The assay had a linear response across the AMR (0.3-10.0 ng/mL). The inter- and intra-assay coefficients of variation measured at multiple concentrations were less than 4.5% and 2.0%, respectively. The Elecsys ASD assay had an excellent correlation with the LC-MS/MS assay with a mean bias of -0.0542 ng/mL (-2%). The Immulite assay had a mean bias of 1.15 ng/mL (44%) and 1.22 ng/mL (32%) compared to the LC-MS/MS and Elecsys ASD assays, respectively. The Roche recommended RIs for healthy males and postmenopausal females were successfully verified in our patient population. However, the ASD concentrations for the healthy children were outside of the suggested RI, with concentrations up to 1.41 ng/mL. Therefore, the RIs for healthy children were adopted from RIs established using the same LC-MS/MS method used for method comparison. RI verification for the healthy female group also failed since many low ASD values were observed. Instead, a RI of < 1.30 ng/mL was established using 60 deidentified residual serum/plasma specimens. Finally, a separate RI for the PCOS group was not established since it may not provide useful clinical information due to the heterogeneity of the group. Unlike some published studies, hormone therapies such as oral contraceptive pills did not cause a significant decrease in ASD in patient specimens (p=0.4967). Overall, the Elecsys ASD assay has superior comparability to the LC-MS/MS assay than the Immulite assay. We were unable to verify the applicability of the RIs recommended by Roche for healthy females and children, warranting the need to establish or transfer them. When RI verification is challenging due to limited qualified specimens, transferring from an LC-MS/MS established RI is possible as long as the methods are comparable.

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Age- and sex-specific reference intervals for the serum cystatin C/creatinine ratio in healthy children (0–18 years old)

Journal of International Medical Research ◽

10.1177/0300060519855575 ◽

2019 ◽

Vol 47 (7) ◽

pp. 3151-3159 ◽

Cited By ~ 2

Author(s):

Changjin Liu ◽

Jing Wen ◽

Jialin Xiang ◽

Xuhong Ouyang ◽

Yan Yang ◽

...

Keyword(s):

Cystatin C ◽

Pediatric Population ◽

Age Groups ◽

Serum Markers ◽

Reference Intervals ◽

Specific Reference ◽

Healthy Children ◽

Serum Samples ◽

Serum Cystatin C ◽

Age And Sex

Objective This study aimed to investigate serum levels of the cystatin C (CysC)/creatinine (Cr) ratio and renal serum markers (CysC, Cr, urea, and uric acid [UA]) for different ages and by sex. We also aimed to establish pediatric reference intervals for the serum CysC/Cr ratio. Methods Serum samples were collected from 4765 healthy children (0–18 years old). Serum markers of renal function were measured, and the CysC/Cr ratio of each participant was calculated and statistically analyzed. Results The renal marker CysC did not substantially change after 1 year old. Cr, urea, and UA levels generally increased with age. However, the serum CysC/Cr ratio steadily decreased with age. The CysC/Cr ratio showed significant differences in age among all age groups and varied with sex, except for in the 1 to 6-year-old groups. The overall serum CysC/Cr ratio in girls was higher than that in boys. Conclusion Reference intervals of the serum CysC/Cr ratio in the pediatric population were established. These intervals need to be partitioned by age and sex.

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Normative Values of High-Sensitivity Cardiac Troponin T and N-Terminal pro-B-Type Natriuretic Peptide in Children and Adolescents: A Study from the CALIPER Cohort

The Journal of Applied Laboratory Medicine ◽

10.1093/jalm/jfaa090 ◽

2020 ◽

Author(s):

Emily Lam ◽

Victoria Higgins ◽

Liyong Zhang ◽

Man Khun Chan ◽

Mary Kathryn Bohn ◽

...

