Analytical Bias in the Measurement of Plasma 25-Hydroxyvitamin D Concentrations in Infants

Hypovitaminosis D is prevalent worldwide; however, analytical bias in the measurement of circulating 25-hydroxyvitamin D (25(OH)D) concentrations may affect clinical treatment decisions and research. We performed parallel plasma 25(OH)D analyses using the Abbott Architect i2000 chemiluminescent immunoassay (CIA) and liquid chromatography–tandem mass spectrometry (LC–MS/MS) for paired samples from the same infants at 3 (n = 69), 6 (n = 79) and 12 months (n = 73) of age. To test agreement, we used Lin’s concordance correlation coefficient and corresponding 95% confidence interval, Bland–Altman’s limits of agreement, and Bradley–Blackwood (BB) test. Agreement was high at 3 months (coefficient between difference and mean −0.076; BB F = 0.825; p = 0.440), good at 12 months (−0.25; BB F = 2.41; p = 0.097) but missing at 6 months of age (−0.39; BB F = 12.30; p < 0.001). Overall, 18 infants had disparate results based on the cut-off point for vitamin D deficiency (25(OH)D < 50 nmol/L), particularly at three months, with seven (10%) infants deficient according to CIA but not LC–MS/MS, and four (6%) deficient by LC–MS/MS but not CIA. To our knowledge, this is the first study to show that the reported 25(OH)D concentration may be influenced by both age and assay type. Physicians and researchers should be aware of these pitfalls when measuring circulating 25(OH)D concentrations in infants and when developing treatment plans based on measured vitamin D status.

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Investigating the Role of Functional Polymorphism of Maternal and Neonatal Vitamin D Binding Protein in the Context of 25-Hydroxyvitamin D Cutoffs as Determinants of Maternal-Neonatal Vitamin D Status Profiles in a Sunny Mediterranean Region

Nutrients ◽

10.3390/nu13093082 ◽

2021 ◽

Vol 13 (9) ◽

pp. 3082

Author(s):

Spyridon N. Karras ◽

Erdinç Dursun ◽

Merve Alaylıoğlu ◽

Duygu Gezen-Ak ◽

Cedric Annweiler ◽

...

Keyword(s):

Vitamin D ◽

Mediterranean Region ◽

Binding Protein ◽

Hypovitaminosis D ◽

Vitamin D Status ◽

Vitamin D Binding Protein ◽

Hydroxyvitamin D ◽

High Prevalence ◽

25 Hydroxyvitamin D ◽

Causative Effect

Recent results indicate that dysregulation of vitamin D-binding protein (VDBP) could be involved in the development of hypovitaminosis D, and it comprises a risk factor for adverse fetal, maternal and neonatal outcomes. Until recently, there was a paucity of results regarding the effect of maternal and neonatal VDBP polymorphisms on vitamin D status during pregnancy in the Mediterranean region, with a high prevalence of hypovitaminosis D. We aimed to evaluate the combined effect of maternal and neonatal VDBP polymorphisms and different maternal and neonatal 25-hydroxyvitamin D (25(OH)D) cut-offs on maternal and neonatal vitamin D profile. Blood samples were obtained from a cohort of 66 mother–child pairs at birth. Our results revealed that: (i) Maternal VDBP polymorphisms do not affect neonatal vitamin D status at birth, in any given internationally adopted maternal or neonatal cut-off for 25(OH)D concentrations; (ii) neonatal VDBP polymorphisms are not implicated in the regulation of neonatal vitamin D status at birth; (iii) comparing the distributions of maternal VDBP polymorphisms and maternal 25(OH)D concentrations, with cut-offs at birth, revealed that mothers with a CC genotype for rs2298850 and a CC genotype for rs4588 tended to demonstrate higher 25(OH)D (≥75 nmol/L) during delivery (p = 0.05 and p = 0.04, respectively), after adjustments for biofactors that affect vitamin D equilibrium, including UVB, BMI and weeks of gestation. In conclusion, this study from Southern Europe indicates that maternal and neonatal VDBP polymorphisms do not affect neonatal vitamin D status at birth, whereas mothers with CC genotype for rs2298850 and CC genotype for rs4588 demonstrate higher 25(OH)D concentrations. Future larger studies are required to establish a causative effect of these specific polymorphisms in the attainment of an adequate (≥75 nmol/L) maternal vitamin D status during pregnancy.

