Vitamin D: Analytical Advances, Clinical Impact, and Ongoing Debates on Health Perspectives.

BACKGROUND: Vitamin D, acknowledged since the 1930s for its role in preventing rickets, gained additional prominence in relation to fragility fracture prevention in the late 1980s. From the early 2000s, connections between vitamin D deficiency and extra-skeletal pathologies emerged, alongside increased awareness of widespread deficits. This prompted crucial debates on optimal serum concentrations, expected to conclude when the outcomes of high-dose supplementation randomized controlled trials were available. Skepticism arose with inconclusive results from these trials. CONTENT: This review begins with an exploration of vitamin D metabolism, followed by a detailed description of the measurement of vitamin D metabolites and the crucial role of standardization. Subsequent sections focus on the association of vitamin D with bone health and explore the extra-skeletal effects. The review concludes with a comprehensive discussion on the definition of vitamin D status and its implications for supplementation. SUMMARY: Despite standardization efforts, assay variations and challenges still exist, especially in specific patient groups. Vitamin D supplementation has a significant impact on bone metabolism and optimal vitamin D status improves the efficacy of antiresorptive drugs such as bisphosphonates. The extra-skeletal effects of vitamin D remain debated, but may include potential benefits in conditions such as respiratory infections and cancer mortality, particularly in deficient individuals. The definition of vitamin D sufficiency is nuanced, especially when variations in population groups and analytical methods are taken into account. Despite ongoing debates and recent mega-trials tempering enthusiasm, vitamin D remains a complex and essential element in human health. Further research is needed to clarify its role in various health outcomes and guide supplementation strategies.

Serum calcium normal range in 1000 term newborns.

INTRODUCTION: Serum calcium rapidly declines at birth because of the sudden interruption of the maternal-fetal calcium influx. Several factors are known to influence serum calcium in the first days of life, including circulating concentrations of maternal vitamin D. Objective was to establish the normal range variations of neonatal serum calcium according to the French current vitamin D supplementation during pregnancy, i.e. 100,000 IU of cholecalciferol during the third trimester. METHODS: We included in our prospective cohort study 1002 mother-newborn dyads from, with recruitments from April 2012 to July 2014 in France, in two recruiting centers located in Paris neighborhoods. RESULTS: Total serum calcium at 3 days of life in neonates varied from 2.06 to 2.73 mmol/L [2.5 and 97.5 percentiles], with a mean of 2.45 mmol/L. Serum calcium was similar between babies born from vitamin D supplemented mothers and those born from the non-supplemented ones. Univariate and multivariable analyses demonstrated the importance of maternal and cord blood 25(OH)D concentrations for newborn serum calcium maintenance. CONCLUSION: We established that the expected serum calcium in neonates ranges between 2.06 and 2.73 mmol/L which is significantly wider than the adult range. This finding should help physicians in the diagnosis of hypo- or hypercalcemia. In addition, our study supports the importance of vitamin D supplementation and 25(OH)D status for neonatal serum calcium maintenance.

Reference values for serum calcium in neonates should be established in a population of vitamin D-replete subjects.

INTRODUCTION: Serum calcium is frequently measured during the neonatal period, and is known to be influenced by the vitamin D status. We hypothesized that the 25OHD concentration may influence the lower limit of the serum calcium normal range in neonates. METHODS: We included in our prospective cohort study 1002 mother-newborn pair recruited from April 2012 to July 2014, in two centers located in the neighborhoods of Paris, France, whose serum calcium was measured at 3 days of life. We established, after exclusion of outliers, a 95% confidence interval (CI) for serum calcium 1) in our whole population of 1002 neonates, 2) in neonates with a cord blood 25OHD concentration ≥ 30 nmol/L, and 3) in those with a 25OHD ≥ 50 nmol/L. RESULTS: The mean serum total calcium was 2.46 ± 0.13 nmol/L [95% CI: 2.19-2.72 mmol/L], 2.47 ± 0.25 mmol/L [95% CI: 2.22-2.72 mmol/L], and 2.50 ± 0.25 mmol/L [95% CI: 2.25-2.75 mmol/L] in the whole group, in the 514 neonates with 25OHD ≥ 30 nmol/L, and in the 202 neonates with 25OHD ≥ 50 nmol/L respectively. The lower limit of the 95% range was significantly higher in neonates with 25 OHD ≥ 30 nmol/L (p<0.05) and ≥ 50 nmol/L (p<0.001) than in the entire cohort. CONCLUSION: We show that the lower limit of the normal serum calcium range is higher in groups with a higher 25OHD than in unselected subjects. We propose that the reference range for serum calcium in neonates is 2.25 to 2.75 mmol/L.