Keyword(s):

Children And Adolescents ◽

Natriuretic Peptide ◽

Cardiac Troponin ◽

Troponin T ◽

Pediatric Population ◽

High Sensitivity ◽

Reference Intervals ◽

Normative Values ◽

Healthy Children ◽

Serum Samples

Abstract Background Cardiac troponin (cTn) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are increasingly used clinically to evaluate and prognosticate acute myocardial infarction and heart failure, respectively. Pediatric reference intervals and cut-offs have not been established for Roche’s Elecsys Troponin T hs (high sensitive) assay. Although pediatric reference intervals exist for NT-proBNP, cut-off values do not exist. In this study, we report reference intervals and 99th percentile cut-offs in a large, healthy Canadian pediatric population using the CALIPER cohort. Methods Blood samples from 484 healthy children and adolescents between 0 and <19 years old were recruited from hospital outpatient clinics and community settings. Serum samples were analyzed using Roche’s Cobas e411 and evaluated for high-sensitivity cTnT (hs-cTnT) and NT-proBNP concentrations. 95% reference intervals and 99th percentile cut-off values were established. Results Three hs-cTnT age partitions were established (0 to <6 months, 6 months to <1 year, and 1 to <19 years) with highest concentrations observed in children under 1 year. Two NT-proBNP age partitions were established (0 to <1 year, and 1 to <19 years), also with higher concentrations in infants under 1 year of age. For each of these age partitions, the 99th percentile cut-off, 95% reference interval, and proportion of detectable concentrations were determined. Conclusions This is the first study to examine hs-cTnT and NT-proBNP reference values together in a healthy pediatric cohort without other clinical indications. We present 99th percentile cut-offs, which will allow clinicians to appropriately evaluate cardiovascular disease in children and adolescents.

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Pediatric reference value distributions and covariate-stratified reference intervals for 29 endocrine and special chemistry biomarkers on the Beckman Coulter Immunoassay Systems: a CALIPER study of healthy community children

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2015-0558 ◽

2016 ◽

Vol 54 (4) ◽

Cited By ~ 9

Author(s):

Kimiya Karbasy ◽

Danny C.C. Lin ◽

Alexandra Stoianov ◽

Man Khun Chan ◽

Victoria Bevilacqua ◽

...

Keyword(s):

Pediatric Population ◽

Reference Value ◽

Reference Interval ◽

Reference Intervals ◽

Healthy Children ◽

Serum Samples ◽

Laboratory Assessment ◽

Research Initiative ◽

Closing The Gaps ◽

Gender Based

AbstractThe CALIPER program is a national research initiative aimed at closing the gaps in pediatric reference intervals. CALIPER previously reported reference intervals for endocrine and special chemistry markers on Abbott immunoassays. We now report new pediatric reference intervals for immunoassays on the Beckman Coulter Immunoassay Systems and assess platform-specific differences in reference values.A total of 711 healthy children and adolescents from birth to <19 years of age were recruited from the community. Serum samples were collected for measurement of 29 biomarkers on the Beckman Coulter Immunoassay Systems. Statistically relevant age and/or gender-based partitions were determined, outliers removed, and reference intervals calculated in accordance with Clinical and Laboratory Standards Institute (CLSI) EP28-A3c guidelines.Complex profiles were observed for all 29 analytes, necessitating unique age and/or sex-specific partitions. Overall, changes in analyte concentrations observed over the course of development were similar to trends previously reported, and are consistent with biochemical and physiological changes that occur during childhood. Marked differences were observed for some assays including progesterone, luteinizing hormone and follicle-stimulating hormone where reference intervals were higher than those reported on Abbott immunoassays and parathyroid hormone where intervals were lower.This study highlights the importance of determining reference intervals specific for each analytical platform. The CALIPER Pediatric Reference Interval database will enable accurate diagnosis and laboratory assessment of children monitored by Beckman Coulter Immunoassay Systems in health care institutions worldwide. These reference intervals must however be validated by individual labs for the local pediatric population as recommended by CLSI.

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Pediatric reference interval verification for endocrine and fertility hormone assays on the Abbott Alinity system

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2021-0337 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Mary Kathryn Bohn ◽

Siobhan Wilson ◽

Alexandra Hall ◽

Khosrow Adeli

Keyword(s):