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Vitamin D status in pregnant Indian women across trimesters and different seasons and its correlation with neonatal serum 25-hydroxyvitamin D levels

British Journal Of Nutrition ◽

10.1017/s000711451100170x ◽

2011 ◽

Vol 106 (9) ◽

pp. 1383-1389 ◽

Cited By ~ 64

Author(s):

R. K. Marwaha ◽

N. Tandon ◽

S. Chopra ◽

N. Agarwal ◽

M. K. Garg ◽

...

Keyword(s):

Vitamin D ◽

Hypovitaminosis D ◽

First Trimester ◽

Strong Positive Correlation ◽

Vitamin D Status ◽

Second Trimester ◽

Third Trimester ◽

Indian Women ◽

Hydroxyvitamin D ◽

25 Hydroxyvitamin D

The present cross-sectional study was conducted to determine the vitamin D status of pregnant Indian women and their breast-fed infants. Subjects were recruited from the Department of Obstetrics, Armed Forces Clinic and Army Hospital (Research and Referral), Delhi. A total of 541 apparently healthy women with uncomplicated, single, intra-uterine gestation reporting in any trimester were consecutively recruited. Of these 541 women, 299 (first trimester, ninety-seven; second trimester, 125; third trimester, seventy-seven) were recruited in summer (April–October) and 242 (first trimester, fifty-nine, second trimester, ninety-three; third trimester, ninety) were recruited in winter (November–March) to study seasonal variations in vitamin D status. Clinical, dietary, biochemical and hormonal evaluations for the Ca–vitamin D–parathormone axis were performed. A subset of 342 mother–infant pairs was re-evaluated 6 weeks postpartum. Mean serum 25-hydroxyvitamin D (25(OH)D) of pregnant women was 23·2 (sd 12·2) nmol/l. Hypovitaminosis D (25(OH)D < 50 nmol/l) was observed in 96·3 % of the subjects. Serum 25(OH)D levels were significantly lower in winter in the second and third trimesters, while serum intact parathormone (iPTH) and alkaline phosphatase levels were significantly higher in winter in all three trimesters. A significant negative correlation was found between serum 25(OH)D and iPTH in mothers (r − 0·367, P = 0·0001) and infants (r − 0·56, P = 0·0001). A strong positive correlation was observed between 25(OH)D levels of mother–infant pairs (r 0·779, P = 0·0001). A high prevalence of hypovitaminosis D was observed in pregnancy, lactation and infancy with no significant inter-trimester differences in serum 25(OH)D levels.

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Analysis of Suicidal Behavior and Chronicity of Depressive Symptoms in the Presence of Hypovitaminosis D

Current Psychiatry Research and Reviews ◽

10.2174/2666082217666211122155401 ◽

2021 ◽

Vol 17 ◽

Author(s):

Catarina Magalhães Porto ◽

Natalia Santos Barbosa da Silva ◽

Cecília Magalhães Porto Lira ◽

Rayana Porpino Magalhães ◽

José Luiz Oliveira Magalhães ◽

...

