Age-specific Reference Intervals Research Articles

Elective ovariohysterectomy or castration can proceed in shelter dogs despite mild to moderate presurgical leukocytosis.

To determine whether shelter dogs presenting for elective ovariohysterectomy or castration have leukocytosis, whether leukocytes are associated with age and infection, and whether leukocytosis precludes progression to surgery. 138 dogs (from 13 regional shelters) presented for ovariohysterectomy or castration between October 7 and December 6, 2019. For this prospective study, each dog underwent presurgical physical examination, CBC, and tests for Dirofilaria immitis antigen and Anaplasma phagocytophilum, Borrelia burgdorferi, and Ehrlichia canis antibodies, with additional tests performed as needed. Dogs were aged by dentition as juvenile (< 3 or ≥ 3 to ≤ 6 months) or adult (> 6 months). Leukogram results were compared across age groups with recognized infections and parasitism and with dogs' progression to surgery. There were 34 dogs < 3 months old, 22 dogs ≥ 3 to ≤ 6 months old, and 82 > 6 months old. Sixty-three of 138 (45.6%) dogs had leukocytosis (median, 16,500 cells/µL; range, 13,700 to 28,300 cells/µL). Dogs < 3 months of age had higher median leukocyte and lymphocyte counts (14,550 cells/µL and 3,700 cells/µL, respectively) than dogs > 6 months of age (12,500 cells/µL and 2,400 cells/µL, respectively). Only 1 dog had a stress leukogram. Forty-seven dogs had recognized infection, but there was no association with leukocytosis. Surgery proceeded successfully for all dogs with leukocytosis. Mild to moderate leukocytosis is common before elective surgery in shelter dogs, but surgery can proceed safely. A CBC should be reserved for ill-appearing dogs rather than as a screening test, and age-specific reference intervals should be considered.

Establishment of reference intervals of homocysteine, cysteine, and methionine in apparently healthy Chinese adults

Background It has been widely reported that the key biomarkers of homocysteine metabolic pathways have emerged as markers or independent risk factors for cardiovascular disease and many other diseases. To improve the accuracy of evaluation in China, we establish the reference intervals of serum homocysteine (Hcy), cysteine (Cys), and methionine (Met) in apparently healthy Chinese adults. Methods We examined 1553 subjects aged ≥20 years who underwent Hcy metabolic pathway tests, in the Chaoyang Central Hospital between January 2019 and December 2020. The serum Hcy, Cys, and Met levels were simultaneously determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Multiple regression analysis was performed to identify sources of variation. A nonparametric method was used to establish the reference intervals. Results Gender differences were observed in Hcy and Met, with higher levels in males. Reference intervals for males were 6.09–17.00 μmol/L (Hcy) and 19.31–33.68 μmol/L (Met); conversely, the reference intervals for females were 4.61–14.61 μmol/L (Hcy) and 16.16–30.35 μmol/L (Met). The serum Cys reference intervals were seen to be gender-independent, but age-dependent reference intervals were needed; those for Cys were 188.85–334.27 μmol/L, 200.48–340.66 μmol/L, and 216.03–349.67 μmol/L in <40, 40–50, and ≥50 years, respectively. Conclusions By this study, the gender- or age-specific reference intervals of Hcy, Cys, and Met that were matched with the Chinese population were established, providing valuable references for clinical work and laboratory researches.

Pediatric ionized calcium reference intervals from archived radiometer data

BackgroundMeasurement of ionized calcium (iCa) reflects bioavailable calcium and has significant utility in children. However, robust pediatric iCa reference intervals (RI) have not been well-established. In this study, we retrospectively calculated RI for iCa in a pediatric population by accessing archived data acquired on Radiometer instruments and applying stringent exclusion criteria. MethodsData saved on 4 Radiometer ABL800 FLEX blood gas analyzers were queried. Exclusion criteria were applied based on information available from these instruments. iCa results were plotted and inflection points were visually identified. Following outlier removal and partition verification, age-specific RI were calculated using a nonparametric rank order approach from > 5,000 individuals. Finally, the stringency of the exclusion criteria was assessed by calculating RI from additional results in the dataset and comparing to existing in-house ranges. ResultsSix age-specific iCa partitions were established from 0 to 19 years. Relative to adults, wider ranges for the central 95th percentile were observed early in life that progressively narrowed with increasing age and approached adult concentrations by 2.5 years. Analysis of concurrent data for sodium and creatinine in the dataset suggest the applied exclusion criteria reduced the likelihood of including results from acutely-ill children. ConclusionsNormal concentrations of iCa in children are more variable than adults. Observed differences may reflect the transition from maternally supplied calcium to nutritional sources, the maturation of calcium homeostatic mechanisms, and/or the need for calcium for growth/development. This study also demonstrates the feasibility and advantages of using data archived on Radiometer analyzers to establish pediatric RI. This approach enables rapid, cost-effective evaluation of large datasets and may be a feasible option when prospective or detailed retrospective analyses are not possible.

