Serum 25OHD Concentrations Research Articles

Retraction notice to "Changes in the supporting muscles of the fractured hip in elderly women".

There is little information concerning the changes in the muscles supporting the fractured hip joint. Morphologic and histochemical examinations of biopsy specimen from the middle gluteal muscles were performed at surgery in 42 elderly women with hip fracture caused by a fall. On the basis of serum 25-hydroxyvitamin D (25-OHD) concentration, the patients were divided into a sufficient group (25-OHD concentration >39 nmol/L, n = 20) and a deficient group (25-OHD concentration <39 nmol/L, n = 22). Reflecting the muscular trauma in the fall-induced hip fracture, the following pathologic changes were common in both the sufficient and deficient groups: degenerating and regenerating fibers; fiber necrosis; and inflammatory reaction. The mean type II fiber diameter in the deficient group (15.4 ± 4.2 μm) was significantly smaller than that in the sufficient group (38.7 ± 8.1 μm) (p < 0.0001). In the deficient group, the mean type II fiber diameter correlated with the serum 25-OHD concentration (r = 0.714, p = 0.0011). This correlation was not observed in the sufficient group. Low physical activity along with vitamin D deficiency prior to the hip fractures may have caused the severe type II fiber atrophy in the deficient group. Such changes may weaken the support of the hip joint and lead to falls. We believe that severe type fiber II atrophy is an independent risk factor for hip fractures and this should be studied in a classic case-control study. Severe type II fiber atrophy may also have contributed to the poor functional outcome in the deficient group. Further research is needed to develop treatments and rehabilitation protocols that might improve gait and body function by attenuating type II fiber atrophy.

Vitamin D and Delirium in Older Adults: A Case-Control Study in Geriatric Acute Care Unit.

Objective: Vitamin D is involved in brain health and function. Our objective was to determine whether the serum 25-hydroxyvitamin D (25OHD) concentration was associated with delirium in a case-control study of geriatric inpatients.Methods: Sixty cases with delirium (mean ± SD, 84.8 ± 5.7years; 58.3% female) and 180 age- and gender-matched controls were enrolled in a geriatric acute care unit between 2012 and 2014. The diagnosis of delirium was made using the Confusion Assessment Method. Hypovitaminosis D was defined using consecutively the consensual threshold value of 50 nmol/L and a threshold value calculated from a sensitivity-specificity analysis. Age, gender, number of acute diseases, use of psychoactive drugs, season of testing, and serum concentrations of calcium, parathyroid hormone, creatinine, albumin, TSH, vitamin B9 and vitamin B12 were used as potential confounders.Results: The 60 cases with delirium exhibited lower 25OHD concentration than 180 matched controls (35.4 ± 30.0 nmol/L vs. 45.9 ± 34.5 nmol/L, p = 0.035). Increased 25OHD concentration was associated with a decrease in delirium prevalence (OR = 0.99 [95CI: 0.98–0.99] per nmol/L of 25OHD, p = 0.038). The concentration distinguishing between cases and controls with the best sensitivity-specificity was found between 29.5 and 30.5 nmol/L. The regression models showed that delirium was associated with hypovitaminosis D defined either as 25OHD ≤ 50 nmol/L (OR = 2.37 [95CI: 1.07–5.25], p = 0.034) or as 25OHD ≤ 30 nmol/L (OR = 2.66 [95 CI: 1.30–5.45], p = 0.008).Conclusions: Decreased serum 25OHD concentrations were associated with delirium among acute geriatric inpatients. The threshold concentration to differentiate between cases and controls was around 30 nmol/L.

“Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study”

ObjectiveThe vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly increase serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19. DesignParallel pilot randomized open label, double-masked clinical trial. SettingUniversity hospital setting (Reina Sofia University Hospital, Córdoba Spain.) Participants76 consecutive patients hospitalized with COVID-19 infection, clinical picture of acute respiratory infection, confirmed by a radiographic pattern of viral pneumonia and by a positive SARS-CoV-2 PCR with CURB65 severity scale (recommending hospital admission in case of total score > 1). ProceduresAll hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every 12 h on the first day, and 200 mg every 12 h for the following 5 days), azithromycin (500 mg orally for 5 days. Eligible patients were allocated at a 2 calcifediol:1 no calcifediol ratio through electronic randomization on the day of admission to take oral calcifediol (0.532 mg), or not. Patients in the calcifediol treatment group continued with oral calcifediol (0.266 mg) on day 3 and 7, and then weekly until discharge or ICU admission. Outcomes of effectiveness included rate of ICU admission and deaths. ResultsOf 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50 %) p value X2 Fischer test p < 0.001. Univariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment versus without Calcifediol treatment: 0.02 (95 %CI 0.002−0.17). Multivariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment vs Without Calcifediol treatment ICU (adjusting by Hypertension and T2DM): 0.03 (95 %CI: 0.003-0.25). Of the patients treated with calcifediol, none died, and all were discharged, without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, two died and the remaining 11 were discharged. ConclusionOur pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease, but larger trials with groups properly matched will be required to show a definitive answer.

Baseline Vitamin D Status, Sleep Patterns, and the Risk of Incident Type 2 Diabetes in Data From the UK Biobank Study.

Circulating vitamin D concentrations have been associated with the risk of type 2 diabetes (T2D), but the results are inconsistent. Emerging evidence suggests that vitamin D metabolism is linked to sleep behaviors. We investigated the prospective association between serum 25-hydroxyvitamin D (25OHD) and the risk of incident T2D and whether such association was modified by sleep behaviors. The study included 350,211 individuals free of diabetes in the UK Biobank. Serum 25OHD (nmol/L) concentrations were measured. Five sleep behaviors including sleep duration, insomnia, snoring, chronotype, and daytime sleepiness were included to generate overall sleep patterns, defined by healthy sleep scores. We also calculated genetic risk scores of sleep patterns. During a median follow-up of 8.1 years, we documented 6,940 case subjects with incident T2D. We found that serum 25OHD was significantly associated with a lower risk of incident T2D, and the multivariate adjusted hazard ratio (HR) (95% CI) per 10 nmol/L increase was 0.88 (0.87-0.90). We found a significant interaction between 25OHD and overall sleep patterns on the risk of incident T2D (P for interaction = 0.002). The inverse association between high 25OHD and T2D was more prominent among participants with healthier sleep patterns. Among the individual sleep behaviors, daytime sleepiness showed the strongest interaction with 25OHD (P for interaction = 0.0006). The reduced HR of T2D associated with high 25OHD appeared to be more evident among participants with no frequent daytime sleepiness compared with those with excessive daytime sleepiness. The genetic variations of the sleep patterns did not modify the relation between 25OHD and T2D. Our study indicates that higher serum 25OHD concentrations are associated with a lower risk of incident T2D, and such relations are modified by overall sleep patterns, with daytime sleepiness being the major contributor.

Screening of vitamin D and calcium concentrations in neonates of mothers at high risk of vitamin D deficiency

ObjectiveThe aim of this study was to determine, retrospectively, the serum 25OHD and calcium concentrations of screened neonates of mothers at high risk of 25OHD deficiency and examine whether their measurement contributes to the management of these neonates.MethodsSerum 25OHD and calcium concentrations from 600 samples of umbilical cord blood or venous blood collected from neonates over a 12-month period were analysed.ResultsThere was a high prevalence of vitamin D insufficiency (27.6%, 30–50 nmol/L) and deficiency (21.3%, < 30 nmol/L) in neonates from high-risk maternal groups. There was a statistically positive but weak correlation (ρ = 0.22, P < 0.0001) between 25OHD and serum calcium. Only 7 neonates out of 569 (1.2%) had calcium concentrations in the hypocalcaemic range; however, a significant number (47.6%) were reported to be in the hypercalcaemic range. Nearly all of these were venous samples collected in first 24 h after birth.ConclusionVitamin D deficiency is prevalent in neonates of high-risk mothers but the risk of hypocalcaemia due to vitamin D deficiency at birth is low. Screening neonates entails blood testing which can cause distress to neonates and their parents, substantial imposition on staff and financial burden on the health care system. Vitamin D supplementation of these neonates from birth without routine screening appears more reasonable. Also, the data from this study suggest that the paediatric reference range for corrected calcium concentrations in neonates should be re-evaluated.

