Gender-specific Reference Intervals Research Articles

Derivation of Russian-specific reference intervals for complete blood count, iron markers and related vitamins.

This study aimed to establish reference intervals (RIs) for Russian adults for hematological parameters including related iron markers and vitamins. Sources of variation of reference values (RVs) and needs for secondary exclusion were explored for proper derivations of RIs. Following the harmonized protocol of the IFCC Committee on Reference Intervals and Decision Limits (C-RIDL), 506 healthy Russians (age 18-80; 46% male) were recruited. Complete blood counts (CBC) and leukocyte differentials, iron markers, vitamin B12, and folate were measured by Beckman Coulter's analyzers. Sources of variation were analyzed by multiple regression analysis, and ANOVAs, and the need for partitioning RVs was decided accordingly. Two schemes of excluding latent anemia were compared: (1) latent abnormal values exclusion method (LAVE) based on associations among CBC parameters, or (2) explicit exclusion of individuals with either ferritin or iron below the respective lower limit of the manufacturer. RIs were determined by the parametric method using two-parameter Box-Cox formula. Gender-specific RIs were required for most analytes, while age-specific RIs were set only for ferritin in females. A BMI-related increase in RVs was prominently observed for reticulocyte parameters, hence we chose to exclude individuals with BMI>28 kg/m2 when establishing the RIs. The LAVE method was more effective in excluding individuals with latent anemia, than exclusion based on low ferritin and/or iron values. International comparison revealed that Russian RIs featured a lower side shift of platelet counts. Similar to African countries, Russian RIs for total leukocyte and neutrophil counts were lower compared to most of other countries. RIs for the Russian population for 34 hematological and related parameters were established using up-to-date methods proposed by C-RIDL. Reducing the influences of latent anemia and obesity on RIs was crucial for erythrocyte parameters. Low levels of Russian RIs observed for platelet and neutrophil counts need further investigation.

Direct, age- and gender-specific reference intervals: applying a modified M-estimator of the Yeo-Johnson transformation to clinical real-world data

Abstract Objectives Reference intervals for the general clinical practice are expected to cover non-pathological values, but also reflect the underlying biological variation present in age- and gender-specific patient populations. Reference intervals can be inferred from routine patient data measured in high capacity using parametric approaches. Stratified reference distributions are obtained which may be transformed to normality via e.g. a Yeo-Johnson transformation. The estimation of the optimal transformation parameter for Yeo-Johnson through maximum likelihood can be highly influenced by the presence of outlying observations, resulting in biased reference interval estimates. Methods To reduce the influence of outlying observations on parametric reference interval estimation, a reweighted M-estimator approach for the Yeo-Johnson (YJ) transformation was utilised to achieve central normality in stratified reference populations for a variety of laboratory test results. The reweighted M-estimator for the YJ transformation offers a robust parametric approach to infer relevant reference intervals. Results The proposed method showcases robustness up to 15 % of outliers present in routine patient data, highlighting the applicability of the reweighted M-estimator in laboratory medicine. Furthermore, reference intervals are personalised based on the patients’ age and gender for a variety of analytes from routine patient data collected in a tertiary hospital, robustly reducing the dimensionality of the data for more data-driven approaches. Conclusions The method shows the advantages for estimating reference intervals directly and parametrically from routine patient data in order to provide expected reference ranges. This approach to locally inferred reference intervals allows a more nuanced comparison of patients’ test results.

Age- and Gender-Specific Reference Intervals for the Fasting Serum Lipid Levels in a Pediatric Population Aged 0-＜15 Years in Nanjing, China.