Pubertal origin of growth retardation in inborn errors of protein metabolism: A longitudinal cohort study.

OBJECTIVES: Inherited amino-acid metabolism disorders (IAAMDs) require lifelong protein-restricted diet. We aimed to investigate: 1/ whether IAAMDs was associated with growth, pubertal, bone mineral apparent density (BMAD) or body composition impairments; 2/ associations linking height, amino-acid mixture (AAM), plasma amino-acids and IGF1 concentrations. DESIGN: Retrospective longitudinal study of 213 patients with neonatal-onset urea cycle disorders (UCD,n = 77), organic aciduria (OA,n = 89), maple syrup urine disease (MSUD,n = 34), or tyrosinaemia type 1 (n = 13). METHODS: We collected growth parameters, pubertal status, BMAD, body composition, protein-intake, and IGF1 throughout growth. RESULTS: Overall final height (n = 69) was below target height (TH): -0.9(1.4) vs. -0.1(0.9) SD, p < 0.001. Final height was ≤ TH-2SD in 12 (21%) patients. Height ≤ - 2SD was more frequent during puberty than during early-infancy and pre-puberty: 23.5% vs. 6.9%, p = 0.002; and vs. 10.7%, p < 0.001. Pubertal delay was frequent (26.7%). Height (SD) was positively associated with isoleucine concentration: ß, 0.008; 95%CI, 0.003 to 0.012; p = 0.001. In the pubertal subgroup, height (SD) was lower in patients with vs. without AAM supplementation: -1.22 (1.40) vs. -0.63 (1.46) (p = 0.02). In OA, height and median (IQR) isoleucine and valine concentrations(µmol/L) during puberty were lower in patients with vs. without AAM supplementation: -1.75 (1.30) vs. -0.33 (1.55) SD, p < 0.001; and 40 (23) vs. 60 (25) (p = 0.02) and 138 (92) vs. 191 (63) (p = 0.01), respectively. No correlation was found with IGF1. Lean-mass index was lower than fat-mass index: -2.03 (1.15) vs. -0.44 (0.89), p < 0.001. CONCLUSIONS: In IAAMDs, growth retardation worsened during puberty which was delayed in all disease subgroups. Height seems linked to the disease, AAM composition and lower isoleucine concentration, independently of the GH-IGF1 pathway. We recommend close monitoring of diet during puberty.

Unveiling a new era with liquid chromatography coupled with mass spectrometry to enhance parathyroid hormone measurement in patients with chronic kidney disease.

Precise determination of circulating parathyroid hormone (PTH) concentration is crucial to diagnose and manage various disease conditions, including the chronic kidney disease-mineral and bone disorder. However, the lack of standardization in PTH assays is challenging for clinicians, potentially leading to medical errors because the different assays do not provide equivalent results and use different reference ranges. Here, we aimed to evaluate the impact of recalibrating PTH immunoassays by means of a recently developed LC-MS/MS method as the reference. Utilizing a large panel of pooled plasma samples with PTH concentrations determined by the LC-MS/MS method calibrated with the World Health Organization (WHO) 95/646 International Standard, five PTH immunoassays were recalibrated. The robustness of this standardization was evaluated over time using different sets of samples. The recalibration successfully reduced inter-assay variability with harmonization of PTH measurements across different assays. By recalibrating the assays based on the WHO 95/646 International Standard, we demonstrated the feasibility for standardizing PTH measurement results and adopting common reference ranges for PTH assays, facilitating a more consistent interpretation of PTH values. The recalibration process aligns PTH results obtained from various immunoassays with the LC-MS/MS method, providing more consistent and reliable measurements. Thus, establishing true standardization across all PTH assays is crucial to ensure consistent interpretation and clinical decision-making.