Keyword(s):

Vitamin D ◽

Depressive Symptoms ◽

Suicidal Ideation ◽

Depressive Disorder ◽

Suicidal Behavior ◽

Suicide Risk ◽

Hypovitaminosis D ◽

Serum Levels ◽

Hydroxyvitamin D ◽

25 Hydroxyvitamin D

Background: One of the risk factors for suicide includes the presence of depressive disorder and symptoms, which may be related to the reduction of 25-hydroxyvitamin D serum levels. In this scenario, evidence shows vitamin D deficiency as an important aspect, directly related to depressive disorder chronicity. Objective: To assess the association between Vitamin D serum levels and the intensity of depressive symptoms and suicidal behavior in a clinical sample of depressed patients. Methods: A cross-sectional study with 146 patients aged between 18 and 59, seen in two psychiatry ambulatories. Data collection involved measurement of serum 25-hydroxyvitamin D levels and assessment of the intensity of depressive symptoms and suicide risk. Results: In the sample, 35% presented low Vitamin D serum levels and, in these individuals, the incidence of family history of Depressive Disorder (95.2%) and chronicity of severe depressive symptoms (47.8%) was higher. As to suicidal behavior, both groups presented high active suicide risk, with higher rates in the group with hypovitaminosis D. Only suicidal ideation was linked to lower Vitamin D levels (67.4% p= 0,005). Conclusion: In this study, hypovitaminosis D was associated with negative mental health outcomes, such as more severe chronicity of depressive symptoms and suicidal behavior, characterized by active suicidal ideation.

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Hypovitaminosis D in an Italian population of healthy subjects and hospitalized patients

British Journal Of Nutrition ◽

10.1017/s0007114599000264 ◽

1999 ◽

Vol 81 (2) ◽

pp. 133-137 ◽

Cited By ~ 30

Author(s):

Elisabetta Romagnoli ◽

Patrizia Caravella ◽

Liliana Scarnecchia ◽

Paolo Martinez ◽

Salvatore Minisola

Keyword(s):

Vitamin D ◽

Seasonal Variation ◽

Postmenopausal Women ◽

Healthy Subjects ◽

Hypovitaminosis D ◽

Hospitalized Patients ◽

Italian Population ◽

Hydroxyvitamin D ◽

25 Hydroxyvitamin D ◽

Group D

The present study aimed to investigate the prevalence and seasonal variation of hypovitaminosis D (defined as serum 25-hydroxyvitamin D level below 30 nmol/l) among healthy subjects and hospitalized patients living in central Italy. We studied 297 subjects, 131 in February 1997 and 166 in July 1997, subdivided into four groups: (a) young healthy blood donors; (b) healthy postmenopausal women; (c) inpatients with various medical diseases and (d) inpatients engaged in long-term rehabilitation programmes because of various neurological disorders. In all subjects and patients serum levels of 25-hydroxyvitamin D were measured by radioimmunoassay. We found a significant seasonal variation (P< 0·0001) of serum 25-hydroxyvitamin D levels, mean values being higher in summer in all groups, except in patients with a longer hospitalization time (group (d)). In each group, a significantly higher prevalence of hypovitaminosis D was found in winter compared with summer time (P< 0·001), being unexpectedly high in postmenopausal women (winter 32 % and summer 4·5 %); furthermore, in both seasons, inpatients were characterized by the highest incidences of hypovitaminosis, particularly those in group (d) (winter 82·3 % and summer 57·8 %). The results of the present study emphasize the importance of 25-hydroxyvitamin D measurement, and the need to increase vitamin D intake in Italy; foodstuff fortification and supplement use must be considered in order to prevent negative effects of vitamin D deficiency on skeletal integrity.

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Vitamin D Metabolism and Profiling in Veterinary Species

Metabolites ◽

10.3390/metabo10090371 ◽

2020 ◽

Vol 10 (9) ◽

pp. 371 ◽

Cited By ~ 1

Author(s):

Emma A. Hurst ◽

Natalie Z. Homer ◽

Richard J. Mellanby

Keyword(s):