The lipid reference intervals (RIs) that are currently used for children in China are not based on studies of the local population and normally do not consider age or gender differences. This study aimed to establish age- and sex-specific RIs for the fasting serum lipid levels in the pediatric population aged 0 - 15 years in Nanjing, China. 5,866 children aged 3 days to ＜15 years were recruited to establish serum lipid RIs, and the triglyceride (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) levels were analyzed using the Roche cobas702 automatic biochemical analyzer. Low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (nHDL-C) levels were calculated (LDL-C=TC-HDL-C-TG/5, and nHDL-C=TC-HDL-C). Smoothed percentile curves for the boys and girls were generated using the LMS method. Age- and sex-specific RIs were the determined according to the methods recommended by the Clinical and Laboratory Standards Institute EP28-A3c guidelines. This study showed that the serum lipid levels varied considerably throughout childhood and adolescence, with sex differences, especially in infants aged less than 2 years and puberty. Based on the Harris-Boyd method, sex partitions were required for ages ＜6 months in the TC indicator and for ages ≤ 28 days in LDL-C and nHDL-C. Age partitions were also required for all serum lipid parameters. We established age- and sex-specific RIs for TG, TC, HDL-C, LDL-C, and nHDL-C parameters in children aged 0 days to ＜15 years in Nanjing, China. These data are thus considered to be useful for the screening of dyslipidemia in children and adolescents.

Pediatric reference intervals for serum folate and cobalamin based on a European population without exposure to folic acid fortification

The aim of the present study was to define pediatric reference intervals for serum cobalamin and folate utilizing data generated from a population not exposed to food fortified with folic acid. Folate and cobalamin results analyzed by electrochemiluminescence immunoassay (Roche Cobas) were obtained from 2375 children (2 months to 17.99 years of age). The serum samples were collected between 2011 and 2015 as part of the LIFE (Leipzig Research Centre for Civilization Diseases) Child cohort study in Germany, where folic acid fortification of food is not mandated. These results were used to generate age- and gender-specific reference intervals presented as non-parametric 2.5 and 97.5 percentiles. Because of a subsequent restandardisation of the Roche folate assay in 2016, folate values were recalculated accordingly for adaptation to results obtained using the present calibration. In both genders, folate concentrations decreased continuously with age, whereas cobalamin concentrations peaked at five years of age and then declined. Teenage females had higher concentrations of cobalamin in the age group 12–17.99 years.

Age-, season- and gender-specific reference intervals of serum 25-hydroxyvitamin D3 for healthy children (0 ~ 18 years old) in Nanning area of China

Establishing specific reference intervals (RIs) of serum 25-hydroxyvitamin D3 [25(OH)D] for children is essential for improving the accuracy of diagnosis and prognosis monitoring of diseases such as rickets and growth retardation. The study including 6,627 healthy children was conducted to establish specific RIs of 25(OH)D for children in Nanning area of China. The results showed that there were statistically significant differences among age, season, and gender of serum 25(OH)D levels, and the age-specific RIs of serum 25(OH)D were 20.3 ~ 53.6 ng/mL for 0 ~ ≤ 1 year and 18.9 ~ 49.6 ng/mL for 2 ~ ≤ 3 years. The age-, season-specific RIs of serum 25(OH)D for 4 ~ ≤ 6 years in spring–summer and autumn–winter were 15.8 ~ 42.6 ng/mL and 15.2 ~ 37.7 ng/mL, respectively. The age-, gender-specific RIs of serum 25(OH)D for 7 ~ ≤ 18 years for males and females were 12.1 ~ 36.1 ng/mL and 10.8 ~ 35.3 ng/mL, respectively. This study successfully established the RIs of serum 25(OH)D, which may help to improve disease diagnosis and monitoring for children in the Nanning area of China.

Age-and Gender-Specific Reference Intervals for Systemic Inflammatory Indicators in Healthy Moroccan Adults.

Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and the systemic immune inflammation index (SII) are effective prognostic markers of patients in various clinical situations such as cancer, cardiovascular diseases and inflammatory diseases. This study aims to explore the reference values based on gender and age for NLR, PLR, LMR and SII in the Moroccan population. From January 2018 to February 2020, data of ostensibly healthy adults were collected retrospectively from the laboratory information system (LIS) of the Laboratory for Research and Medical Analysis of the Fraternal Royal Gendarmerie, Rabat (Morocco). A total of 5,898 men and 10,172 women aged between 18 and 90 years were included. RIs of each parameter were established and validated in accordance with the Clinical and Laboratory Standards Institute (CLSI) document C28-A3. NLR was significantly different between men and women (p < 0.05), while PLR, LMR and SII were not. The values of NLR, PLR, LMR and SII differed significantly between different age groups of both genders (p < 0.05). Therefore, RI of PLR, LMR, and SII had to be divided into groups based on age, but not on gender, while establishing the NLR reference intervals took into account both factors; age and gender. This paper provides Reference Intervals for NLR, PLR, LMR, and SII according to age and gender in healthy Moroccan adults. This can improve assessment and potentially widen the use of these biomarkers in Moroccan clinical context.

