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.

Interlaboratory variation for NT-proBNP among Swedish laboratories in an external quality program 2011-2021.

OBJECTIVES: NT-proBNP is frequently used for ruling out heart failure. Different cut-offs are used depending on the clinical context, e.g. an acute or chronic condition. Medical decision limits have been suggested at 125 and 300 ng/L or 400 ng/L in international guidelines. However, there is limited standardization between NT-proBNP methods and using the same blood sample might cause different treatment of patients. METHODS: Data from the external quality assessment program for NT-proBNP from Equalis, Sweden, were extracted for the period 2011-2021, and categorized according to manufacturer. Manufacturer median NT-proBNP values were compared to total median values. CV% was calculated for each manufacturer and in comparison to different levels of NT-proBNP. RESULTS: Roche was the most common method, and its median results were closest to the median consensus results. When looking at the total CV at NT-proBNP levels in the range of 0-500 ng/L, the total CV varied from 4 to 27%. During 2019-2021, Siemens (Immulite, Centaur, Atellica) yielded results 16-20% above the consensus median depending on sample level. Similarly, Abbott was 5-7% above, while Roche and Siemens Stratus were 1% respectively 6-10% below the consensus median. CONCLUSIONS: The introduction of new manufacturers and methods in 2017 have caused the agreement between manufacturers to decline. This highlights the need for a common calibrator and reference materials, particularly since medical decision limits in guidelines, e.g. European Society of Cardiology 2021, which are mostly based on Roche methods, do not take these method differences into account.

The complexity of kidney disease and diagnosing it - cystatin C, selective glomerular hypofiltration syndromes and proteome regulation.

Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous glomerular filtration rate (GFR)-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by the identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterized by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules <1 kDa dominating the glomerular filtrate, for example water, urea and creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterized by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.

Vitamin D status in children and adults in Sweden: dietary intake and 25-hydroxyvitamin D concentrations in children aged 10-12 years and adults aged 18-80 years.

The study aimed to estimate vitamin D intake and plasma/serum 25-hydroxyvitamin D (25(OH)D) concentrations, investigate determinants of 25(OH)D concentrations and compare two 25(OH)D assays. We conducted two nationwide cross-sectional studies in Sweden with 206 school children aged 10-12 years and 1797 adults aged 18-80 years (n 268 provided blood samples). A web-based dietary record was used to assess dietary intake. Plasma/serum 25(OH)D was analysed by liquid chromatography-mass spectrometry (LC-MS) and immunoassay in adults and LC-MS/MS in children. Most participants reported a vitamin D intake below the average requirement (AR), 16 % of children and 33 % of adults met the AR (7⋅5 µg). In adults, plasma 25(OH)D below 30 and 50 nmol/l were found in 1 and 18 % of participants during the summer period and in 9 and 40 % of participants during the winter period, respectively. In children, serum 25(OH)D below 30 and 50 nmol/l were found in 5 and 42 % of participants (samples collected March-May), respectively. Higher 25(OH)D concentrations were associated with the summer season, vacations in sunny locations (adults), and dietary intake of vitamin D and use of vitamin D supplements, while lower concentrations were associated with a higher BMI and an origin outside of Europe. Concentrations of 25(OH)D were lower using the immunoassay than with the LC-MS assay, but associations with dietary factors and seasonal variability were similar. In conclusion, vitamin D intake was lower than the AR, especially in children. The 25(OH)D concentrations were low in many participants, but few participants had a concentration below 30 nmol/l.

Hemolysis interference in 10 coagulation assays on an instrument with viscosity-based, chromogenic, and turbidimetric clot detection.