Effects of source and level of in ovo-injected vitamin D3 on the hatchability and serum 25-hydroxycholecalciferol concentrations of Ross 708 broilers

Effects of the in ovo injection of vitamin D3 (D3) and 25-hydroxycholecalciferol (25OHD3) on broiler embryo serum 25OHD3 concentrations, hatchability, and hatchling somatic characteristics were determined. Eggs from a 35-wk-old commercial Ross 708 broiler breeder flock were set in a single-stage incubator with 11 treatments represented on each of 8 incubator tray levels (blocks). Each treatment group within a flat on each tray level contained 30 eggs. Control treatments were noninjected and diluent injected. Vitamin treatments were commercial diluent containing 0.6 μg D3, 0.6 μg 25OHD3, 0.6 μg D3 + 0.6 μg 25OHD3, 1.2 μg D3, 1.2 μg 25OHD3, 1.2 μg D3 + 1.2 μg 25OHD3, 2.4 μg D3, 2.4 μg 25OHD3, or 2.4 μg D3 + 2.4 μg 25OHD3. At 432 h of incubation (hoi), 50-μL solution volumes were injected. Blood samples were collected at 462 hoi for serum 25OHD3 analysis, and hatchability of injected live embryonated eggs (HI) was determined at 492 and 516 hoi. At 516 hoi, hatchling yolk-free BW and weights of the liver and yolk sac were determined. Percentage of yolk moisture and dry mater was calculated. At 492 and 516 hoi, HI did not differ between treatments. Embryos that received 1.2 μg or more of either vitamin D3 source alone or in combination had higher serum 25OHD3 concentrations than those that were injected with diluent alone or diluent containing 0.6 μg of D3. Hatchlings that received 1.2 or 2.4 μg of 25OHD3 had higher percentage of yolk dry matter or lower percentage of yolk moisture levels than noninjected controls and those that received D3 alone at any level. These results indicate that the in ovo injection of either vitamin D3 source at levels equal to or higher than 1.2 μg resulted in serum 25OHD3 concentrations that were higher than that of noninjected controls. In addition, the in ovo injection of 1.2 μg or higher of either vitamin D3 source did not negatively affect broiler HI or chick quality.

Effects of a single dose of vitamin D in septic children: a randomized, double-blinded, controlled trial.

ObjectiveTo assess the effects of a single dose of vitamin D on 25-hydroxyvitamin D (25OHD) levels and clinical outcomes in children with vitamin D deficiency (VDD) and sepsis.MethodsIn this randomized, controlled trial, eligible children with VDD and sepsis were assigned to receive one dose of 150,000 IU of cholecalciferol or placebo. Serum concentrations of 25OHD, angiotensin-II (Ang-II), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were assessed at baseline and 8 days after treatment. The cardiovascular Sequential Organ Failure Assessment (cv-SOFA) score, septic shock incidence, duration of ventilation, and mortality were also examined.ResultsOne hundred nine participants fulfilled the study requirements. The two groups had comparable baseline characteristics. Ang-II, IL-6, and TNF-α concentrations were all reduced after vitamin D supplementation. Furthermore, the cv-SOFA score (1.76 ± 0.8 vs. 2.3 ± 1.1) and incidence of septic shock (7% vs. 20%) were lower in the treatment group than in the control group. The duration of ventilation and mortality rates did not differ between two groups.ConclusionsA single dose of vitamin D improved 25OHD levels and the incidence of septic shock in children with VDD and sepsis.