SCCA and CYFRA 21-1 Reference Intervals for Apparently Healthy Chinese Adults: a Multicenter Cross-Sectional Study.

This study aimed to establish reference intervals for two biomarkers actively utilized in routine annual medical check-ups in China: squamous cell carcinoma antigen (SCCA) and cytokeratin 19 fragment (CYRFA 21-1), and to understand the influence of age, gender, and benign nodule(s) on their levels. This prospective multicenter cross-sectional study continuously enrolled apparently healthy adults attending annual medical check-ups at three sites in 2019. Serum SCCA and CYFRA 21-1 levels were measured using electrochemiluminescence immunoassays. Age- and gender-specific reference intervals for the two biomarkers were established by using the 0 - 95th percentiles with 90% confidence intervals (CIs). The 97.5th percentiles were also provided. A total of 1,017 subjects were enrolled in this study. Both biomarkers were significantly lower in females, and age was negatively associated with SCCA while positively associated with CYFRA 21-1 (all p < 0.0001). No statistically significant differences were determined between subgroups without/with benign nodule(s) despite nodule(s) status (all p > 0.05). The overall reference interval for SCCA is 0 - 2.64 ng/mL and 0 - 4.39 ng/mL for CYFRA 21-1. The age-specific reference intervals for SCCA are 0 - 2.76 ng/mL (18 - 49 years) and 0 - 2.22 ng/mL (≥ 50 years), and for CYFRA 21-1, they are 0 - 3.86 ng/mL (18 - 49 years) and 0 - 4.89 ng/mL (≥ 50 years). The gender-specific reference intervals for SCCA are 0 - 2.83 ng/mL (male) and 0 - 2.49 ng/mL (female), and for CYFRA 21-1, they are 0 - 4.34 ng/mL (male) and 0 - 4.45 ng/mL (female). The reference intervals for SCCA and CYFRA 21-1 established in this study could be utilized in annual medical check-ups and contribute to the screening of lung cancer in China.

Establishment of age- and -gender specific reference intervals for amino acids and acylcarnitines by tandem mass spectrometry in Turkish paediatric population.

We determined age- and gender-specific reference intervals (RIs) for acylcarnitines and amino acids by tandem mass spectrometry (MS/MS) in the Turkish paediatric population by using laboratory information system (LIS) data. A total of 9156 MS/MS results of children between 0-18 years of age, were downloaded from the LIS. Premature infants and newborns followed in the intensive care unit were excluded and only the first result of each patient attending outpatient clinics was included. Children with a known or suspected diagnosis of metabolic disease, malignancy, epilepsy, mental retardation, or genetic disorder were excluded. Laboratory results were evaluated and children with any pathological laboratory finding were excluded, resulting in a final sample size of 3357 (2029 boys and 1328 girls). Blood was collected by capillary puncture and spotted on Whatman 903 filter paper cards and analysed by MS/MS (Shimadzu LCMS-8050, Shimadzu Corporation, Kyoto, Japan). Data were evaluated for age and gender differences and age partitioning was performed according to the literature and visual evaluation of the data. Age subgroups were: ≤ 1 month, 2 months-1 year, 2-5 years, 6-10 years, and 11-18 years. There were significant age-related differences for the majority of amino acids and acylcarnitines thus age dependent RIs were established. Gender-specific RIs were established for tyrosine, leucine-isoleucine, isovalerylcarnitine (C5) and hexadecanoylcarnitine (C16). Establishing age-related RIs can enhance the quality of medical care by facilitating early diagnosis and therapy, especially in certain metabolic disorders presenting with mild biochemical abnormalities and subtle clinical manifestations.

Current practice and recommendations for managing transgender patient data in clinical laboratories in the United Kingdom and Republic of Ireland.