Nonskeletal and skeletal effects of high doses versus low doses of vitamin D3 in renal transplant recipients: Results of the VITALE (VITamin D supplementation in renAL transplant recipients) study, a randomized clinical trial.

Vitamin D sufficiency is associated with a reduced risk of fractures, diabetes mellitus, cardiovascular events, and cancers, which are frequent complications after renal transplantation. The VITALE (VITamin D supplementation in renAL transplant recipients) study is a multicenter double-blind randomized trial, including nondiabetic adult renal transplant recipients with serum 25-hydroxy vitamin D (25(OH) vitamin D) levels of <30 ng/mL, which is randomized 12 to 48 months after transplantation to receive high (100 000 IU) or low doses (12 000 IU) of cholecalciferol every 2 weeks for 2 months and then monthly for 22 months. The primary outcome was a composite endpoint, including diabetes mellitus, major cardiovascular events, cancer, and death. Of 536 inclusions (50.8 [13.7] years, 335 men), 269 and 267 inclusions were in the high-dose and low-dose groups, respectively. The serum 25(OH) vitamin D levels increased by 23 versus 6 ng/mL in the high-dose and low-dose groups, respectively (P < .0001). In the intent-to-treat analysis, 15% versus 16% of the patients in the high-dose and low-dose groups, respectively, experienced a first event of the composite endpoint (hazard ratio, 0.94 [0.60-1.48]; P = .78), whereas 1% and 4% of patients in the high-dose and low-dose groups, respectively, experienced an incident symptomatic fracture (odds ratio, 0.24 [0.07-0.86], P = .03). The incidence of adverse events was similar between the groups. After renal transplantation, high doses of cholecalciferol are safe but do not reduce extraskeletal complications (trial registration: ClinicalTrials.gov; identifier: NCT01431430).

Cholecalciferol (vitamin D3) must not be considered as an endocrine disruptor / Le cholécalciférol (la vitamine D3) ne doit pas être inclus dans la liste des perturbateurs endocriniens

A French ministerial decree planning to include cholecalciferol, i.e. vitamin D3 (VD3), in the endocrine disruptors (ED) list has generated a lot of concerns in French physicians and scientists. The aim of the present article was to discuss the scientific rationale that may support or not this decision, which seems to be due to the use of VD3 overdose as a rodenticide in some European countries. First, it is noticeable that cholecalciferol is not an "exogenous substance", a term used in all the definitions of ED, as it is largely synthesized in the skin after UVB rays exposure. Second, we did not find any published article that may support the inclusion of VD3 in the ED list. The request "vitamin D AND endocrine disruptor" reported 33 references in the PubMed database on March, 10, 2022, most of them discussing disturbances of vitamin D metabolism by EDs. Third, a large amount of studies conclude that VD3 has or may have beneficial effects on many functions that are known to be altered by EDs. In addition, we warn that learning that VD3 could be legally considered as a PE may cause the general public to mistrust vitamin D supplementation, which is not desirable in terms of public health as it may increase the already too high prevalence of vitamin D deficient individuals. We consider the aberrant decision of including cholecalciferol in the ED list should be rapidly invalidated before being effective in France and possibly disseminated in the European Union.

Un projet d'arrêté ministériel inscrivant le cholécalciférol, c'est-à-dire la vitamine D3 (VD3), dans la liste des perturbateurs endocriniens (PE) est à l'origine de débats en France. L'objectif de notre article était de préciser les arguments scientifiques pour et contre l'inscription de la VD3 dans la liste des PE, qui semble être initialement due à son utilisation à très forte dose comme raticide/rodenticide dans certains pays. Premièrement, le cholécalciférol ne peut être défini comme une substance exogène, terme utilisé dans les différentes définitions des PE, car il est largement synthétisé dans la peau suite à l'exposition aux UVB. Deuxièmement, il n'existe aucune publication dans la base de données PubMed en faveur d'une inscription de la VD3 dans la liste des PE. La requête « vitamin D AND endocrine disruptor ¼ retrouvait 33 références au 10 mars 2022, la plupart évoquant des perturbations du métabolisme de la vitamine D par les PE. Troisièmement, un grand nombre d'études concluent, au contraire, que la VD3 a des effets bénéfiques sur de nombreuses fonctions altérées par les PE. Plus largement, nous alertons sur le fait qu'apprendre que la VD3 pourrait être règlementairement considérée comme un PE pourrait occasionner, auprès du grand public, une défiance vis-à-vis de la supplémentation en vitamine D, ce qui n'est pas souhaitable en termes de santé publique car de nature à aggraver la prévalence déjà trop élevée des individus carencés en vitamine D. Il est encore temps d'éviter cette décision aberrante et non fondée.