Clinical Decision Making ◽

De Novo ◽

Reference Interval ◽

Clinical Decision ◽

Reference Intervals ◽

Healthy Children ◽

Confidence Limits ◽

Test Results ◽

Serum Samples ◽

Abbott Architect

Abstract Objectives The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has developed an extensive database of reference intervals (RIs) for several biomarkers on various analytical systems. In this study, pediatric RIs were verified for key immunoassays on the Abbott Alinity system based on the analysis of healthy children samples and comparison to comprehensive RIs previously established for Abbott ARCHITECT assays. Methods Analytical performance of Alinity immunoassays was first assessed. Subsequently, 100 serum samples from healthy children recruited with informed consent were analyzed for 16 Alinity immunoassays. The percentage of test results falling within published CALIPER ARCHITECT reference and confidence limits was determined. If ≥ 90% of test results fell within the confidence limits, they were considered verified based on CLSI guidelines. If <90% of test results fell within the confidence limits, additional samples were analyzed and new Alinity RIs were established. Results Of the 16 immunoassays assessed, 13 met the criteria for verification with test results from ≥ 90% of healthy serum samples falling within the published ARCHITECT confidence limits. New CALIPER RIs were established for free thyroxine and prolactin on the Alinity system. Estradiol required special considerations in early life. Conclusions Our data demonstrate excellent concordance between ARCHITECT and Alinity immunoassays, as well as the robustness of previously established CALIPER RIs for most immunoassays, eliminating the need for de novo RI studies for most parameters. Availability of pediatric RIs for immunoassays on the Alinity system will assist clinical laboratories using this new platform and contribute to improved clinical decision-making.

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Pediatric reference intervals for 1,25-dihydroxyvitamin D using the DiaSorin LIAISON XL assay in the healthy CALIPER cohort

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2017-0767 ◽

2018 ◽

Vol 56 (6) ◽

pp. 964-972 ◽

Cited By ~ 7

Author(s):

Victoria Higgins ◽

Dorothy Truong ◽

Nicole M.A. White-Al Habeeb ◽

Angela W.S. Fung ◽

Barry Hoffman ◽

...

Keyword(s):

Children And Adolescents ◽

Critical Role ◽

Reference Interval ◽

Reference Intervals ◽

Biologically Active ◽

Specific Reference ◽

Healthy Children ◽

Serum Samples ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D

Abstract Background: 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active vitamin D metabolite, plays a critical role in calcium and phosphate homeostasis. 1,25(OH)2D is measured to assess calcium and phosphate metabolism, particularly during periods of profound growth and development. Despite its importance, no reliable pediatric reference interval exists, with those available developed using adult populations or out-dated methodologies. Using the fully automated chemiluminescence immunoassay by DiaSorin, we established 1,25(OH)2D pediatric reference intervals using healthy children and adolescents from the CALIPER cohort. Methods: Serum samples from healthy subjects (0 to <19 years) were analyzed for 1,25(OH)2D using the DiaSorin LIAISON XL assay and age-specific reference intervals were established. The Mann-Whitney U-test was used to determine seasonal differences. Pooled neonatal and infantile samples were quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine if elevated concentrations during the first year of life may be attributed to cross-reacting moieties. Results: Three reference interval age partitions were required with highest levels in subjects 0 to <1 year (77–471 pmol/L), which declined and narrowed after 1 year (113–363 pmol/L) and plateaued at 3 years (108–246 pmol/L). 1,25(OH)2D concentration was not significantly affected by seasonal variation or sex. Elevated 1,25(OH)2D concentrations in neonatal and infantile samples may be the result of an interfering substance. The absence of 3-epi-1,25-dihydroxyvitamin D in the pooled samples makes it unlikely to be the interfering moiety. Conclusions: Pediatric reference intervals for 1,25(OH)2D were established to improve test result interpretation in children and adolescents. 1,25(OH)2D is elevated in a proportion of neonates and infants, which may be the result of a cross-reacting moiety.

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Sources of variation and establishment of Russian reference intervals for major hormones and tumor markers

10.1101/2020.05.26.116269 ◽

2020 ◽

Author(s):

Anna Ruzhanskaya ◽

Kiyoshi Ichihara ◽

Svetlana Evgina ◽

Irina Skibo ◽

Nina Vybornova ◽

...