Transgender people may avoid seeking medical care due to previous negative experiences and fear of discrimination. Clinical laboratories can contribute to a poor patient experience and clinical outcome when the design and functionality of laboratory information management systems (LIMS) do not consider the needs of transgender patients. This survey aimed to capture current practices in United Kingdom and Republic of Ireland clinical laboratories concerning how transgender patient data and test requests are managed throughout the total testing process. An anonymous survey was distributed to clinical laboratory professionals in November 2021. Thirty-three questions covered how gender variables are recorded for transgender patients and used to inform gender-specific calculations, test access, and reference intervals (RIs). Of the 66 respondents, 70% were based in laboratories in England, with a majority of laboratories having ISO 15189 accreditation and processing 1000-10,000 blood samples daily. Eighty-five percent stated that their LIMS had a single field recording sex or gender information. Forty-three percent did not limit test access based on gender, but 68% did not append RIs for patients with unknown or indeterminate gender. This survey was the first to quantify how clinical laboratories manage sex and gender information and report results for transgender and non-binary patients, and details several key recommendations based on the survey responses.

Reference Intervals for Plasma Free Kappa and Lambda Chains and Kappa/Lambda Ratio using PENIA.

Determination of free light chains is used increasingly for patients with multiple myeloma and other plasma cell dyscrasias. The aim of the present study was to define reference intervals for free kappa and lambda chains and kappa/lambda ratio in lithium heparin plasma and compare the test results with cystatin C based estimated glomerular filtration rate. Free kappa and lambda chains were measured in Liheparin plasma from 222 healthy blood donors using free light chain reagents and a BNII nephelometer from Siemens Diagnostics. Calculated reference intervals for kappa chain, free was 4.73 mg/L (90% confidence interval 4.00 - 5.45) - 22.66 mg/L (20.33 - 24.98), for lambda chain, free was 4.33 mg/L (3.70 - 4.95) - 29.28 mg/L (26.96 - 31.59), and for Kappa/Lambda Chain ratio 0.59 (0.56 - 0.62) - 1.46 (1.37 - 1.56). There was no need for gender or age specific reference intervals. Cystatin C based estimated glomerular filtration rate had a significant effect on the levels of free light chains. The study presents reference intervals for plasma free light chains and compared results of estimated glomerular filtration rate with free light chains of kappa and lambda.

Age and gender-specific reference intervals for a panel of lysophosphatidylcholines estimated by tandem mass spectrometry in dried blood spots

Background and objectivesVery long-chain fatty acyl-lysophosphatidylcholines (VLCFA-LysoPCs) are measured in dried blood spots (DBS) for identifying X-linked adrenoleukodystrophy (X-ALD) and other inherited peroxisomal disorders. Our study aimed to establish age- and gender-specific reference intervals for a panel of LysoPCs measured by tandem mass spectrometry in DBS. MethodsLysoPCs (26:0-, 24:0-, 22:0- and 20:0-LysoPCs) were estimated by flow injection analysis-tandem mass spectrometry (FIA-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods in 3.2 mm blood spots of 2689 anonymized, putative normal subjects (1375 males, and 1314 females) aged between 2 days and 65 years. Samples were divided into groups: Neonates (0–1month), Infants (>1m-1year), Children and Adolescents (>1–18years), and Adults (>18years). Reference intervals were determined using the percentile approach and represented as the median with the 1st and 99th percentile lower and upper limits. ResultsThe percentage coefficient of variation (CV) for repeatability assays of internal and external quality control samples were within acceptable limits. Significant differences (P <0.0001, P <0.01) were observed in the concentrations of 26:0-, 24:0-, 22:0- and 20:0-LysoPCs and their ratios, 26:0/22:0-, 24:0/22:0-, 26:0/20:0-and 24:0/20:0-LysoPC in neonates and infants when compared to children, adolescents, and adults. Levels of 26:0-, 24:0- and 22:0-LysoPCs decreased, whereas 20:0-LysoPC increased with age. There were no significant gender-based differences in the concentration of LysoPCs. ConclusionWe established age- and gender-specific reference intervals for a panel of LysoPCs in DBS. These reference values would be helpful when interpreting LysoPC values in DBS during screening for X-ALD and other peroxisomal disorders.