Vitamin D ◽

Companion Animals ◽

Vitamin D Metabolites ◽

Vitamin D Status ◽

Vitamin D Metabolism ◽

Hydroxyvitamin D ◽

Chromatography Tandem Mass Spectrometry ◽

Liquid Chromatography Tandem Mass ◽

Health And Disease ◽

25 Hydroxyvitamin D

The demand for vitamin D analysis in veterinary species is increasing with the growing knowledge of the extra-skeletal role vitamin D plays in health and disease. The circulating 25-hydroxyvitamin-D (25(OH)D) metabolite is used to assess vitamin D status, and the benefits of analysing other metabolites in the complex vitamin D pathway are being discovered in humans. Profiling of the vitamin D pathway by liquid chromatography tandem mass spectrometry (LC-MS/MS) facilitates simultaneous analysis of multiple metabolites in a single sample and over wide dynamic ranges, and this method is now considered the gold-standard for quantifying vitamin D metabolites. However, very few studies report using LC-MS/MS for the analysis of vitamin D metabolites in veterinary species. Given the complexity of the vitamin D pathway and the similarities in the roles of vitamin D in health and disease between humans and companion animals, there is a clear need to establish a comprehensive, reliable method for veterinary analysis that is comparable to that used in human clinical practice. In this review, we highlight the differences in vitamin D metabolism between veterinary species and the benefits of measuring vitamin D metabolites beyond 25(OH)D. Finally, we discuss the analytical challenges in profiling vitamin D in veterinary species with a focus on LC-MS/MS methods.

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Vitamin D Dosing Strategies Among Jordanians With Hypovitaminosis D

Journal of Pharmacy Practice ◽

10.1177/0897190015626334 ◽

2016 ◽

Vol 30 (2) ◽

pp. 172-179 ◽

Cited By ~ 1

Author(s):

Nahla Khawaja ◽

Mohammed Liswi ◽

Mohammed El-Khateeb ◽

Dana Hyassat ◽

Dalila Bajawi ◽

...

Keyword(s):

Body Mass Index ◽

Vitamin D ◽

Hypovitaminosis D ◽

Hydroxyvitamin D ◽

Dosing Strategies ◽

Optimal Maintenance ◽

Group A ◽

25 Hydroxyvitamin D ◽

The Mean ◽

Group B

Objective: To compare between weekly and daily cholecalciferol in patients with hypovitaminosis D and to determine the optimal maintenance dose. Methods: Seventy-one volunteers with hypovitaminosis D were randomly assigned to 2 dose regimens: cholecalciferol 50 000 IU weekly for 8 weeks, then 50 000 IU monthly for 2 months (group A) and 7000 IU daily for 8 weeks, then 12 500 IU weekly for 2 months (group B). Cholecalciferol was stopped for 2 months and reintroduced as 50 000 IU bimonthly for group A and 50 000 IU monthly for group B. Results: Two months after therapy, the mean serum 25-hydroxyvitamin D (25(OH)D) level increased from 11.4 to 51.2 ng/mL and from 11.7 to 44.9 ng/mL in groups A and B, respectively ( P = .065). The levels of 25(OH)D declined similarly in both groups during maintenance and after holding therapy. After resuming cholecalciferol, 25(OH)D levels increased to 33.8 and 28.8 ng/mL in groups A and B, respectively ( P = .027). There was a negative correlation between serum 25(OH)D levels and body mass index (BMI; P = .040). Conclusion: Timing and frequency of the dosing (daily vs weekly) have no effect on the rise in serum 25(OH)D levels as long as the accumulative dose of cholecalciferol is similar. Cholecalciferol 50 000 IU bimonthly is required to maintain sufficient 25(OH)D levels.

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Influence of Vitamin D Binding Protein on Accuracy of 25-Hydroxyvitamin D Measurement Using the ADVIA Centaur Vitamin D Total Assay

International Journal of Endocrinology ◽

10.1155/2014/691679 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12

Author(s):

James Freeman ◽

Kimberly Wilson ◽

Ryan Spears ◽

Victoria Shalhoub ◽

Paul Sibley

Keyword(s):