Higher Serum Vitamin D Concentrations Are Longitudinally Associated with Better Global Quality of Life and Less Fatigue in Colorectal Cancer Survivors up to 2 Years after Treatment.

Vitamin D status may be an important determinant of health-related quality of life of colorectal cancer survivors. The current study investigated longitudinal associations between serum 25-hydroxyvitamin D3 (25OHD3) concentrations and quality of life in stage I-III colorectal cancer survivors up to 2 years after treatment. Patients with colorectal cancer (n = 261) were included upon diagnosis. Home visits (including blood sampling) were performed at diagnosis and at 6 weeks, 6 months, 1 year, and 2 years after treatment. Serum 25OHD3 concentrations were measured using LC/MS-MS and adjusted for season. Validated questionnaires were used to assess global quality of life and cognitive functioning (EORTC-QLQ-C30), fatigue (EORTC-QLQ-C30 and Checklist Individual Strength, CIS), and depression and anxiety (Hospital Anxiety and Depression Scale). Statistical analyses were performed using linear mixed models and adjusted for sex, age, time since diagnosis, therapy, comorbidities, physical activity, and body mass index. At diagnosis, 45% of patients were vitamin D deficient (<50 nmol/L). After treatment, 25OHD3 concentrations increased on average with 3.1 nmol/L every 6 months. In confounder-adjusted models, 20 nmol/L increments in 25OHD3 were longitudinally associated with increased global quality of life [β 2.9; 95% confidence interval (CI), 1.5-4.3] and reduced fatigue (EORTC-QLQ-C30 subscale: β -3.5; 95% CI, -5.3 to -1.8 and CIS: β -2.8; 95% CI, -4.7 to -0.9). Observed associations were present both within and between individuals over time. Higher concentrations of 25OHD3 were longitudinally associated with better global quality of life and less fatigue in colorectal cancer survivors. This study suggests that higher 25OHD3 concentrations may be beneficial for colorectal cancer survivors. Future intervention studies are needed to corroborate these findings.

SUN-083 Screening of Vitamin D and Calcium Concentrations in Neonates of Mothers at High Risk of Vitamin D Deficiency

Objective: The aim of this study was to determine, retrospectively, the serum 25OHD and calcium concentrations of screened neonates of mothers at high risk of 25OHD deficiency (maternal 25OHD < 25 nmol/L or unknown vitamin D concentrations and risk factors for vitamin D deficiency) and critically analyse whether their measurements contributes to the management of these neonates.Methods: Serum 25OHD and calcium concentrations from 600 samples of umbilical cord blood or venous blood collected from neonates over a 12-month period were analysed. 25OHD concentrations were reported for all while both the corrected calcium concentrations and vitamin D concentrations were available for 569 samples.Results: There was little or no evidence of association between neonatal 25OHD concentrations and gender, gestational age or birth weight. There was a high prevalence of vitamin D insufficiency (27.6%, 30–50 nmol/L) and deficiency (21.3%, < 30 nmol/L) in neonates from high-risk maternal groups. There was a statistically positive but weak correlation (ρ = 0.22, P < 0.0001) between serum calcium and 25OHD concentrations. Only 7 neonates out of 569 (1.2%) had calcium levels in the hypocalcaemic range; however, a significant number (47.6%) were reported to be in the hypercalcaemic range. Nearly all of these were venous samples collected in first 24 hours after birth. We calculated the reference interval for corrected calcium from our data of venous samples in first 24 hours and the upper limit was significantly higher (2.38–3.04 mmol/L) than the standard reference range used.Conclusion: Vitamin D deficiency is prevalent in neonates of high-risk mothers but the risk of hypocalcaemia due to vitamin D deficiency at birth is low. Screening neonates entails blood testing which can cause distress to neonates and their parents, substantial impost on staff and financial burden on the health care system. 25OHD deficiency is corrected relatively easily in neonates with supplementation and vitamin D supplementation of neonates from birth without routine screening appears to offer better value of care. Also, the data from this study suggest that the paediatric reference range for corrected calcium concentrations in neonates is higher and the paediatric reference range should be reconsidered.