INTRODUCTION: Hemolysate in plasma samples from patients may cause misleading results in coagulation assays. Even though modern coagulation instruments often are equipped with modules that can detect hemolysis, icterus, and lipemia (HIL), studies that report the influence of these interferences are still limited. The present paper focuses on the influence of hemolysis on 10 coagulation assays. METHODS: Artificial hemolysis was created by freezing/thawing, and the hemolysates generated were added to pools of patient plasma. Pathological and normal levels were pooled separately. These spiked samples were analyzed on a STA R Max 2 instrument. The coagulation assays evaluated utilize clot, chromogenic, or immunoturbidimetric detection. RESULTS: Four of the evaluated assays were not influenced by hemolysis: fibrinogen, von Willebrand factor antigen, activated partial thromboplastin time, and factor VIII. Interestingly, normal and slightly elevated prothrombin time (INR < 2.0) was insensitive to hemolysis, whereas samples with a high INR (≥2.0) exhibited falsely high readings. The assays for antithrombin and fibrin D-dimer displayed an intermediate sensitivity to hemolysis. The most sensitive assay turned out to be anti-Xa, followed by protein C and protein S. For the anti-Xa assay, the results are decreased by 10% already at 0.5 g/L hemoglobin. CONCLUSION: The present study shows that hemolysis affects several of commonly used coagulation assays. Since the sensitivity for hemolysis is dependent on the brand of the assay as well as the instrument and principle of measurement, it is necessary to evaluate the influence of each specific combination.

Lower creatinine concentration values and lower inter-laboratory variation among Swedish hospital laboratories in 2014 compared to 1996: results from the Equalis external quality assessment program.

Background Creatinine measurement for estimation of glomerular filtration rate (GFR) is a frequently used laboratory test. Differences in analytic creatinine methods have caused large inter-laboratory variation. International and national standardization efforts have been made in the last decade. Methods This study describes the results of the standardization efforts in Sweden by summarizing data for creatinine concentration in blood plasma in the Equalis quality assessment program during 1996-2014. Results Non-compensated Jaffe methods dominated in 1996-2001 (91 of 103 laboratories; 90%) and were then gradually replaced by either compensated Jaffe methods or enzymatic creatinine methods. In 2014 a majority of Swedish hospital laboratories (139 of 159; 87%) used enzymatic methods. The reported mean creatinine value by the Swedish laboratories was about 10 µmol/L higher than the isotope dilution mass spectrometry (IDMS) assured reference value in 2003, but consistent with the reference value from 2009 to 2014. The inter-laboratory CV was 7%-9% for creatinine values until 2007, and thereafter gradually decreased to about 4%-5% in 2014. Conclusions The introduction of enzymatic methods in Swedish laboratories has contributed to achieving a low inter-laboratory variation. Also, the reported values are lower for enzymatic methods compared to Jaffe methods, and the values obtained with enzymatic methods were consistent with IDMS certified values established at reference laboratories. Thus, many Swedish hospital laboratories reported 10 µmol/L lower, and more true, creatinine concentrations in 2012 than in 2003, which may cause bias in longitudinal studies.

Age- and sex-specific reference values for non-HDL cholesterol and remnant cholesterol derived from the Nordic Reference Interval Project (NORIP).

OBJECTIVES: Non-HDL-cholesterol (non-HDL-C) has been reported to be a better marker of cardiovascular risk than LDL-cholesterol (LDL-C) especially in individuals with high triglyceride values. Further, levels of remnant cholesterol have been suggested to in part explain residual risk not captured with LDL-C. The aim of the present study was to define reference values for non-HDL-C and remnant cholesterol based on data from the Nordic Reference Interval Project (NORIP). METHODS: We analyzed the test results for total cholesterol, HDL-cholesterol and triglycerides from 1392 healthy females and 1236 healthy males. Non-HDL-C was calculated as measured total cholesterol minus measured HDL-cholesterol. Remnant cholesterol was calculated using the Friedewald equation for LDL-C: measured total cholesterol minus measured HDL-cholesterol and minus calculated LDL-cholesterol. The 2.5th and 97.5th percentiles for these markers were calculated according to the International Federation of Clinical Chemistry guidelines on the statistical treatment of reference values. RESULTS: Age (18-<30, 30-49 and ≥50 years) and sex-specific reference intervals were calculated for non-HDL-cholesterol and remnant-cholesterol. Levels of non-HDL-C and remnant cholesterol differed between sex and age strata. CONCLUSIONS: Age- and sex-specific reference intervals should be used for the triglyceride rich lipid variables non-HDL-C and remnant cholesterol. Since these markers may add information on risk burden beyond LDL-C, our hope is that these reference intervals will aid the introduction of automatic reporting of non-HDL-C by hospital laboratories.