Establishment of Age-Specific Whole Blood Biochemistry and Gas Reference Intervals in Broiler Chickens using the i-STAT and the Vetscan VS2 Portable Analyzers.

Whole blood biochemistry and blood gas analysis are uncommonly used in poultry, but their use could improve the diagnosis of certain diseases or aid in monitoring flock health. To create preliminary reference intervals for selected blood analytes in broilers using the i-STAT and Vetscan VS2 (VS2) portable analyzers, we tested broilers at 7, 21, and 35 days of age. A total of 134 venous blood samples from healthy chickens of two different flocks were analyzed. There were significant age-related increases in concentration for glucose, hematocrit, ionized calcium, sodium, and carbon dioxide partial pressure on the i-STAT and for aspartate aminotransferase, creatine kinase, total calcium, phosphorus, and total protein on the VS2. Conversely, significant decreases in concentration were observed for pH, oxygen partial pressure, oxygen saturation on the i-STAT and for uric acid and albumin on the VS2. Additionally, significant differences were found on some blood parameters among the two flocks. Extremely high CK values were found on broilers after 21 days of age, indicating a possible degree of muscle injury during the grow-out. Preliminary reference intervals for all the analytes at each of the age groups were obtained. This study's data provide a starting point for the interpretation of blood analysis in broiler chickens at different ages and offer a new approach to investigate certain metabolic diseases that affect commercial poultry.

Improving diagnostic accuracy in pregnancy with individualised, gestational age-specific reference intervals

Background and aimsInvestigations in pregnancy should be interpreted using pregnancy-specific reference intervals (RIs). However, because of the progressive nature of pregnancy, even pregnancy-specific RIs may not be equally representative at different gestations. We proposed that gestational age-specific RIs may increase diagnostic accuracy over those with fixed limits. Materials and methodsThe trajectory of platelets was mapped in 32,778 pregnant women, using 116,798 results. Then we evaluated the accuracy with which a low measurement in early pregnancy (<3rd centile) predicted thrombocytopaenia at term, compared to the existing limit (<150 × 109/L). ResultsPlatelets fell by 14.8% between 8 and 40 weeks. Platelets below the 3rd centile before 20 weeks predicted thrombocytopaenia at term (<100 × 109/L) with a significantly greater degree of accuracy than a fixed limit (AUC 0.86 vs. 0.76, p = 0.004). ConclusionPregnancy-specific RIs can be defined using routinely collected hospital data, and the abundance of such freely available data enables a detailed investigation of temporal changes throughout gestation. Individualised RIs offer improved accuracy profiles, over and above those already derived specifically from pregnant populations. Clinicians should consider how this may be used to improve diagnostic accuracy for biomarkers used in current clinical practice, and those yet to be defined.

Complex biological patterns of soluble cytokines and CD163 in childhood necessitating age-specific reference intervals for evidence-based clinical interpretation

BackgroundCytokine measurements to support clinical laboratory and research investigations have become increasingly common in pediatrics. However, there is a paucity of accurate pediatric reference intervals (RIs) essential to the interpretation of cytokine results. To address this gap, here, we establish age- and sex-specific pediatric reference values for clinically relevant inflammatory markers including CD163, and the cytokines IL-1β, IL-6, IL-10, IL-18, TNF-α, IFN-γ, and CXCL-9. MethodsHealthy children and adolescents (n = 311, 1–19 years) were recruited as part of the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) study. Multi-analyte measurements in plasma and analytical performance verification were conducted on the ProteinSimple® Ella™ automated immunoassay platform (Bio-Techne, MN, USA). Age- and sex-specific RIs were calculated based on Clinical and Laboratory Standards Institute guidelines. Additionally, 75th and 95th percentile cut-offs were determined. ResultsThree types of reference value distributions were observed: (a) consistent levels throughout age and sex: IL-6, and IFN-γ, (b) gradual decline in concentration with age: CD163, TNF-α, CXCL-9, and IL-10, (c) significantly higher concentrations during ages 4–14 years than earlier and later ages: IL-1β and IL-18. Reference values for CXCL-9, IL-10, and TNF-α under 8 years of age differed significantly from older children. CD163, IL-18 and IL-1β required three age partitions. CD163 demonstrated significant sex differences in ages 8–13 years. ConclusionThe circulating profile of cytokines in children is complex and can vary by age and sex. This necessitates careful interpretation of test results based on age and/or sex specific RIs facilitating more accurate clinical decision making.