Effects of Glycated Hemoglobin Level on Bone Metabolism Biomarkers in Patients with Type 2 Diabetes Mellitus.

PurposeWe aimed to determine the relationship between the levels of glycated hemoglobin (HbA1c) and biomarkers of bone metabolism in patients with type 2 diabetes mellitus (T2DM), and whether HbA1c independently influences any of these biomarkers.Patients and MethodsA cohort study of 240 patients with T2DM was performed. Serum was obtained and used to measure HbA1c, total cholesterol (TC), triglycerides, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol (LDL-C), very-low-density lipoprotein-cholesterol, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), total protein, albumin, blood urea nitrogen (BUN), creatinine, serum 25-hydroxyvitamin D (25OHD), osteocalcin (OC), β-C-terminal cross-linked telopeptide of type I collagen (β-CTX), procollagen type 1 N-terminal propeptide (P1NP), or parathyroid hormone (PTH) concentrations. The participants were divided into three study groups according to HbA1c level: <7%, 7–9% and ≥9%. Chi-square testing and one-way analysis of variance were used to compare groups. The relationships between HbA1c and bone metabolism biomarker values were analyzed using linear correlation analysis and multiple linear regression analysis.ResultsAge, duration of T2DM, and the concentrations of TC, LDL-C, apolipoprotein B, albumin, and BUN showed significant difference among the <7%, 7–9% and ≥9% HbA1c groups. Of the bone metabolism biomarkers, there were significant differences in serum 25-hydroxyvitamin D (25OHD) and osteocalcin (OC) among the groups. The correlation coefficients (r) for the relationships of HbA1c with 25OHD and OC were −0.200 and −0.183, respectively (P <0.05). Regardless of adjustment for none, some, or all of the confounding factors (age, sex, and duration of T2DM), the 25OHD and OC concentrations were significantly lower in the HbA1c ≥9% group than in the HbA1c <7% group. HbA1c showed no relationship with β-CTX, PINP, or PTH.ConclusionT2DM patients with poorer glycemic control had lower concentrations of serum 25OHD and OC, suggesting that HbA1c is an independent risk factor for low 25OHD and OC.

Vitamin D and fibroplastic processes in myocardium in spontaneously hypertensive rats with initial kidney dysfunction