Pediatric reference intervals for general clinical chemistry components - merging of studies from Denmark and Sweden.

BACKGROUND: Reference intervals are crucial tools aiding clinicians when making medical decisions. However, for children such values often are lacking or incomplete. The present study combines data from separate pediatric reference interval studies of Denmark and Sweden in order to increase sample size and to include also pre-school children who were lacking in the Danish study. METHODS: Results from two separate studies including 1988 healthy children and adolescents aged 6 months to 18 years of age were merged and recalculated. Eighteen general clinical chemistry components were measured on Abbott and Roche platforms. To facilitate commutability, the NFKK Reference Serum X was used. RESULTS: Age- and gender-specific pediatric reference intervals were defined by calculating 2.5 and 97.5 percentiles. CONCLUSION: The data generated are primarily applicable to a Nordic population, but could be used by any laboratory if validated for the local patient population.

Digoxin and Mortality in Patients With Atrial Fibrillation.

BACKGROUND: Digoxin is widely used in patients with atrial fibrillation (AF). OBJECTIVES: The goal of this paper was to explore whether digoxin use was independently associated with increased mortality in patients with AF and if the association was modified by heart failure and/or serum digoxin concentration. METHODS: The association between digoxin use and mortality was assessed in 17,897 patients by using a propensity score-adjusted analysis and in new digoxin users during the trial versus propensity score-matched control participants. The authors investigated the independent association between serum digoxin concentration and mortality after multivariable adjustment. RESULTS: At baseline, 5,824 (32.5%) patients were receiving digoxin. Baseline digoxin use was not associated with an increased risk of death (adjusted hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 0.96 to 1.23; p = 0.19). However, patients with a serum digoxin concentration ≥1.2 ng/ml had a 56% increased hazard of mortality (adjusted HR: 1.56; 95% CI: 1.20 to 2.04) compared with those not on digoxin. When analyzed as a continuous variable, serum digoxin concentration was associated with a 19% higher adjusted hazard of death for each 0.5-ng/ml increase (p = 0.0010); these results were similar for patients with and without heart failure. Compared with propensity score-matched control participants, the risk of death (adjusted HR: 1.78; 95% CI: 1.37 to 2.31) and sudden death (adjusted HR: 2.14; 95% CI: 1.11 to 4.12) was significantly higher in new digoxin users. CONCLUSIONS: In patients with AF taking digoxin, the risk of death was independently related to serum digoxin concentration and was highest in patients with concentrations ≥1.2 ng/ml. Initiating digoxin was independently associated with higher mortality in patients with AF, regardless of heart failure.

Perfluoroalkyl acid levels in first-time mothers in relation to offspring weight gain and growth.

We investigated if maternal body burdens of perfluoroalkyl acids (PFAAs) at the time of delivery are associated with birth outcome and if early life exposure (in utero/nursing) is associated with early childhood growth and weight gain. Maternal PFAA body burdens were estimated by analysis of serum samples from mothers living in Uppsala County, Sweden (POPUP), sampled three weeks after delivery between 1996 and 2011. Data on child length and weight were collected from medical records and converted into standard deviation scores (SDS). Multiple linear regression models with appropriate covariates were used to analyze associations between maternal PFAA levels and birth outcomes (n=381). After birth Generalized Least Squares models were used to analyze associations between maternal PFAA and child growth (n=200). Inverse associations were found between maternal levels of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), and birth weight SDS with a change of -0.10 to -0.18 weight SDS for an inter-quartile range (IQR) increase in ng/g PFAA. After birth, weight and length SDS were not significantly associated with maternal PFAA. However, BMI SDS was significantly associated with PFOA, PFNA, and PFHxS at 3 and 4years of age, and with PFOS at 4 and 5years of age. If causal, these associations suggest that PFAA affects fetal and childhood body development in different directions.

Dietary intake and biomarker status of folate in Swedish adults.