Serum and Urinary Osteocalcin in Healthy 7- to 19-Year-Old Finnish Children and Adolescents.

Children and adolescents have high bone turnover marker (BTM) levels due to high growth velocity and rapid bone turnover. Pediatric normative values for BTMs reflecting bone formation and resorption are vital for timely assessment of healthy bone turnover, investigating skeletal diseases, or monitoring treatment outcomes. Optimally, clinically feasible measurement protocols for BTMs would be validated and measurable in both urine and serum. We aimed to (a) establish sex- and age-specific reference intervals for urinary and serum total and carboxylated osteocalcin (OC) in 7- to 19-year-old healthy Finnish children and adolescents (n = 172), (b) validate these against standardized serum and urinary BTMs, and (c) assess the impact of anthropometry, pubertal status, and body composition on the OC values. All OC values in addition to other BTMs increased with puberty and correlated with pubertal growth, which occurred and declined earlier in girls than in boys. The mean serum total and carboxylated OC and urinary OC values and percentiles for sex-specific age categories and pubertal stages were established. Correlation between serum and urinary OC was weak, especially in younger boys, but improved with increasing age. The independent determinants for OC varied, the urinary OC being the most robust while age, height, weight, and plasma parathyroid hormone (PTH) influenced serum total and carboxylated OC values. Body composition parameters had no influence on any of the OC values. In children and adolescents, circulating and urinary OC reflect more accurately growth status than bone mineral density (BMD) or body composition. Thus, validity of OC, similar to other BTMs, as a single marker of bone turnover, remains limited. Yet, serum and urinary OC similarly to other BTMs provide a valuable supplementary tool when assessing longitudinal changes in bone health with repeat measurements, in combination with other clinically relevant parameters.

Effect of age, sex, and body size on the blood biochemistry and physiological constants of dogs from 4 wk. to >\u200952 wk. of age

BackgroundBlood biochemistry and reference intervals help to differentiate between healthy and ill dogs as well as to provide information for the prognosis, evaluation, and monitoring; however, these intervals are often obtained from adult animals. It is essential to understand that puppies and adults are physiologically different, which justifies the need to obtain age-specific biochemical reference intervals. The aim of this research was to assess the potential effect of age, sex, body size, and their interaction on routine biochemical analytes and physiological constants (body temperature, heart rate, and respiratory rate). To carry out the research, we selected 197 healthy dogs of both sexes and different body sizes (small, medium and large) classified by age: group I (4–8 wk), group II (9–24 wk), group III (25–52 wk), and group IV (> 52 wk). The biochemical analysis included the measurement of the enzymatic activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and the concentrations of cholesterol, triglycerides, total proteins, albumin, globulins, glucose, urea, and creatinine. Statistical analyses used analysis of variance (ANOVA) and a general linear model (GLM), which allows the comparison of multiple factors at two or more levels (p < 0.05).ResultsThe results of this study showed that ALT, total protein, albumin, globulin, urea, creatinine, and body temperature levels were lower in puppies than in adult dogs of group IV (p < 0.05), while the enzymatic activity of ALP, LDH, glucose concentration, and heart rate were higher. Whereas sex, body size and the interaction did not show a significant effect (p > 0.05).ConclusionsSome biochemical components are influenced by age. For this reason, this manuscript contributes with additional data for the clinical interpretation of blood biochemical results in puppies.