Vitamin D ◽

Healthy Subjects ◽

Binding Protein ◽

Reference Method ◽

Total Serum ◽

Vitamin D Binding Protein ◽

Hydroxyvitamin D ◽

Liquid Chromatography Tandem Mass ◽

25 Hydroxyvitamin D ◽

Different Populations

Vitamin D status in different populations relies on accurate measurement of total serum 25-hydroxyvitamin D [25(OH)D] concentrations [i.e., 25(OH)D3and 25(OH)D2]. This study evaluated agreement between the ADVIA Centaur Vitamin D Total assay for 25(OH)D testing (traceable to the NIST-Ghent reference method procedure) and a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for various populations with different levels of vitamin D binding protein (DBP). Total serum 25(OH)D concentrations were measured for 36 pregnant women, 40 hemodialysis patients, and 30 samples (DBP-spiked or not) from healthy subjects. ELISA measured DBP levels. The mean serum DBP concentrations were higher for pregnancy (415 μg/mL) and lower for hemodialysis subjects (198 μg/mL) than for healthy subjects and were highest for spiked serum (545 μg/mL). The average bias between the ADVIA Centaur assay and the LC-MS/MS method was −1.4% (healthy), −6.1% (pregnancy), and 4.4% (hemodialysis). The slightly greater bias for samples from some pregnancy and hemodialysis subjects with serum DBP levels outside of the normal healthy range fell within a clinically acceptable range—reflected by analysis of their low-range (≤136 μg/mL), medium-range (137–559 μg/mL), and high-range (≥560 μg/mL) DBP groups. Thus, the ADVIA Centaur Vitamin D Total assay demonstrates acceptable performance compared with an LC-MS/MS method for populations containing different amounts of DBP.

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The importance of assays in vitamin D status classification: a comparison of four automated 25-hydroxyvitamin D immunoassays

LaboratoriumsMedizin ◽

10.1515/labmed-2012-0074 ◽

2013 ◽

Vol 37 (5) ◽

Cited By ~ 6

Author(s):

Johannes Schmid ◽

Katharina Kienreich ◽

Martin Gaksch ◽

Martin Grübler ◽

Reinhard Raggam ◽

...

Keyword(s):

Vitamin D ◽

Pearson Correlation ◽

Critical Evaluation ◽

Assay Method ◽

Vitamin D Status ◽

Hydroxyvitamin D ◽

25 Hydroxyvitamin D ◽

Status Classification ◽

Abbott Architect ◽

Roche Cobas

AbstractOwing to a growing interest in vitamin D, there has been an increasing demand for 25-hydroxyvitamin D (25[OH]D) measurements over the past few years warranting a critical evaluation of laboratory methods for 25(OH)D determinations. Therefore, the aim of this study was to compare four of the most frequently used routine assays for 25(OH)D.In 106 hypertensive patients (53±14 years; 59% females), derived from the Graz Endocrine Causes of Hypertension (GECOH) study, we measured 25(OH)D in serum and plasma by means of four automated immunoassays (DiaSorin Liaison, IDS iSYS, Abbott ARCHITECT, and Roche Cobas).We observed a poor comparability between assay results with Pearson correlation coefficients between the different methods ranging from 0.57 to 0.85. Using a value of ≤20 ng/mL (50 nmol/L) as the cut-off for vitamin D deficiency, the percentages of vitamin D deficient patients was significantly different depending on the assay method: 79.2% (Abbott ARCHITECT), 50.0% (DiaSorin Liaison), 28.3% (IDS iSYS), and 23.6% (Roche Cobas).By comparing four frequently used automated immunoassays for 25(OH)D, we observed remarkable differences with a significant impact on vitamin D status classification. Clinicians and researchers must be aware of these assay differences and must aim for standardization of 25(OH)D measurements.

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Surveillance evaluation of the standardization of assay values for serum total 25-hydroxyvitamin D concentration in Japan

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/0004563218765570 ◽

2018 ◽

Vol 55 (6) ◽

pp. 647-656 ◽

Cited By ~ 2

Author(s):

Hiroshi Ihara ◽

Sachiko Kiuchi ◽

Takayuki Ishige ◽

Motoi Nishimura ◽

Kazuyuki Matsushita ◽

...