Keyword(s):

Tumor Markers ◽

Sex Hormones ◽

Parametric Method ◽

Bimodal Distribution ◽

Reference Intervals ◽

Careful Consideration ◽

Russian Population ◽

Serum Samples ◽

Female Sex Hormones ◽

Sources Of Variation

AbstractObjectivesA multicenter study was organized to explore sources of variation (SVs) of reference values (RVs) for 24 major immunochemistry analytes and to determine reference intervals (RIs) for the Russian population.MethodsAccording to IFCC Committee on Reference Intervals and Decision Limits (C-RIDL) protocol, 793 healthy volunteers were recruited in St. Petersburg, Moscow, and Yekaterinburg. Serum samples were tested for five tumor markers, 19 hormones and related tests by Beckman Coulter’s UniCel DxI 800 immunochemistry analyzer. SVs were explored using multiple regression analysis and ANOVA. Standard deviation ratio (SDR) of 0.4 was used as primary guide for partitioning RIs by gender and age.ResultsSDR for between-city difference was <0.4 for all analytes. Secondary exclusion of individuals was done under the following conditions: for female sex-hormones, those with contraceptives (8%); for CA19-9, those supposed to have negative Lewis blood-group (10.5%); for insulin, those with BMI≥28 kg/m2 (29.9%); for the thyroid panel, those with anti-thyroid antibodies (10.3% in males; 24.5% in females). Gender-specific RIs were required for all analytes except CA19-9, CA15-3, thyroid-related tests, parathyroid hormone, and insulin. Age-specific RIs were required for α-fetoprotein and all sex-hormones except testosterone. RIs were generally derived by parametric method after Gaussian transformation using modified Box-Cox formula. Exceptions were growth hormone, estradiol, and progesterone, for which nonparametric method was required due to bimodal distribution and/or insufficient detection limit.ConclusionRIs for major hormones and tumor markers specific for the Russian population were derived based on the up-to-date internationally harmonized protocol by careful consideration of analyte-specific SVs.

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Influence of ethnicity on biochemical markers of health and disease in the CALIPER cohort of healthy children and adolescents

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2019-0876 ◽

2020 ◽

Vol 58 (4) ◽

pp. 605-617 ◽

Cited By ~ 2

Author(s):

Houman Tahmasebi ◽

Shervin Asgari ◽

Alexandra Hall ◽

Victoria Higgins ◽

Ashfia Chowdhury ◽

...

Keyword(s):

Children And Adolescents ◽

Clinical Decision Making ◽

Pediatric Population ◽

Statistical Significance ◽

Immunoglobulin A ◽

Clinical Decision ◽

Reference Intervals ◽

Immunoglobulin M ◽

Healthy Children ◽

Pediatric Study

AbstractBackgroundAccurate pediatric reference intervals (RIs) for laboratory tests determined in a healthy pediatric population are essential for correct laboratory test interpretation and clinical decision-making. In pediatrics, RIs require partitioning by age and/or sex; however, the need for partitioning based on ethnicity is unclear. Here, we assessed the influence of ethnicity on biomarker concentrations in the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort of healthy children and adolescents and compared the results with the National Health and Nutrition Examination Survey (NHANES).MethodsA total of 52 biomarkers were measured in a multiethnic population of 846–1179 healthy children (aged 5 to <19 years) upon informed consent. Biomarker concentrations were retrospectively compared between four major ethnic groups (i.e. Black, Caucasian, East Asian, and South Asian, determined by parental ethnicity). Retrospective results were verified prospectively using an additional 500 healthy pediatric samples with equal sample size across ethnicities. Ethnic-specific differences were assessed based on statistical significance and biological and analytical variations. Appropriate age-, sex-, and ethnic-specific RIs were calculated.ResultsEthnic-specific differences were not observed for 34 biomarkers examined in the retrospective analysis, while 18 demonstrated statistically significant ethnic differences. Among these, seven analytes demonstrated ethnic-specific differences in the prospective analysis: vitamin D, amylase, ferritin, follicle-stimulating hormone (FSH), immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM). Analysis of select NHANES data confirmed CALIPER findings.ConclusionsThis is the first comprehensive Canadian pediatric study examining ethnic-specific differences in common biomarkers. While the majority of biomarkers did not require ethnic partitioning, ethnic-specific RIs were established for seven biomarkers showing marked differences. Further studies in other populations are needed to confirm our findings.

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Complex Biological Pattern of Fertility Hormones in Children and Adolescents: A Study of Healthy Children from the CALIPER Cohort and Establishment of Pediatric Reference Intervals

Clinical Chemistry ◽

10.1373/clinchem.2013.204123 ◽

2013 ◽

Vol 59 (8) ◽

pp. 1215-1227 ◽

Cited By ~ 50

Author(s):

Danijela Konforte ◽

Jennifer L Shea ◽

Lianna Kyriakopoulou ◽

David Colantonio ◽

Ashley H Cohen ◽

...