Establishing age-stratified red blood cell fatty acid reference ranges using model-based clustering and iterative application of the harris-boyd method

BackgroundThe current assessment of nutritional status and diagnosis of essential fatty acids deficiency (EFAD) utilizes the analysis of long-chain fatty acids (LCFAs) in serum or plasma; however, these concentrations do not represent habitual LCFA intake. LCFAs in red blood cells (RBCs) are less prone to intra-individual variability and exclude the need for fasting, which is unrealistic in pediatric populations. Our study objective was to characterize the RBC LCFA profiles in pediatric and adult reference populations and establish age-specific reference intervals (RIs). MethodsTwenty-one LCFAs in RBCs were measured in 523 pediatric and adult controls by gas chromatography-mass spectrometry. Model-based clustering was used to identify possible age subgroups. After removing outliers by the Tukey method, initial age subgroups were then compared using the Harris-Boyd method in an iterative manner. RIs (95%), with confidence intervals (90%), in the final age groups were established using parametric or non-parametric statistics. ResultsOur data showed heterogeneous changes in the concentrations of most LCFAs and the EFAD biomarkers (mead acid, Triene/Tetraene ratio) during infancy. Model-based clustering identified six initial age subgroups per fatty acid, on average. Our application of the iterative Harris-Boyd method decreased the average number of age groups to three per fatty acid, with 13 total unique age cut-offs. Finally, using these age groups, we established age-specific RIs for 21 fatty acids, six group totals, and the Triene/Tetraene ratio. ConclusionOur study revealed significant age-dependent changes in RBC fatty acid profiles warranting separate pediatric and adults RIs. Model-based clustering and the iterative application of the Harris-Boyd method were successfully used to establish RBC fatty acid RIs for an objective assessment of long-term nutritional status in pediatric and adult populations.

Nomogram of age-specific anti-Müllerian hormone levels in healthy Egyptian females.

BackgroundAnti-Müllerian hormone (AMH) is an important determinant of ovarian reserve in fertility workups in many clinical settings. Thus, we investigated the age dependent decline in AMH specific to the Egyptian population and sought to establish an age dependent reference interval parametrically.MethodsSerum samples were collected from 841 apparently healthy women. AMH was measured using an electro-chemiluminescent technique. Box-Cox power transformation was used to make the AMH distribution Gaussian for parametric derivation of reference intervals.ResultsPower of 0.4 was found optimal for Gaussian transformation of AMH reference values. We demonstrate the strong negative relation between circulating AMH and female age with Spearman’s correlation coefficient of rS = −0.528. Age-specific reference interval was determined for every 5 years of age from 16 to 49, and nomogram was constructed by smoothing the lines connecting adjacent lower and upper reference limits.ConclusionThe age-specific reference intervals and the age-AMH nomogram could be valuable in the clinical practice of in reproductive medicine. To our knowledge, this is the first study to confirm AMH levels in Egyptian females. We were able to explore age-related AMH levels specific to Egyptian females in the fertile age group and to treat skewed AMH data in a multi-step scheme using power transformation. Thus, a more accurate nomogram was constructed accommodating a profile delineated for a wide age range and a rescaled AMH axis improving its usability.

Sex- and age-specific reference intervals for diagnostic ratios reflecting relative activity of steroidogenic enzymes and pathways in adults.

ObjectiveDiagnostic ratios calculated from urinary steroid hormone metabolites are used as a measure for the relative activity of steroidogenic enzymes or pathways in the clinical investigation of steroid metabolism disorders. However, population-based sex- and age-specific reference intervals and day-night differences in adults are lacking.MethodsSixty-five diagnostic ratios were calculated from steroid metabolites measured by GC-MS in day- and night-time and in 24-hour urine from 1128 adults recruited within the Swiss Kidney Project on Genes in Hypertension (SKIPOGH), a population-based, multicenter cohort study. Differences related to sex, age and day- and night-time were evaluated and reference curves in function of age and sex were modelled by multivariable linear mixed regression for diagnostic ratios and were compared to values from the literature.ResultsMost ratios had sex- and age-specific relationships. For each ratio, percentiles were plotted in function of age and sex in order to create reference curves and sex- and age-specific reference intervals derived from 2.5th and 97.5th percentiles were obtained. Most ratios reflected a higher enzyme activity during the day compared to the night.ConclusionsSex- and age-specific references for 24 hours, day and night urine steroid metabolite ratios may help distinguishing between health and disease when investigating human disorders affecting steroid synthesis and metabolism. The day-night differences observed for most of the diagnostic ratios suggest a circadian rhythm for enzymes involved in human steroid hormones metabolism.