New reference intervals for endocrinological biomarkers in pediatric patients: what can we learn from the LIFE child study?

Abstract Objectives We established reference intervals for serum concentrations of hormones from healthy pediatric subjects and investigated their associations with gender, body mass index (BMI), puberty and oral contraceptives (oC). Methods We calculated reference intervals for the thyroid parameters thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), and calcitonin (Ct); the bone markers osteocalcin, procolagen type 1 N-propeptide, and carboxy-terminal cross-linking telopeptide of type 1 collagen; the calciotropic hormones 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone and the steroids cortisol, progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, estradiol, dehydroepiandrosterone sulfate and aldosterone. Up to 10,002 blood serum samples from 3,229 healthy children and adolescents (age interval: 3 months to 20 years) were measured. To investigate the associations between the hormone levels with age, sex, weight status and the role of puberty-based changes, the measurement and BMI values were transformed into standard deviation scores. Results Most of the hormones depended on age- and gender. Puberty was linked to a, in part, temporary decrease in TSH, FT3 (for females), FT4, Ct, cortisol (for girls) and aldosterone (for boys) and peak in the bone marker and calciotropic hormones (excluding 25(OH)D) and nearly all remaining steroids. BMI had effects on the thyroid, bone, and calciotropic parameters, whereas oC led to increased cortisol, suppressed progesterone and estradiol values. Conclusions Age- and gender-specific reference intervals are essential for the interpretation of pediatric patients’ hormone measurements. Influencing factors as puberty, BMI, or oC should be taken into consideration for diagnosis and treatment monitoring.

Age and Gender-Specific Reference Intervals for Uric Acid Level in Children Aged 5-14 Years in Southeast Zhejiang Province of China: Hyperuricemia in Children May Need Redefinition.

Context: Hyperuricemia is defined when the plasma uric acid concentration is above 416 μmol/L (7 mg/dl) in male adults, or 357 μmol/L (6 mg/dl) in female adults. However, there are no explicit criteria yet for children.Objective: It is necessary to set up reference intervals for the uric acid level in different age groups among children.Materials and Methods: A total of 5,439 individuals (3,258 males, 2,181 females) were included in the final statistical analysis. Reference values of all age groups were determined by statistical descriptions. Multiple linear regression analysis was applied to determine the relationship between uric acid level, BMI, and age.Results: The level of uric acid increased with age. Gender differences in uric acid level occurred after the onset of puberty. Additionally, linear regression revealed a positive correlation between the uric acid level and BMI.Discussion and Conclusion: The reference range of the uric acid level in children is inconsistent with the previous viewpoint. Body mass index plays an important role in uric acid metabolism.

Gender-specific reference intervals for serum prolactin concentrations before and after precipitation by polyethylene glycol

Prolactin, a hormone secreted by the anterior pituitary, exists in three major forms in circulation. The macroprolactin form is biologically inactive but contributes to elevated serum prolactin concentrations. Precipitation of macroprolactin by polyethylene glycol (PEG) is widely used in clinical laboratories for the screening of macroprolactin. The aim of this study was two-fold. Firstly, we sought to establish locally relevant reference intervals for serum prolactin and post-PEG precipitation prolactin concentrations in both genders on the Roche Cobas Prolactin II electrochemiluminescence immunoassay. Secondly, the prolactin concentrations after precipitation by PEG dissolved in phosphate-buffered saline (post-PEG(PBS)) were compared with those after precipitation by PEG dissolved in deionised water (PEG(diH2O)). Prolactin concentrations were measured by using the Prolactin Gen II assay on a Roche Cobas e601 analyser. Recoveries of prolactin after precipitation by PEG in PBS and PEG in diH2O were 64.7%–115.8% and 60.9–100.8%, respectively. Post-PEG (PBS) prolactin concentrations were not statistically different from post-PEG (diH2O) prolactin concentrations in either gender.