Keyword(s):

Children And Adolescents ◽

Clinical Laboratory ◽

Pediatric Population ◽

Pubertal Development ◽

Tanner Stage ◽

Reference Intervals ◽

Sex Hormone Binding Globulin ◽

Specific Reference ◽

Healthy Children ◽

Pubertal Stage

BACKGROUND Pediatric endocrinopathies are commonly diagnosed and monitored by measuring hormones of the hypothalamic-pituitary-gonadal axis. Because growth and development can markedly influence normal circulating concentrations of fertility hormones, accurate reference intervals established on the basis of a healthy, nonhospitalized pediatric population and that reflect age-, gender-, and pubertal stage–specific changes are essential for test result interpretation. METHODS Healthy children and adolescents (n = 1234) were recruited from a multiethnic population as part of the CALIPER study. After written informed parental consent was obtained, participants filled out a questionnaire including demographic and pubertal development information (assessed by self-reported Tanner stage) and provided a blood sample. We measured 7 fertility hormones including estradiol, testosterone (second generation), progesterone, sex hormone–binding globulin, prolactin, follicle-stimulating hormone, and luteinizing hormone by use of the Abbott Architect i2000 analyzer. We then used these data to calculate age-, gender-, and Tanner stage–specific reference intervals according to Clinical Laboratory Standards Institute C28-A3 guidelines. RESULTS We observed a complex pattern of change in each analyte concentration from the neonatal period to adolescence. Consequently, many age and sex partitions were required to cover the changes in most fertility hormones over this period. An exception to this was prolactin, for which no sex partition and only 3 age partitions were necessary. CONCLUSIONS This comprehensive database of pediatric reference intervals for fertility hormones will be of global benefit and should lead to improved diagnosis of pediatric endocrinopathies. The new database will need to be validated in local populations and for other immunoassay platforms as recommended by the Clinical Laboratory Standards Institute.

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Paediatric reference intervals for 17 Roche cobas 8000 e602 immunoassays in the CALIPER cohort of healthy children and adolescents

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2019-0707 ◽

2019 ◽

Vol 57 (12) ◽

pp. 1968-1979 ◽

Cited By ~ 2

Author(s):

Mary Kathryn Bohn ◽

Victoria Higgins ◽

Shervin Asgari ◽

Felix Leung ◽

Barry Hoffman ◽

...

Keyword(s):

Children And Adolescents ◽

Reference Values ◽

Laboratory Tests ◽

Clinical Decision Making ◽

Reference Intervals ◽

Healthy Children ◽

Serum Samples ◽

Clinical Laboratories ◽

Age And Sex ◽

Roche Cobas

Abstract Background The diagnostic utility of laboratory tests in paediatric medicine relies heavily on the availability of appropriate reference intervals (RIs). The Canadian Laboratory Initiative on Paediatric Reference Intervals (CALIPER) has established a comprehensive database of covariate-stratified RIs for many paediatric laboratory tests using a large, healthy reference population. Several automated analysers in widespread use in clinical laboratories have already been studied. Here, we extend the testing to Roche immunoassays and report, for the first time, comprehensive paediatric RIs for 17 endocrine and special chemistry markers. Methods A total of 741 healthy children and adolescents (1 day to <19 years) were recruited and serum samples were analysed for 17 immunoassays on the Roche cobas 8000 e602 Immunoassay Analyzer. Age and sex-specific RIs were established and corresponding 90% confidence intervals (CIs) were calculated in accordance with Clinical and Laboratory Standards Institute guidelines. Results Reference values for all analytes measured required age partitioning, particularly during early life and throughout adolescence. Of the 17 analytes measured, eight required sex partitioning, including ferritin, thyroid stimulating hormone (TSH), total triiodothyronine (TT3) and all fertility/sex hormones, except prolactin. Conclusions This is the first study to determine accurate paediatric RIs for Roche immunoassays. RIs were generally similar to those previously published by CALIPER on other analytical platforms, highlighting the reproducibility of age- and sex-specific trends in reference values observed across the paediatric age range. The RIs established in this study will improve the accuracy of test result interpretation and clinical decision-making in clinical laboratories utilising Roche immunoassays.

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