Keyword(s):

Vitamin D ◽

Pilot Study ◽

Surveillance Study ◽

Serum Samples ◽

Acceptance Criterion ◽

Average Percentage ◽

Hydroxyvitamin D ◽

Consensus Values ◽

Liquid Chromatography Tandem Mass ◽

25 Hydroxyvitamin D

Background To assess the vitamin D nutritional status, serum total 25-hydroxyvitamin D (25(OH)D) concentration is measured. We used six automated 25(OH)D immunoassays (AIAs) available in Japan and certified by the Vitamin D Standardization Program (VDSP) at the U.S. Center for Disease Control and Prevention to assess the concordance of the assay results. Methods Serum total 25(OH)D concentrations in SRM 972a and 20 serum samples from patients were determined using three liquid chromatography-tandem mass spectrometry (LC-MS/MS) and six AIAs (pilot study), and an additional 110 serum samples were assessed by the six AIAs (surveillance study). The assay bias from the results of LC-MS/MS by Chiba University or consensus values (i.e. average of six AIAs) was estimated using the procedure described in CLSI document EP09-A3. Results LC-MS/MS at Chiba University could completely separate 25(OH)D2, 25(OH)D3 and 3-epi-25(OH)D3, and the observed values including total 25(OH)D in SRM 972a were all within ±1·SD of the assigned values. All AIAs produced results greater than ±3·SD. In the pilot study, four of the six AIAs had an average percentage bias, as estimated by confidence interval (CI), larger than ±5% (acceptance criterion in CLSI); the bias converged from −6.5% to 3.2% after adjustment by LC-MS/MS. In the surveillance study, 25(OH)D concentrations in AIAs all adjusted to LC-MS/MS converged within ±5% from consensus values. However, some AIAs showed negative or positive bias from the consensus values. Conclusions Current AIAs in Japan continue to lack standardization. Manufacturers should implement quality assurance strategies so that their values more closely align to those of standard reference material 972a.

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Controversies in Vitamin D: Summary Statement From an International Conference

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2018-01414 ◽

2018 ◽

Vol 104 (2) ◽

pp. 234-240 ◽

Cited By ~ 44

Author(s):

Andrea Giustina ◽

Robert A Adler ◽

Neil Binkley ◽

Roger Bouillon ◽

Peter R Ebeling ◽

...

Keyword(s):

Vitamin D ◽

Hypovitaminosis D ◽

Vitamin D Metabolites ◽

Vitamin D Metabolism ◽

International Conference ◽

Hydroxyvitamin D ◽

Disease States ◽

25 Hydroxyvitamin D ◽

Total Body ◽

Definition Of

Abstract Context Vitamin D is classically recognized as a regulator of calcium and phosphorus metabolism. Recent advances in the measurement of vitamin D metabolites, diagnosis of vitamin D deficiency, and clinical observations have led to an appreciation that along with its role in skeletal metabolism, vitamin D may well have an important role in nonclassical settings. Measurement of the circulating form of vitamin D that best describes total body stores, namely 25-hydroxyvitamin D, can be unreliable despite many sophisticated methodologies that have been proposed and implemented. Likewise, evidence from clinical studies showing a beneficial role of vitamin D in different disease states has been controversial and at times speculative. Moreover, the target concentrations of 25-hydroxyvitamin D to address a number of putative links between vitamin D inadequacy and nonskeletal diseases are further areas of uncertainty. Setting To address these issues, an international conference on “Controversies in Vitamin D” was held in Pisa, Italy, in June 2017. Three main topics were addressed: (i) vitamin D assays and the definition of hypovitaminosis D; (ii) skeletal and extraskeletal effects of vitamin D; (iii) therapeutics of vitamin D. Results This report provides a summary of the deliberations of the expert panels of the conference. Conclusions Despite great advances in our appreciation of vitamin D metabolism, measurements, biological actions on classical and nonclassical tissues, and therapeutics, all of which this report summarizes, much more work remains to be done so that our knowledge base can become even more secure.

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