Procollagen III, N-terminal propeptide (PIIINP): establishment of reference intervals in Northern European adults and children using the MAGLUMI 800 chemiluminescence immunoassay

Procollagen III, N-terminal propeptide (PIIINP) is used as a biomarker for increased collagen III-synthesis. Reference intervals have not been established for the MAGLUMI 800 chemiluminescence immunoassay (CLIA) in Northern European adults or in children. The present study aimed to establish age-specific reference intervals in a Northern European population. PIIINP serum levels were analysed in healthy blood donors 19–67 years (n = 240) and children 2–18 years (n = 420). Furthermore, we investigated total imprecision and stability at room temperature and at −20 °C and performed a method comparison between MAGLUMI 800 CLIA (Snibe Diagnostics, Shenzhen, China) and ADVIA Centaur CP (Siemens Healthcare Diagnostics, Tarrytown, NY,USA). PIIINP was influenced by age but not sex. We established the following reference intervals: 2–10 years, 18–62 µg/L; 11–18 years, 15–75 µg/L; 19–39 years, 15–55 µg/L; 40–67 years, 14–31 µg/L. Total imprecision for PIIINP on MAGLUMI 800 was acceptable with coefficients of variation of 4.9% in the low range and 9.4% in the high range. PIIINP was stable for 24 h at room temperature after centrifugation and for at least 7 months at −20 °C. MAGLUMI 800 yielded significantly higher PIIINP levels than ADVIA Centaur CP. In conclusion, we established age-specific reference intervals for PIIINP using MAGLUMI 800 CLIA in a large Danish cohort. Our results may be useful for other laboratories wishing to establish PIIINP on the same platform and may provide improved guidance for medical doctors treating both children and adults with fibrotic disorders.

Establishment of Early Pregnancy Related Thyroid Hormone Models and Reference Intervals for Pregnant Women in China Based on Real World Data.

Thyroid hormone reference intervals are crucial for diagnosing and monitoring thyroid dysfunction during early pregnancy, and the dynamic change trend of thyroid hormones during pregnancy can assist clinicians to assess the thyroid function of pregnant women. This study aims to establish early pregnancy related thyroid hormones models and reference intervals for pregnant women. We established two derived databases: derived database* and derived database#. Reference individuals in database* were used to establish gestational age-specific reference intervals for thyroid hormones and early pregnancy related thyroid hormones models for pregnant women. Individuals in database# were apparently healthy non-pregnant women. The thyroid hormones levels of individuals in database# were compared with that of individuals in database* using nonparametric methods and the comparative confidence interval method. The differences in thyroid stimulating hormone and free thyroxine between early pregnant and non-pregnant women were statistically significant (p<0.0001). The reference intervals of thyroid stimulating hormone, free thyroxine and free triiodothyronine for early pregnant women were 0.052-3.393 μIU/ml, 1.01-1.54 ng/dl, and 2.51-3.66 pg/ml, respectively. Results concerning thyroid stimulating hormone and free thyroxine reference intervals of early pregnancy are comparable with those from other studies using the same detection platform. Early pregnancy related thyroid hormones models showed various change patterns with gestational age for thyroid hormones. Early pregnancy related thyroid hormones models and reference intervals for pregnant women were established, so as to provide accurate and reliable reference basis for the diagnosing and monitoring of maternal thyroid disfunction in early pregnancy.

Age-specific reference intervals of serum anti-Müllerian hormone in Chinese girls.

This study aimed to establish anti-Mullerian hormone age-specific reference intervals and determine the correlation between the anti-Mullerian hormone concentration and age, body mass index and concentrations of follicle-stimulating hormones and luteinizing hormone in healthy Chinese girls. Serum anti-Mullerian hormone concentrations of 1702 healthy girls (0-12 years), recruited between March 2018 and December 2019, were determined using the Beckman Access 2 automated chemiluminescence immunoassay. Single-year-specific medians of anti-Mullerian hormone and effects of age, body mass index, follicle-stimulating hormone and luteinizing hormone on anti-Mullerian hormone concentration were analysed. The anti-Mullerian hormone median level continued increasing from birth, reached its peak at age 9 at 4.45 ng/mL (interquartile range [IQR] 2.58-6.90) and then gradually decreased. At age 12, the median reached 1.98 ng/mL (IQR 1.05-3.46). Age-specific reference intervals for anti-Mullerian hormone were established in healthy Chinese girls aged 0-12 years. Anti-Mullerian hormone concentrations showed a moderately positive correlation with age (r = 0.33, P < 0.001). In contrast, follicle-stimulating hormone (r = -0.29, P < 0.001) concentrations were weakly negatively correlated with the serum anti-Mullerian hormone concentration. We established single-year-specific reference intervals for anti-Mullerian hormone in Chinese girls using the Beckman chemiluminescent platform. This reference range can help clinicians accurately understand anti-Mullerian hormone secretion in healthy girls and promote its clinical use.