PURPOSE: National data on folate status are missing in Sweden, and regional data indicate folate insufficiency in up to more than 25% of the study populations. The objectives were to determine folate intake and status in the adult Swedish population as well as identifying dietary patterns associated with beneficial folate status. METHODS: Folate intake was estimated using a web-based 4-d food record in adults aged 18-80 years (n = 1797). Folate status was measured as erythrocyte (n = 282) and plasma folate concentrations (n = 294). Factor analysis was used to derive a dietary pattern associated with a higher folate status. RESULTS: Median folate intake was 246 µg/day (Q 1 = 196, Q 3 = 304, n = 1797) and for women of reproductive age 227 µg/day (Q 1 = 181, Q 3 = 282, n = 450). As dietary folate equivalents (DFE), median intake was 257 µg/day (Q 1 = 201, Q 3 = 323) and for women of reproductive age 239 µg/day (Q 1 = 185, Q 3 = 300). Low blood folate concentrations were found in 2% (erythrocyte concentrations <317 nmol/L) and 4% (plasma concentrations <6.8 nmol/L) of the participants, respectively. None of the women of reproductive age had erythrocyte folate concentrations associated with the lowest risk of neural tube defects. Dietary patterns associated with higher folate status were rich in vegetables, pulses and roots as well as cheese and alcoholic beverages, and low in meat. CONCLUSIONS: Prevalence of low erythrocyte folate concentrations was low in this population, and estimated dietary intakes are well above average requirement. However, to obtain a folate status optimal for prevention of neural tube defects major dietary changes are required and folic acid supplements recommended prior to conception.

Albumin adjustment of total calcium does not improve the estimation of calcium status.

BACKGROUND: There is a longstanding controversy as to whether plasma measurements of total calcium should be adjusted for albumin concentration, and if so which formulas are the most appropriate. METHODS: Ionised calcium, total calcium and albumin results, analysed at the same time at Uppsala University Hospital Laboratory between February 2005 and June 2013, were retrieved from a laboratory information system. The dataset included results from 20,003 patients. Total calcium was albumin-modified by a locally derived formula, based on 3106 patients from the dataset, and formulas from the literature. The agreement between the reference method ionised calcium and unadjusted total calcium and the seven different albumin-modifying calcium formulas, respectively, were compared with intra-class correlation coefficients (ICC). RESULTS: Total calcium showed substantial agreement to ionised calcium, ICC 0.85 (95% CI 0.84-0.86) for the whole validation cohort. Albumin-modified calcium by different formulas showed significantly less or equal agreement, however the locally determined formula performed better than formulas taken from the literature. Also, total calcium classified the patient as hypo-normo- or hypercalcemic right in 82% of the patients. The albumin-modified calcium did not classify patients significantly better except in the subgroup hypoalbuminemia (<30 g/L) where the local formula classified the patients slightly better than total calcium. CONCLUSIONS: Albumin modification of total calcium determinations is unlikely to add valuable information, and this practice should be abandoned. Ionised calcium should be used more frequently when aberrant results for total calcium are followed up, or in patients with known hypoalbuminemia.

Serum levels of brominated flame retardants (BFRs: PBDE, HBCD) and influence of dietary factors in a population-based study on Swedish adults.

The aim of this study was to investigate associations between serum concentrations of brominated flame retardants and personal characteristics, including diet, in adults participating in a population-based study in Sweden 2010-11. Moreover, observed concentrations were used in a health risk assessment, using published health-based reference values. Serum samples of 170 adult individuals of both sexes were analyzed for 10 PBDE congeners and HBCD by GC-MS. When including concentrations between LOD and LOQ, highest median serum concentration was observed for BDE-153 (1.2 ng/g serum lipid), followed by BDE-209 (0.95 ng/g lipid), BDE-47 (0.49 ng/g lipid) and BDE-100 (0.21 ng/g lipid). Median concentration of HBCD was 0.10 ng/g lipid. A few markedly elevated concentrations of BDE-209, HBCD (77-78 ng/g lipid) and BDE-47 (44 ng/g lipid) were observed. The only statistical significant findings were higher BDE-153 concentrations in men than in women, and positive associations between serum BDE-153 concentrations and consumption of fish (total), beef, mutton and poultry. PBDE concentrations were in accordance with concentrations reported in other European countries but generally lower than those found in North America. Median PBDE serum concentrations observed in adults from Sweden suggest sufficient health protection, when compared with published health-based reference values, although some outliers with high serum concentrations had lower safety margins.