Establishment of reference intervals of monomeric prolactin to identify macroprolactinemia in Chinese patients with increased total prolactin

BackgroundMacroprolactin is responsible for pseudohyperprolactinemia and is a common pitfall of the prolactin immunoassay. We aimed to determine the frequency of macroprolactinemia in Chinese hyperprolactinemic patients using monomeric prolactin discriminated by precipitation with polyethylene glycol (PEG).MethodsPost-PEG monomeric prolactin gender-specific reference intervals were established for the Elecsys immunoassay method (Roche Diagnostics) using sera from healthy female (n = 120) and male (n = 120) donors. The reference intervals were validated using 20 macroprolactinemic (as assessed by gel filtration chromatography (GFC)) sera samples, and presence of monomeric prolactin was discriminated by GFC. Patients with high total prolactin were then screened by PEG precipitation to analyze macroprolactin. The demographic and biochemical details of patients with true hyperprolactinemia and macroprolactinemia were compared.ResultsReference intervals for monomeric prolactin in females and males were 3.4–18.5 and 2.7–13.1 ng/mL, respectively. Among 1140 hyperprolactinemic patients, macroprolactinemia was identified in 261 (22.9 %) patients while the other 879 (77.1 %) patients were diagnosed with true hyperprolactinemia. Menstrual disturbances were the most common clinical feature in both groups. Galactorrhea, amenorrhea, and visual disturbances occurred more frequently in true hyperprolactinemic patients (P < 0.05).ConclusionsThe prevalence of macroprolactin in Chinese patients with hyperprolactinemia was described for the first time. Monomeric prolactin concentration, along with a reference interval screening with PEG precipitation, provides a diagnostic approach for hyperprolactinemia with improved accuracy.

Establishment of the reference intervals of lymphocyte subsets for healthy Chinese Han adults and its influencing factors.

BackgroundCellular immune monitoring is becoming more critical in the clinic, but its application has not yet become sufficiently widespread. One reason may be the different reference intervals among clinical laboratories due to several factors. Percentage and number of lymphocyte subsets are standard indicators of cellular immune detection. The present study aimed to establish standardized reference intervals of lymphocyte subsets in the healthy Chinese Han adult population and examine such influencing factors as age, gender, region, and measurement instruments.MethodsA total of 496 healthy Chinese Han people aged 18–59 years from 3 China Mainland regions (north, east, and south) were enrolled. The sample of each center was simultaneously examined by three flow cytometers (FACSCantoTMII, FACSLyricTM, and FACSCaliburTM). A single-platform flow cytometry-based absolute count technique was used to quantify the percentage and number of each lymphocyte subset. The flow cytometry results were analyzed by variance analysis and Z test to determine the influence of age, gender, and instruments on lymphocyte subsets.ResultsMulti-center, age-specific, and gender-specific reference intervals of healthy Chinese Han adults’ lymphocyte subsets were established. There was no statistical difference in the results from the three flow cytometers. Gender affected the results of CD4+ (%) and the absolute count of CD3−CD16+CD56+, where CD4+ (%) was higher in women, and the absolute count of CD3−CD16+CD56+ was higher in men. Age mainly affected the CD4+/CD8+ ratio, which was statistically higher in groups aged over 40 years; the percentage and number of CD3−CD19+ were more elevated in age groups below 30 years; however, the difference was not statistically significant.ConclusionsThis study established the reference intervals of lymphocyte subsets for healthy Chinese Han adult populations under the standardized methods. This study was the first nationwide study in China to use a flow cytometry-based single-platform method to establish the reference intervals of lymphocyte subsets of the healthy Chinese Han adult population. Gender and age were shown to influence the results of lymphocyte subsets.

Indirect reference intervals for haematological parameters in capillary blood of pre-school children.