IGF-I Variability Over Repeated Measures in Patients With Acromegaly Under Long-Acting Somatostatin Receptor Ligands.

CONTEXT: In patients with acromegaly on long-term treatment with long-acting somatostatin receptor ligands (SRLs), the time of blood collection for IGF-I measurement after injection is not well defined. OBJECTIVE: We aimed to assess serum IGF-I dynamics and variability in SRL-treated patients compared with surgically cured patients and healthy controls. METHODS: Thirty patients under SRLs considered controlled based on a normal previous IGF-I level, 10 patients cured by pituitary surgery, and 7 healthy subjects underwent 4 weekly IGF-I determinations. RESULTS: In SRL-treated patients, the IGF-I SDS (mean ±â€…SD) was higher just before injection (0.34 ±â€…0.66) than at Day 7 (-0.33 ±â€…0.61; P = 0.0041) and Day 14 (-0.23 ±â€…0.60; P = 0.047) after injection, but it did not significantly vary in cured patients and healthy controls. The IGF-I CV was higher in SRL-treated patients than in cured patients or healthy controls (14.4 ±â€…7.6% vs 7.9 ±â€…4.4% and 8.3 ±â€…3.2%, respectively; P < 0.05 for both). Among SRL-treated patients, IGF-I CV was higher in "nonoptimally controlled patients"-i.e., patients with at least one elevated IGF-I value out of 4 (n = 9) compared with "optimally controlled" patients for whom all 4 IGF-I SDS values were < 2.0 (21.3 ±â€…9.3 vs 11.6 ±â€…6.0%; P = 0.0019). The latter did not differ from surgically cured patients and healthy controls. The measurement at the farthest distance from the SRL injection was the most predictive of patients with nonoptimally controlled disease. CONCLUSION: In patients treated with long-acting SRLs, IGF-I sampling at the farthest distance from SRL injection is the most informative and best predictor of optimal disease control.

High-dose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial.