Reference values for 34 frequently used laboratory tests in 80-year-old men and women.

OBJECTIVES: Reference values are usually based on blood samples from healthy individuals in the age range 20-50 years. Most patients seeking health care are older than this reference population. Many reference intervals are age dependent and there is thus a need to have appropriate reference intervals also for elderly individuals. METHODS: We analyzed a group of frequently used laboratory tests in an 80-year-old population (n=531, 266 females and 265 males). The 2.5th and 97.5th percentiles for these markers were calculated according to the International Federation of Clinical Chemistry guidelines on the statistical treatment of reference values. RESULTS: Reference values are reported for serum alanine transaminase (ALT), albumin, alkaline phosphatase, pancreatic amylase, apolipoprotein A1, apolipoprotein B, apolipoprotein B/apolipoprotein A1 ratio, aspartate aminotransferase (AST), AST/ALT ratio, bilirubin, calcium, calprotectin, cholesterol, HDL-cholesterol, creatinine kinase (CK), creatinine, creatinine estimated GFR, C-reactive protein, cystatin C, cystatin C estimated GFR, gamma-glutamyltransferase (GGT), iron, iron saturation, lactate dehydrogenase (LDH), magnesium, phosphate, transferrin, triglycerides, urate, urea, zinc, hemoglobin, platelet count and white blood cell count. The upper reference limit for creatinine and urea was significantly increased while the lower limit for iron and albumin was decreased in this elderly population in comparison with the population in the Nordic Reference Interval Project (NORIP). CONCLUSIONS: Reference values calculated from the whole population and a subpopulation without cardiovascular disease showed strong concordance. Several of the reference interval limits were outside the 90% confidence interval of NORIP.

Cystatin C Predicts Incident Cardiovascular Disease in Twins.

BACKGROUND: Cystatin C is associated with both renal function and atherosclerotic cardiovascular disease (ASCVD). We have previously shown a genetic correlation between cystatin C and prevalent ASCVD. The objective of this article is to study whether variation in cystatin C or creatinine predicts incident ASCVD when controlled for genetic factors. METHODS AND RESULTS: The predictive value of cystatin C and creatinine for incident ASCVD was studied in 11 402 Swedish twins, free of CVD at baseline, in an adjusted Cox-regression model during a median follow-up of 71 months. Twin pairs discordant for incident stroke, myocardial infarction and ASCVD during follow-up were identified and within-pair comparisons regarding cystatin C and creatinine levels were performed. We also investigated whether contact frequency and degree of shared environment influences were associated with similarity in cystatin C levels. In univariate analysis, cystatin C predicted incident ASCVD hazard ratio 1.57, 95% CI 1.47-1.67. When adjusted for traditional Framingham risk factors as covariates, cystatin C remained a predictor of incident stroke hazard ratio 1.45, 95% CI (1.25-1.70), ASCVD hazard ratio 1.26, 95% CI (1.13-1.41), and myocardial infarction hazard ratio 1.16, 95% CI (1.01-1.33). In twins discordant for incident stroke, cystatin C at baseline was higher in the twin who experienced a stroke compared to the healthy co-twin (1.11±0.3 mg/L versus 1.06±0.3 mg/L), whereas creatinine was lower in the twin who developed CVD compared to their healthy co-twins (76.1±16.9 µmol/L versus 79.4±20.3 µmol/L). CONCLUSIONS: Variation in cystatin C relates to incident ASCVD and to stroke when adjusted for genetic confounding. In identical twins, cystatin C may be a sensitive marker of early hypertensive end-organ damage and small-vessel disease, whereas creatinine level may reflect nutritional status. The findings in disease-discordant monozygotic twins indicate that unique, possibly preventable, environmental factors are important.

Relative validation of the dietary intake of fatty acids among adults in the Swedish National Dietary Survey using plasma phospholipid fatty acid composition.