Background. Even a moderate decrease in glomerular filtration rate leads to an increased risk of cardiovascular diseases (CVD), which is the leading cause of mortality in patients with chronic kidney disease (CKD). Left ventricular hypertrophy (LVH) underlies CVD development in renal dysfunction. The prevalence of LVH in patients with CKD stages 2–4 is 50–70 % and reaches 95 % at the beginning of dialysis, which significantly exceeds the number of cases in general population (15–21 %). Common hemodynamic factors associated with chronic kidney damage —hypertension (HTN), activation of the renin-angiotensin system, anemia, fluid and sodium retention, and others largely explain the high prevalence of LVH among patients with CKD. Nevertheless, the existence of additional non-hemodynamic mechanisms of myocardial remodeling (MR) is evident.Objective. To investigate the associations between the MR physiological/histological characteristics and laboratory parameters of calcium-phosphate metabolism in the initial stages of experimental CKD. Design and methods. Four groups of spontaneously hypertensive rats (SHR) were studied (n = 35): 3/4 nephrectomized rats (Nx) one month exposed after surgery (Nx(1), n = 9), 5/6 Nx two months after surgery (Nx(2), n = 8), sham operated rats one month after surgery (SO(1), n = 9) and two months after surgery (SO(2), n = 9). Myocardial mass index (MMI), systolic blood pressure (BP), proteinuria, creatinine (Cr) concentration, total calcium (Ca) and inorganic phosphate (Pi), 25-OH vitamin D (25OHD) and parathyroid hormone (PTH) in serum, myocardial morphology were studied in all experimental animals.Results. The models corresponded to the 1–3 stages CKD. There were no significant changes in serum total Ca (p = 0,066), Pi (p = 0,051) and PTH (p = 0,015) concentrations, the level of 25OHD was significantly lower in Nx(2) rats vs control (p = 0,015). MMI increased in all nephrectomized rats (p = 0,008). The cardiomyocytes (CM) thickness increased in Nx(1) and Nx(2) animals compared to the corresponding controls (p = 0,010, p = 0,002). A significant increase in interstitial (IF) and perivascular (PF) fibrosis occurred in Nx(2) rats with more damaging influence (p = 0,017, p = 0,004). CM thickness, IF and PF increased with the elevation of BP (r = 0,39, p = 0,038, r = 0,47, p = 0,026, r = 0,49, p = 0,031) and serum Cr (r = 0,68, p = 0,001, r = 0,61, p = 0,003, r = 0,69, p = 0,001), and the decrease in serum 25OHD concentration (r = –0,045, p = 0,047, r = –0,50, p = 0,020, r = –0,52, p = 0,012). Multiple linear regression analysis showed, that 25OHD is an independent predictor of myocardial fibrosis (IF: β = –0,38 ± 0,18, p = 0,047, PF: β = –0,34 ± 0,15, p = 0,032).Conclusions. The initial stages of CKD accompanied with HTN are associated with serum 25OHD concentration decrease CM hypertrophy and myocardial fibrosis. The CM growth is an earlier event in relation to the interstitial fibrosis. The obtained data suggest a possible role of vitamin D deficiency in the development of myocardial fibrotic lesions.

Low vitamin D levels predict left atrial thrombus in nonvalvular atrial fibrillation

Background and aimsWe determined the association between left atrial (LA) thrombus occurrence and a non-classic risk marker, plasma levels of vitamin D, in atrial fibrillation (AF) patients on continuous non-vitamin K antagonist oral anticoagulant (NOAC) therapy for ≥4 weeks. Low levels of plasma 25-hydroxy vitamin D (25-OHD) are predictive of fatal stroke. Vitamin D has anticoagulant effects on the coagulation cascade, which are indirectly targeted by NOAC therapy. The impact of plasma levels of vitamin D on the rate of LA thrombus detected by transesophageal echocardiography (TEE) in AF patients is unknown. Methods and resultsWe enrolled 201 (133 female) AF patients who were using continuous NOAC therapy for ≥4 weeks. All patients underwent transthoracic and TEE examination. Serum concentrations of 25-OHD, C-reactive protein (CRP) levels, CHA2DS2-VASc scores and parameters, LA size, and left ventricle ejection fraction (LVEF) were examined before the TEE procedure. LA thrombus occurrence was independently associated with serum levels of 25-OHD (OR: 0.884; 95% CI: 0.839–0.932; P < 0.001), LA diameter (OR: 1.120; 95% CI: 1.038–1.209; P = 0.003), and LVEF(OR: 0.944; 95% CI: 0.896–0.995; P = 0.032). Dense spontaneous echo contrast (SEC) presence was also inversely associated with 25-OHD concentrations. ConclusionsLow 25-OHD levels, as a non-classic risk factor, were independently and significantly associated with dense SEC and LA thrombus occurrence in AF patients under NOAC therapy, as well as LA enlargement and decreased LVEF. Further large-scale studies are needed to explain the role of vitamin D deficiency, or efficacy of replacement, on LA thrombus occurrence.

Combined Effect of Maternal Vitamin D Deficiency and Gestational Diabetes Mellitus on Trajectories of Ultrasound-Measured Fetal Growth: A Birth Cohort Study in Beijing, China.