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

A multicenter study was organized to explore sources of variation (SVs) of reference values (RVs) for 22 major immunochemistry analytes and to determine reference intervals (RIs) for the Russian population. According to IFCC Committee on Reference Intervals and Decision Limits (C-RIDL) protocol, 758 healthy volunteers were recruited in St. Petersburg, Moscow, and Yekaterinburg. Serum samples were tested for five tumor markers, 17 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. SDR 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% males and 11.3% females); for insulin, those with BMI≥28 kg/m2 (31%); for the thyroid panel, those with anti-thyroid antibodies (10.3% males; 24.5% females), for CEA those with smoking habit (30% males and 16% 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 alpha-fetoprotein, CEA, all sex-hormones for females, FSH and progesterone for both sexes. RIs were generally derived by parametric method after Gaussian transformation using modified Box-Cox formula. Exceptions were growth hormone, estradiol for females in postmenopause, and progesterone for females in premenopause, for which nonparametric method was required due to bimodal distribution and/or insufficient detection limit. RIs 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.

Sex and Age-Specific Hematology and Biochemistry Reference Intervals of Live Iberian Hares (Lepus granatensis) and Comparison with Postmortem Sampling.

Hematology and serum biochemistry reference intervals were estimated for the Iberian hare (Lepus granatensis). Most parameters differed significantly between hunted and livetrapped Iberian hares. Significant differences were found for sex (red blood cell count, mean corpuscular volume, total protein, albumin, uric acid, triglycerides, cholesterol, chloride) and age classes (red blood cell count, hematocrit, mean corpuscular hemoglobin, glucose, calcium, and sodium). Sex- and age-specific reference intervals were estimated for these parameters. Red blood cell count, hemoglobin concentration, mean corpuscular hemoglobin, urea, and potassium show seasonal variations, with the lowest values in summer and the highest in winter. Creatinine, calcium, sodium, and phosphorus achieve their highest values in summer and stable baseline values throughout the rest of the year. These reference intervals can be used as baseline to monitor health, physiology, ecology, and nutrition of Iberian hare populations.

Serum TBA and GCA Levels Across Pregnancy and the Gestational Age-Specific Reference Intervals for Pregnant Chinese.

Reference intervals of clinical laboratory indexes are the basis of interpretation of test results. While intrahepatic cholestasis of pregnancy (ICP) could severely threaten maternal and fetal health, reference intervals of the biomarkers serum total bile acids (TBA) and glycocholic acid (GCA) are unsatisfactory. The purpose of this study was to derive gestational age-specific reference intervals for serum TBA and GCA in a Chinese population to promote early diagnosis of ICP. A total of 416 healthy pregnant Chinese were recruited and divided into three groups by gestational age: 140 in the first trimester (1 - 13 weeks) group, 136 in the second trimester (14 - 27 weeks) group, and 140 in the third trimester (≥ 28 weeks) group. Serum TBA and GCA levels were measured respectively by cyclic enzymatic method and latex enhanced immune turbidimetry. Reference intervals were calculated with non-parametric method. The reference intervals of serum TBA are 0.90 - 6.60 μmol/L, 1.20 - 9.10 μmol/L, and 1.50 - 8.90 μmol/L respectively in the first, second, and third trimester. The reference intervals of serum GCA are 0.24 - 1.14 μg/mL in the first and second trimesters (combined) and 0.00 - 2.04 μg/mL in the third trimester. Gestational age-specific reference intervals of serum TBA and GCA for pregnant Chinese were derived in strict accordance with CLSI C28-A3 guidelines, which will be valuable for early diagnosis of ICP.