IntroductionIndirect estimation of reference intervals (RIs) is straightforward and inexpensive procedure for determination of intra-laboratory RIs. We applied the indirect approach to assess RIs for haematological parameters in capillary blood of pre-school children, using results stored in our laboratory database.Materials and methodsWe extracted data from laboratory information system, for the results obtained by automatic haematology analyser in capillary blood of 154 boys and 146 girls during pre-school medical examination. Data distribution was tested, and logarithmic transformation was applied if needed. Reference intervals were calculated by the nonparametric percentile method.ResultsReference intervals were calculated for: RBC count (4.2-5.4 x1012/L), haemoglobin (114-146 g/L), MCH (25.0-29.4 pg), MCHC (321-368 g/L), RDW-SD (36.1-43.5 fL), WBC count (4.5-12.3 x109/L), neutrophils count (1.7-6.9 x109/L) and percentage (29.0-69.0%), lymphocytes count (1.6-4.4 x109/L) and percentage (21.9-60.7%), PLT (165-459 x109/L), MPV (8.1-11.4 fL) and PDW (9.2-14.4%). Gender specific RIs were calculated for monocytes count (male (M): 0.2-1.6 x109/L; female (F): 0.1-1.4 x109/L) and percentage (M: 2.5-18.3%; F: 1.8-16.7%), haematocrit (M: 0.34-0.42 L/L; F: 0.34-0.43 L/L), MCV (M: 73.4-84.6 fL; F: 75.5-84.2 fL) and RDW (M: 12.1-14.3%; F: 11.7-13.9%), due to observed gender differences in these parameters (P = 0.031, 0.028, 0.020, 0.012 and 0.001; respectively). Estimated RIs markedly varied from the literature based RIs that are used in the laboratory.ConclusionsIndirect method employed in this study enables straightforward assessment of RIs in pre-school children. Herein derived RIs differed from the literature-based ones, indicating the need for intra-laboratory determination of RIs for specific populations and sample types.

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.

Establishment of gender specific reference intervals for hepatic enzymes: A pilot study

Reference interval is the common tools used for interpreting various biochemical parameters. The age, gender, diet, ethnicity, socioeconomic conditions affect the physiology of population and thereby affecting the reference intervals. Thus, it is needed to set up our own reference intervals which are specific to particular gender, region and population.To establish the gender specific reference interval for hepatic enzymes at BIMS Hospital, Belagavi.This was a hospital based cross-sectional study involving 450 subjects. The selected subjects were from the general population, health professionals, medical students and those attending the Out-Patient Department (OPD) for general health check ups. The serum Alanine transaminase (ALT), serum Aspartate transaminase (AST), serum Alkaline phosphatase (ALP) were estimated based on the recommendations of IFCC without pyridoxal phosphate and serum Gamma glutamyl transferase (GGT) by enzymatic colorimetric method. The 97.5 percentile and 2.5 percentile was used to obtain the reference intervals.The serum AST and serum GGT showed the statistically significant difference between the male and female values. Thus separate reference should be considered for both males and females. There was no statistically significant difference in serum ALT and serum ALP levels. Thus generalized reference intervals were established.The study revealed the difference in reference intervals of serum AST and serum GGT between males and females.

Longitudinal changes in the dental arches and soft tissue profile of untreated subjects with normal occlusion.

AimThe aim of this study was to analyze dental and soft tissue profile development in children with normal occlusions to establish age- and gender-specific reference intervals for German children during their active growth period.Subjects and methodsThe study group consisted of a sample of 31 untreated Caucasian subjects with normal occlusions. Dental casts were analyzed at four different stages of dentitional development. Extraoral profile photographs were available for 19 subjects at stages T2–T4. In these subjects 11 angular measurements and 14 indices were analyzed. Statistical comparisons of gender-specific differences were performed by Mann–Whitney U tests (p ≤ 0.05).ResultsUpper and lower posterior and total arch perimeters were recorded to be significantly larger in male subjects until the late mixed dentition. Subsequently, there was a tendency toward larger dimensions in males for those parameters. Upper and lower intercanine, interpremolar and intermolar widths were significantly larger in males throughout the entire observation period. There were no statistically significant gender differences with regard to most angular measurements in the dental arches, including molar rotation, palatal volume, overbite, overjet and molar relationship at later dental stages.ConclusionIn untreated subjects with normal occlusion, dental arch and soft tissue parameters can be considered age-dependent. For some dental parameters, gender-specific differences were found that should be taken into consideration during diagnosis and treatment planning of growing children. The obtained longitudinal data of untreated children provide useful information for orthodontic diagnosis, treatment planning and future research projects.