BACKGROUND: Vitamin D supplementation has been proposed as a treatment for Coronavirus Disease 2019 (COVID-19) based on experimental data and data from small and uncontrolled observational studies. The COvid19 and VITamin d TRIAL (COVIT-TRIAL) study was conducted to test whether a single oral high dose of cholecalciferol (vitamin D3) administered within 72 hours after the diagnosis of COVID-19 improves, compared to standard-dose cholecalciferol, the 14-day overall survival among at-risk older adults infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). METHODS AND FINDINGS: This multicenter, randomized, controlled, open-label, superiority trial involved collaboration of 9 medical centers in France. Patients admitted to the hospital units or living in nursing homes adjacent to the investigator centers were eligible if they were ≥65 years, had SARS-CoV-2 infection of less than 3 days, and at least 1 COVID-19 worsening risk factor (among age ≥75 years, SpO2 ≤94%, or PaO2/FiO2 ≤300 mm Hg). Main noninclusion criteria were organ failure requiring ICU, SpO2 ≤92% despite 5 L/min oxygen, life expectancy <3 months, vitamin D supplementation >800 IU/day during the preceding month, and contraindications to vitamin D supplements. Eligible and consenting patients were randomly allocated to either a single oral high-dose (400,000 IU) or standard-dose (50,000 IU) cholecalciferol administered under medical supervision within 72 hours after the diagnosis of COVID-19. Participants and local study staff were not masked to the allocated treatment, but the Steering Committee and the Data and Safety Monitoring Board were masked to the randomization group and outcome data during the trial. The primary outcome was 14-day overall mortality. Between April 15 and December 17, 2020, of 1,207 patients who were assessed for eligibility in the COVIT-TRIAL study, 254 met eligibility criteria and formed the intention-to-treat population. The median age was 88 (IQR, 82 to 92) years, and 148 patients (58%) were women. Overall, 8 (6%) of 127 patients allocated to high-dose cholecalciferol, and 14 (11%) of 127 patients allocated to standard-dose cholecalciferol died within 14 days (adjusted hazard ratio = 0.39 [95% confidence interval [CI], 0.16 to 0.99], P = 0.049, after controlling for randomization strata [i.e., age, oxygen requirement, hospitalization, use of antibiotics, anti-infective drugs, and/or corticosteroids] and baseline imbalances in important prognostic factors [i.e., sex, ongoing cancers, profuse diarrhea, and delirium at baseline]). The number needed to treat for one person to benefit (NNTB) was 21 [NNTB 9 to ∞ to number needed to treat for one person to harm (NNTH) 46]. Apparent benefits were also found on 14-day mortality due to COVID-19 (7 (6%) deaths in high-dose group and 14 (11%) deaths in standard-dose group; adjusted hazard ratio = 0.33 [95% CI, 0.12 to 0.86], P = 0.02). The protective effect of the single oral high-dose administration was not sustained at 28 days (19 (15%) deaths in high-dose group and 21 (17%) deaths in standard-dose group; adjusted hazard ratio = 0.70 [95% CI, 0.36 to 1.36], P = 0.29). High-dose cholecalciferol did not result in more frequent adverse effects compared to the standard dose. The open-label design and limited study power are the main limitations of the study. CONCLUSIONS: In this randomized controlled trial (RCT), we observed that the early administration of high-dose versus standard-dose vitamin D3 to at-risk older patients with COVID-19 improved overall mortality at day 14. The effect was no longer observed after 28 days. TRIAL REGISTRATION: ClinicalTrials.gov NCT04344041.

Bone Fragility in Chronic Kidney Disease Stage 3 to 5: The Use of Vitamin D Supplementation.

Frequently silent until advanced stages, bone fragility associated with chronic kidney disease-mineral and bone disease (CKD-MBD) is one of the most devastating complications of CKD. Its pathophysiology includes the reduction of active vitamin D metabolites, phosphate accumulation, decreased intestinal calcium absorption, renal alpha klotho production, and elevated fibroblast growth factor 23 (FGF23) levels. Altogether, these factors contribute firstly to secondary hyperparathyroidism, and ultimately, to micro- and macrostructural bone changes, which lead to low bone mineral density and an increased risk of fracture. A vitamin D deficiency is common in CKD patients, and low circulating 25(OH)D levels are invariably associated with high serum parathyroid hormone (PTH) levels as well as with bone mineralization defects, such as osteomalacia in case of severe forms. It is also associated with a variety of non-skeletal diseases, including cardiovascular disease, diabetes mellitus, multiple sclerosis, cancer, and reduced immunological response. Current international guidelines recommend supplementing CKD patients with nutritional vitamin D as in the general population; however, there is no randomized clinical trial (RCT) evaluating the effect of vitamin D (or vitamin D+calcium) supplementation on the risk of fracture in the setting of CKD. It is also unknown what level of circulating 25(OH)D would be sufficient to prevent bone abnormalities and fractures in these patients. The impact of vitamin D supplementation on other surrogate endpoints, including bone mineral density and bone-related circulating biomarkers (PTH, FGF23, bone-specific alkaline phosphatase, sclerostin) has been evaluated in several RTCs; however, the results were not always translated into an improvement in long-term outcomes, such as reduced fracture risk. This review provides a brief and comprehensive update on CKD-related bone fragility and the use of natural vitamin D supplementation in these patients.

Vitamin D supplementation and COVID-19: expert consensus and guidelines.