Percentiles for anthropometric measures in 11–18 years-old students of 73 developing countries

Background and aimsone of the health concerns for any society is to have its own standard of growth. The aim of this study was to provide the age- and sex-specific percentile values of anthropometric measures for adolescents of developing countries. The use of global percentiles in developing countries overestimates underweight and stunting while underestimates overweight and obesity. MethodsThe data were obtained from the Global School-based Student Health Survey (GSHS). This study was conducted on school students, selected by multistage random cluster sampling from 73 developing countries. A parametric method was used for constructing age-specific reference intervals (normal ranges). ResultsIn general, 210,045 11–18 years-old schoolchildren (14.38 ± 1.39) from 73 developing countries between 2003 and 2014 were included in this study, among which 103,080 (49.08%) were male and 106,965 (50.92%) were female. Calculation of body mass index (BMI) percentile showed that for all BMI percentile curves of both sexes, there was a gradual increase up to the age of around 15 years, and then remain stable (except for 95th percentile). Moreover in all weight percentile curves of boys, except 90th and above, there was a slight rise until the age of 18 years. In 10th height percentile curves and above in boys, there was a sharp increase up to the age of 17, followed by a decline. Similarly, this pattern was found for 50th height percentile and above in girls. ConclusionThe use of global percentiles in developing countries overestimates underweight and stunting while underestimates overweight and obesity.

Establishing race-, gender- and age-specific reference intervals for pyridoxal 5′-phosphate in the NHANES population to better identify adult hypophosphatasia

Bisphosphonate treatment in adults with hypophosphatasia (HPP) may increase fracture risk. PLP is a useful marker in biochemically differentiating HPP from osteoporosis in adults. In order to identify elevated PLP, robust reference intervals are needed which are calculated in a large, representative sample population. Complete data from 9069 individuals (ages 20-80, 50.6% female) from two years of the NHANES Survey (2007-2008 and 2009-2010) were investigated. Differences in PLP in the presence of four factors; inflammation (CRP ≥5.0mg/L), low ALP (<36IU/L), chronic kidney disease (eGFR <60mL/min/1.732), and daily vitamin B6 supplementation, were investigated. Race, gender and age differences in PLP were then investigated; 95% reference intervals were calculated that reflected these differences. Inflammation and chronic kidney disease were associated with lower PLP (p<.0001 and p=.0005 respectively), while low ALP and vitamin B6 supplementation were associated with higher PLP (both p<.0001). Individuals were excluded based on the presence of these factors; a reference interval population (n=4463) was established. There were significant differences in PLP depending on race and gender (p<.0001) Increasing age was correlated with decreasing PLP (spearman's rho -0.204, p<.0001). Race- and gender-specific 95% reference intervals were calculated. In male patients, these were also calculated according to age groups: young and older adults (ages 20-49years and ≥50years respectively). In order to identify adult hypophosphatasia based on elevated PLP, considerations must be made depending on the race, gender and age of the individual. Factors associated with significant differences in PLP must also be considered when assessing biochemical measurements.

Establishing Simultaneous T Cell Receptor Excision Circles (TREC) and K-Deleting Recombination Excision Circles (KREC) Quantification Assays and Laboratory Reference Intervals in Healthy Individuals of Different Age Groups in Hong Kong.

The clinical experience gathered throughout the years has raised awareness of primary immunodeficiency diseases (PIDD). T cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) assays for thymic and bone marrow outputs measurement have been widely implemented in newborn screening (NBS) programs for Severe Combined Immunodeficiency. The potential applications of combined TREC and KREC assay in PIDD diagnosis and immune reconstitution monitoring in non-neonatal patients have been suggested. Given that ethnicity, gender, and age can contribute to variations in immunity, defining the reference intervals of TREC and KREC levels in the local population is crucial for setting up cut-offs for PIDD diagnosis. In this retrospective study, 479 healthy Chinese sibling donors (240 males and 239 females; age range: 1 month−74 years) from Hong Kong were tested for TREC and KREC levels using a simultaneous quantitative real-time PCR assay. Age-specific 5th–95th percentile reference intervals of TREC and KREC levels (expressed in copies per μL blood and copies per 106 cells) were established in both pediatric and adult age groups. Significant inverse correlations between age and both TREC and KREC levels were observed in the pediatric age group. A significant higher KREC level was observed in females than males after 9–12 years of age but not for TREC. Low TREC or KREC levels were detected in patients diagnosed with mild or severe PIDD. This assay with the established local reference intervals would allow accurate diagnosis of PIDD, and potentially monitoring immune reconstitution following haematopoietic stem cell transplantation or highly active anti-retroviral therapy in the future.