Objective Few studies have examined whether maternal 25(OH)D deficiency and gestational diabetes mellitus (GDM) jointly affect fetal growth. We aimed to examine the separate and combined effects of maternal 25(OH)D deficiency and GDM on trajectories of fetal growth. Methods We established a birth cohort (2016-2017) with 10,913 singleton pregnancies in Tongzhou Maternal and Child Health Hospital of Beijing, China. Maternal 25(OH)D deficiency (serum 25(OH)D concentration < 20.0 ng/mL) was detected, and GDM was diagnosed at 24~28 gestational weeks. Fetal growth was assessed by longitudinal ultrasound measurements of estimated fetal weight (EFW) and abdominal circumference (AC) from 28 gestational weeks to delivery, both of which were standardized as gestational-age-adjusted Z-score. A k-means algorithm was used to cluster the longitudinal measurements (trajectories) of fetal growth. Logistic regression models were used for estimating exposure-outcome associations and additive interactions. Results We identified two distinct trajectories of fetal growth, and the faster one resembling the 90th centile curve in the reference population was classified as excessive fetal growth. Maternal 25(OH)D deficiency and GDM were independently associated with an increased risk of excessive fetal growth. The combination of maternal 25(OH)D deficiency and GDM was associated with an increased risk of excessive fetal growth assessed by EFW Z-score (odds ratio (OR): 1.36; 95% confidence interval (CI): 1.15~1.62) and AC Z-score (OR (95% CI): 1.32 (1.11~1.56)), but the relative excess risks attributable to interaction were nonsignificant (P > 0.05). Conclusion Maternal 25(OH)D deficiency and GDM may jointly increase the risk of excessive fetal growth. Interventions for pregnancies with GDM may be more beneficial for those with 25(OH)D deficiency than those without regarding risk of excessive fetal growth, if confirmed in a large sample.

Low serum 25-hydroxyvitamin D status in the pathogenesis of stress fractures in military personnel: An evidenced link to support injury risk management.

Stress fractures are common amongst healthy military recruits and athletes. Reduced vitamin D availability, measured by serum 25-hydroxyvitamin D (25OHD) status, has been associated with stress fracture risk during the 32-week Royal Marines (RM) training programme. A gene-environment interaction study was undertaken to explore this relationship to inform specific injury risk mitigation strategies. Fifty-one males who developed a stress fracture during RM training (n = 9 in weeks 1-15; n = 42 in weeks 16-32) and 141 uninjured controls were genotyped for the vitamin D receptor (VDR) FokI polymorphism. Serum 25OHD was measured at the start, middle and end (weeks 1, 15 and 32) of training. Serum 25OHD concentration increased in controls between weeks 1-15 (61.8±29.1 to 72.6±28.8 nmol/L, p = 0.01). Recruits who fractured did not show this rise and had lower week-15 25OHD concentration (p = 0.01). Higher week-15 25OHD concentration was associated with reduced stress fracture risk (adjusted OR 0.55[0.32-0.96] per 1SD increase, p = 0.04): the greater the increase in 25OHD, the greater the protective effect (p = 0.01). The f-allele was over-represented in fracture cases compared with controls (p<0.05). Baseline 25OHD status interacted with VDR genotype: a higher level was associated with reduced fracture risk in f-allele carriers (adjusted OR 0.39[0.17-0.91], p = 0.01). Improved 25OHD status between weeks 1-15 had a greater protective effect in FF genotype individuals (adjusted OR 0.31[0.12-0.81] vs. 1.78[0.90-3.49], p<0.01). Stress fracture risk in RM recruits is impacted by the interaction of VDR genotype with vitamin D status. This further supports the role of low serum vitamin D concentrations in causing stress fractures, and hence prophylactic vitamin D supplementation as an injury risk mitigation strategy.

Vitamin D concentration and focal brain atrophy in older adults: a voxel-based morphometric study.

