Age- and sex-specific pediatric reference intervals: study design and methods illustrated by measurement of serum proteins with the Behring LN Nephelometer.

1988 ◽  
Vol 34 (8) ◽  
pp. 1618-1621 ◽  
Author(s):  
G Lockitch ◽  
A C Halstead ◽  
G Quigley ◽  
C MacCallum

Abstract We analyzed blood from 450 healthy children and adolescents, ages one to 19 y, as well as term and preterm infants, to define age- and sex-specific reference intervals for numerous blood constituents. Reference intervals were derived by using nonparametric methods to determine the 0.025 and 0.975 fractiles. Ten serum proteins were measured with the Behring LN Nephelometer. Girls over 10 years of age had higher concentrations of ceruloplasmin and alpha 1-antitrypsin than other children had. There was no sex-related difference in reference intervals for the other proteins tested. Reference intervals are presented for immunoglobulins G, A, and M, complement fractions C3c and C4, ceruloplasmin, transferrin, alpha 1-antitrypsin, retinol-binding protein, and prealbumin (transthyretin).

2019 ◽  
Vol 47 (7) ◽  
pp. 3151-3159 ◽  
Author(s):  
Changjin Liu ◽  
Jing Wen ◽  
Jialin Xiang ◽  
Xuhong Ouyang ◽  
Yan Yang ◽  
...  

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.


2020 ◽  
Vol 154 (3) ◽  
pp. 342-352 ◽  
Author(s):  
Victoria Higgins ◽  
Houman Tahmasebi ◽  
Mary Kathryn Bohn ◽  
Alexandra Hall ◽  
Khosrow Adeli

Abstract Objectives The objective of this study was to establish comprehensive age- and sex-specific reference intervals for hematologic parameters in the CALIPER cohort of healthy children and adolescents. Methods A total of 536 healthy children and adolescents (birth to 21 years) were recruited with informed consent, and whole blood samples were analyzed for 27 hematologic parameters on the Beckman Coulter DxH 520 system. Age- and sex-specific pediatric reference standards were established. Reference values obtained on the DxH 520 were also compared with data obtained on a larger laboratory-based instrument (DxH 900). Results Most hematologic parameters showed significant age- and/or sex-specific changes during growth and development. Of the 27 hematologic parameters, all except four (mean corpuscular hemoglobin concentration, basophil percentage, low hemoglobin density, immature cell percentage) required age partitioning, and eight required sex partitioning. Conclusions This study establishes a robust pediatric hematology reference database that will assist in more accurate test result interpretation. Our data clearly demonstrate significant variation in hematologic parameter concentrations in children and adolescents, necessitating the use of pediatric-specific reference standards.


1988 ◽  
Vol 34 (8) ◽  
pp. 1625-1628 ◽  
Author(s):  
G Lockitch ◽  
A C Halstead ◽  
L Wadsworth ◽  
G Quigley ◽  
L Reston ◽  
...  

Abstract Age- and sex-specific reference intervals based on the 0.025 and 0.975 fractiles of data derived from a healthy pediatric population are presented for zinc, copper, selenium, iron, ferritin, retinol, alpha-tocopherol, and related analytes in serum. Age was an important covariate for copper, selenium, retinol, and tocopherol, and ferritin in boys. Strong correlations were found between retinol and retinol-binding protein, prealbumin (transthyretin), alpha-tocopherol, and selenium. Tocopherol was highly correlated with both cholesterol and triglycerides. We found no relationship between serum zinc and either retinol or retinol-binding protein. Despite exclusion of children in whom anemia, microcytosis, or variant hemoglobins were found, the 0.025 fractile for iron in several age groups was even less than the concentration considered to indicate poor iron nutritional status.


1992 ◽  
Vol 38 (3) ◽  
pp. 394-399 ◽  
Author(s):  
D J Malvy ◽  
J D Povéda ◽  
M Debruyne ◽  
B Montagnon ◽  
B Burtschy ◽  
...  

Abstract Eight serum proteins were analyzed with the Behring nephelometer in samples from 479 healthy French children, ages three to 16 years. Girls had higher concentrations of IgM and albumin than boys had. Age appeared to be a main factor of variation for the proteins tested. Reference intervals are presented for IgG, IgA, IgM, albumin, transthyretin (prealbumin), retinol-binding protein, alpha 1-acid glycoprotein, and C-reactive protein. The significance of increased concentrations of C-reactive protein within a community is discussed.


Author(s):  
Mary Kathryn Bohn ◽  
Paul Horn ◽  
Donna League ◽  
Paul Steele ◽  
Alexandra Hall ◽  
...  

Abstract Objectives Rapid development in childhood and adolescence combined with lack of immunoassay standardization necessitates the establishment of age-, sex-, and assay-specific reference intervals for immunochemical markers. This study established reference intervals for 11 immunoassays on the new Siemens Healthineers Atellica® IM Analyzer in the healthy CALIPER cohort. Methods A total of 600 healthy participants (birth to 18 years) were recruited from the community, and serum samples were collected with informed consent. After sample analysis, age- and sex-specific differences were assessed, and outliers were removed. Reference intervals were established using the robust method (40–<120 participants) or nonparametric method (≥120 participants). Results Of the 11 immunoassays studied, nine required age partitioning (i.e., dehydroepiandrosterone-sulfate, estradiol, ferritin, folate, follicle-stimulating hormone, luteinizing hormone, progesterone, testosterone, vitamin B12), and seven required sex partitioning. Free thyroxine and thyroid-stimulating hormone demonstrated no significant age- and/or sex-specific differences. Conclusions Overall, the age- and sex-specific trends observed closely mirrored those previously reported by CALIPER on other platforms as well as other internationally recognized studies. However, established lower and upper limits demonstrated some discrepancies between published values from healthy cohorts on alternate analytical systems, highlighting differences between manufacturers and the need for platform-specific reference intervals for informed pediatric clinical decision-making.


2018 ◽  
Vol 56 (6) ◽  
pp. 964-972 ◽  
Author(s):  
Victoria Higgins ◽  
Dorothy Truong ◽  
Nicole M.A. White-Al Habeeb ◽  
Angela W.S. Fung ◽  
Barry Hoffman ◽  
...  

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.


1988 ◽  
Vol 34 (8) ◽  
pp. 1622-1625 ◽  
Author(s):  
G Lockitch ◽  
A C Halstead ◽  
S Albersheim ◽  
C MacCallum ◽  
G Quigley

Abstract Using the Ektachem-700 multilayer film analyzer, we defined age- and sex-specific reference intervals for 20 analytes in sera from a healthy population of neonates and children ages one to 19 years. Upper and lower normal reference intervals for each analyte were determined by nonparametric methods as the 0.975 and 0.025 fractiles, respectively. Newborns have lower concentrations of total protein and albumin, and higher concentrations of phosphate, bilirubin, and enzymes in serum than older children do. Concentrations of urea, glucose, calcium, phosphate, and bilirubin change rapidly postnatally. Outside the neonatal period, no significant age- or sex-related difference was found for plasma glucose, serum amylase, conjugated or unconjugated bilirubin, or lipase. There was no sex-related difference in reference intervals for albumin, total protein, calcium, phosphate, or urea. However, concentrations of uric acid and creatine kinase are much higher in postpubertal boys than in girls. Alkaline phosphatase values peak later in boys. Except for lactate dehydrogenase and gamma-glutamyltransferase, the reference intervals defined here do not differ strikingly from data derived with use of other analyzers. The age- and sex-related trends are independent of method. However, each laboratory should determine the degree to which these reference ranges can be directly applied to analyses performed with another analyzer.


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