After 12 months of viral circulation, the SARS-CoV-2 has infected millions of people around the world, leaving hundreds of thousands dead. Given the lack of effective therapy and vaccination against COVID-19, focusing on the immediate repurposing of existing drugs gives some hope of curbing the pandemic. Vitamin D is a possible candidate drug which is discussed in a high number of publications. Randomised clinical trials have shown that vitamin D supplementation significantly reduces the risk of respiratory infections. There is also a great deal of evidence that hypovitaminosis D is an independent (and easily modifiable) risk factor for severe forms of COVID-19 and death. Vitamin D supplementation is a simple, safe and inexpensive measure, which is effective in correcting hypovitaminosis D, present in 40-50% of the French population and in more than 80% of adults with COVID-19. In this position paper, we propose simple regimens (adapted to the pharmaceutical forms currently available in France) for vitamin D supplementation in adults with or without COVID-19.

Reference values for IGF-I serum concentration in an adult population: use of the VARIETE cohort for two new immunoassays.

OBJECTIVE: Measurement of IGF-I is important in the management of patients with growth hormone disorders. Here we aim to establish normative data for two new IGF-I assay kits based on a large random sample of the French general adult population. SUBJECTS AND METHODS: We measured IGF-I in 911 healthy adults (18-90 years) with two immunoassays (ROCHE Elecsys® and IMMULITE-2000 calibrated against the new IS 02/2547). We compared the data with those of the six immunoassays (iSYS, LIAISON XL, IMMULITE-2000 calibrated against the first IS 87/518, IGF-I RIACT, Mediagnost ELISA, and Mediagnost RIA) that we reported previously. The pairwise concordance among the eight assays was assessed with Bland-Altman plots for both the IGF-1 raw data and the standard deviation scores (SDS), as well as with the percentage of observed agreement and the weighted Kappa coefficient for categorizing IGF-I SDS (ClinicalTrials.gov Identifier: NCT01831648). RESULTS: The normative data included the range of values (2.5-97.5 percentiles) given by the two new IGF-I assays according to age group and sex. A formula for the SDS calculation is provided. As for the previous six assays, the lower limits of the reference intervals of the two new assays were similar, but the upper limits varied markedly. The pairwise concordances were only moderate (kappa 0.57). CONCLUSIONS: Data obtained for these two new IGF-I immunoassays confirm that despite being obtained in the same large healthy population, the reference intervals of the eight commercial IGF-1 assay kits showed noteworthy differences. The agreement among the various methods was moderate to good.

Bone Status According to Neurofibromatosis Type 1 Phenotype: A Descriptive Study of 60 Women in France.

There is an increased risk of osteoporosis and an abnormal bone turn over in neurofibromatosis 1 (NF1). Our objective is to evaluate bone status in NF1 and to look for associations with cutaneous phenotype. We conducted a descriptive, monocentric study. We included 60 NF1 women, 18-51 years old, non-menopausal, divided in 2 groups: «at risk phenotype¼ (ARP) composed by 30 patients with at least 2 subcutaneous neurofibromas (SC-NF) and «classical phenotype¼ (CP) composed by 30 patients with none or 1 SC-NF. We evaluated low bone mineral density (BMD) risk factors and measured BMD, calcium and phosphorus homeostasis and bone turnover markers. Before 50 years old, Z-score has to be used to assess BMD. Z-score < - 2 is below expected range and represents 2.5% of the population. There was no difference between the two groups. Overall, Z-scores were low and 5 patients had a Z-score < - 2 (8.3%), which is 3 times general population low BMD frequency. 10 fragility fractures occurred in 8 patients, among which 2 were vertebral fractures. 85% had low calcium intake. 12 patients had hypophosphoremia, 25 elevated PTH. Vitamin D levels were low for 86.4%. 41 patients (69.5%) had at least one abnormal bone turnover markers. Low BMD is 3.3 times more frequent in NF1 than in general population, with high fracture risk, regardless of the skin phenotype, classical or at risk, because of high bone turn over and secondary hyperparathyroidism due to vitamin D deficiency and poor calcium intake.

Relationship between vitamin D status in the first trimester of pregnancy and gestational diabetes mellitus - A nested case-control study.