The aims of a national dietary study are several-fold. One purpose is to monitor the intake of foods and nutrients in the population and to compare intakes with dietary recommendations. It is, however, difficult to measure dietary fat intake and plasma biomarker fatty acid (FA) composition may be used as an objective measure of dietary fat intake. Thus, the relative ability of a diet record to capture habitual fat intake was validated against biomarker FA. Dietary fat intake was measured in a novel self-assisted web-based 4-d food record - the 'Riksmaten' method. Spearman rank correlations between dietary FA, certain food groups (fish-shellfish, dairy products, meat and sausages, and spreads) and the fat content of these food groups and biomarker FA were explored. Participants were 150 women and 129 men, aged 18-80 years, who took part in the Swedish National Dietary Survey, Riksmaten adults 2010-11. Blood samples were collected on average 20 d after the diet record and FA composition was measured in plasma phospholipids by GLC. Total n-3 FA (r 0·31), EPA (r 0·34) and DHA (r 0·42) were correlated between plasma and diet (all P ≤ 0·001). Adjustment for covariates attenuated the relationships. Linoleic acid was only marginally correlated (r 0·15; P = 0·06) in women. Plasma pentadecaenoic acid and heptadecaenoic acid were correlated with dairy product intake as previously reported. In conclusion, the Riksmaten method appears valid for the purpose of collecting data on dietary fat composition, at least in a healthy adult population.

Population-Based Pediatric Reference Intervals in General Clinical Chemistry: A Swedish Survey.

Very few high quality studies on pediatric reference intervals for general clinical chemistry and hematology analytes have been performed. Three recent prospective community-based projects utilising blood samples from healthy children in Sweden, Denmark and Canada have substantially improved the situation. The Swedish survey included 701 healthy children. Reference intervals for general clinical chemistry and hematology were defined.

Reference intervals for parathyroid hormone for 70-year-old males and females: exclusion of individuals from the reference interval based on sex, calcium, diabetes, cardiovascular diseases or reduced kidney function has limited effects on the interval.

BACKGROUND: A problem when producing reference intervals for elderly individuals is that they often suffer from a number of diseases and they are most often on medication. If all such persons are excluded, there is a risk that the residual subgroup may not be representative of the population, we therefore wanted to compare the effects different exclusion criteria has on the reference intervals. METHODS: We measured parathyroid hormone (PTH), calcium, albumin and cystatin C in a cohort of 70-year-old males and females (n=1003). Reference intervals for PTH for males and females were calculated for the entire population and after exclusion of persons with calcium >2.60 mmol/L, calcium >2.51 mmol/L, diabetes, reduced glomerular filtration rate (GFR), and cardiovascular diseases. RESULTS: The calculated PTH reference interval 16 (CI 14-17) to 94 (CI 87-101) ng/L. Exclusion of study subjects resulted in smaller reference sample groups, but the reference limits remained within the 90% confidence intervals of the original reference limits. The selections thus had a very limited effect on the calculated reference interval for PTH. CONCLUSIONS: Exclusion of elderly individuals with high calcium concentrations, diabetes, reduced GFR or cardiovascular disease has little effect on the reference interval for PTH. It is better not to exclude these individuals, as it will provide a broader base for the reference interval.

Alkaline phosphatase in healthy children: reference intervals and prevalence of elevated levels.

BACKGROUND: Transient hyperphosphatasemia (TH) is an often unnoticed benign entity, primarily affecting children below 5 years of age. However, the prevalence among healthy children is unknown. We used data from a Swedish pediatric reference interval project to estimate the prevalence of high alkaline phosphatase (ALP) among healthy children and to calculate pediatric reference intervals. METHODS: Blood was collected from 699 subjectively healthy children aged 6 months to 18 years. After exclusion of subjects with high ALP, age- and gender-specific reference intervals were calculated. RESULTS: Six children had ALP levels >16.7 µkat/l (>1,000 U/l), including 4 females and 2 males aged 7-22 months. The prevalence in the age group from 6 months to 2 years was 6.2% (6/97). None of the older children had levels of ALP >16.7 µkat/l. The study did not include the follow-up of these apparently healthy children. Consequently, conditions others than TH explaining the elevated ALP could not be excluded. However, general chemistry analyses, such as liver enzymes, calcium, intact PTH and vitamin D, were essentially normal in these children. CONCLUSIONS: The prevalence of high ALP among subjectively healthy children was approximately 2.4% below 5 years of age and 6.2% below 2 years. Reference intervals vary with age and gender.