BACKGROUND & AIMS: Gestational diabetes mellitus (GDM) is one of the most frequent medical complications during pregnancy. It has been associated with many adverse pregnancy, fetal and neonatal outcomes, as well as with an increased risk for mothers and children in the long term. There is a growing interest in vitamin D and its potential role in the development of metabolic disorders. However, the medical literature is not consensual. The aim of this study was to assess the risk of GDM according to vitamin D status during the first trimester. METHODS: This study is a nested case-control study performed from a multicenter prospective observational cohort of pregnant women assessed for 25-hydroxyvitamin D levels (25OHD). Three hundred ninety-three patients were included in the initial cohort. After applying exclusion criteria, a total of 1191 pregnant women were included. Two hundred fifty women with GDM (cases) were matched to 941 women without GDM (controls) for parity, age, body mass index before pregnancy, the season of conception, and phototype. This study was funded by a grant from the "Programme Hospitalier de Recherche Publique 2010". RESULTS: The GDM risk was significantly greater for patients with 25OHD levels <20 ng/mL (OR = 1∙42, 95% CI 1∙06-1∙91; p = 0∙021). However, there was no significant relationship with other thresholds. The study of 25OHD levels with the more precise cutting of 5 units intervals showed a variable relationship with GDM risk, as the risk was low for very low 25OHD levels, increased for moderated levels, decreased for normal levels, and finally increased for higher levels. CONCLUSION: According to our study, there seems to be no linear relationship between GDM and 25OHD levels in the first trimester of pregnancy since GDM risk does not continuously decrease as 25OHD concentrations increase. Our results most probably highlight the absence of an association between 25OHD levels and GDM risk.

[Vitamin D supplementation and COVID-19: expert consensus and guidelines]. / Supplémentation en vitamine D et Covid-19 : consensus d'experts et recommandations.

After 12 months of viral circulation, the SARS-CoV-2 has infected millions of people around the world, leaving hundreds of thousands dead. With the lack of effective therapy and vaccination against COVID-19, focusing on the immediate repurposing of existing drugs gives hope of curbing the pandemic. Vitamin D is a possible candidate discussed in a high amount of publications. Randomized clinical trials show that vitamin D supplementation significantly reduces the risk of respiratory infections. There are also many evidences that hypovitaminosis D is an independent (and easily modifiable) risk factor for severe forms of COVID-19 and death. Vitamin D supplementation is a simple, safe and inexpensive measure, which is effective in correcting hypovitaminosis D found in 40-50% of the French population and in more than 80% of adults with COVID-19. In this position paper, we propose simple regimens (adapted to the pharmaceutical forms currently available in France) for vitamin D supplementation in adults with or without COVID-19.

Vitamin D and pregnancy outcomes: Overall results of the FEPED study.

Vitamin D insufficiency is highly prevalent in children and adults including pregnant women. During pregnancy, maternal vitamin D insufficiency could increase risks of several pregnancy complications and adverse birth outcomes. The FEPED study was designed to assess the effects of maternal vitamin D status in the first trimester during pregnancy on risks of preeclampsia, gestational diabetes mellitus (GDM), preterm birth and small-for-gestational age (SGA) at birth. This observational prospective cohort included 3129 women with a singleton pregnancy between April 2012 and July 2014 in six maternity units in France and Belgium. The aim of this review is to summarize the results of the FEPED study. At the first trimester the mean 25(OH)D concentration was 21.9 ± 10.4 ng/mL and 25(OH)D concentration was <20 ng/mL in 46.5 % of patients. After matching 83 cases of preeclampsia with 319 controls, a significant decrease in the risk of preeclampsia was associated with maternal vitamin D levels ≥ 30 ng/mL in the third trimesters (OR = 0.34; 95 % CI: 0.13-0.86. P = 0.023). In the first trimester, the risk for preeclampsia was decreased in these patients, but did not achieve statistical significance (OR = 0.57 95 % CI, 0.30-1.01; p = 0.09). For the 250 cases with GDM matched with 941 controls, no linear relationship was found between GDM and 25OHD levels in the first trimester of pregnancy. Finally, 2813 pregnant women were included in analyses of risks of preterm and SGA birth. No association was found between low maternal vitamin D levels in the first trimester and the risks of preterm birth (aOR = 1.53; 95 % CI: 0.97-2.43) or SGA (aOR = 1.07; 95 % CI: 0.75-1.54). Further investigation is needed to understand the mechanisms behind the association between vitamin D and birth outcomes.