Vitamin D is involved in brain health and function. Our objective was to determine whether lower 25‐hydroxyvitamin D (25OHD) concentration was associated with focal brain volume reduction in older adults. Serum 25OHD concentration was measured among 53 older adults (72 ± 5 years; 38% female; mean 25OHD = 67.3 ± 20.8 nmol/L). Gray matter volume (GMV) was automatically segmented using voxel‐based morphometry with CAT12 software. Covariables were age, gender, education, total intracranial volume, and season. Serum 25OHD was positively associated with GMV in left calcarine sulcus (P < 0.05, TFCE, FWE‐corrected). We found atrophy of the calcarine sulcus with lower 25OHD concentrations in older adults.

Effect of Intravenous 25OHD Supplementation on Bone Turnover and Inflammation in Prolonged Critically Ill Patients.

Critically ill patients have low circulating 25-hydroxyvitamin D (25OHD), vitamin D binding protein (DBP), and 1,25-dihydroxyvitamin D [1,25(OH)2D]. Low 25OHD is associated with poor outcomes, possibly explained by its effect on bone and immunity. In this prospective, randomized double-blind, placebo-controlled study, we investigated the feasibility of normalizing 25OHD in prolonged (>10 days) critically ill patients and the effects thereof on 1,25(OH)2D, bone metabolism, and innate immunity. Twenty-four patients were included and compared with 24 matched healthy subjects. Patients were randomized to either intravenous bolus of 200 μg 25OHD followed by daily infusion of 15 μg 25OHD for 10 days, or to placebo. Parameters of vitamin D, bone and mineral metabolism, and innate immune function were measured. As safety endpoints, ICU length of stay and mortality were registered. Infusion of 25OHD resulted in a sustained increase of serum 25OHD (from median baseline 9.2 -16.1 ng/ml at day 10), which, however, remained below normal levels. There was no increase in serum 1,25(OH)2D but a slight increase in serum 24,25(OH)2D. Mineral homeostasis, innate immunity and clinical safety endpoints were unaffected. Thus, intravenous 25OHD administration during critical illness increased serum 25OHD concentrations, though less than expected from data in healthy subjects, which suggests illness-induced alterations in 25OHD metabolism and/or increased 25OHD distribution volume. The increased serum 25OHD concentrations were not followed by a rise in 1,25(OH)2D nor were bone metabolism or innate immunity affected, which suggests that low 25OHD and 1,25OHD levels are part of the adaptive response to critical illness.

Serum 25 hydroxyvitamin D status in 6-month-old infants in Guangzhou, China: A paired longitudinal follow up study.

To assess the vitamin D status in healthy 6‐month‐old infants, as well as vitamin D supplementation and feeding patterns in Guangzhou, China, serum 25‐hydroxyvitamin D (25OHD) concentrations of 202 infants were measured at birth (cord blood) and at 6 months of age in Guangzhou, China. Questionnaires acquiring demographic characteristics, maternal and infantile vitamin D supplementation during pregnancy and first 6 months after birth, and feeding patterns during the first 6 months were completed by participating mothers. Physical examinations and blood sampling were carried out among infants at 6 months of age. The majority of infants (93.6%) were supplemented with vitamin D during the first 6 months of life on a voluntary basis. The M ± SD of cord serum 25OHD concentration was 46.2 ± 16.4 nmol/L, whereas the M ± SD of 25OHD concentration at 6 months was 82.9 ± 24.9 nmol/L. Serum 25OHD concentrations <30 nmol/L were seen in 34 (16.8%) infants at birth but only one (0.5%) at 6 months. Only 11 (5.4%) infants had concentrations >75 nmol/L at birth, whereas the majority of infants (n = 131, 64.9%) had concentrations >75 nmol/L at 6 months. The main predictors of 25OHD levels at 6 months included season, vitamin D supplementation, parental education level, and feeding patterns. To conclude, serum 25OHD concentrations were low at birth in a southern Chinese population, and infantile supplementation is an effective way to improve 25OHD status. Exclusively breastfed infants might need greater vitamin D supplementation, and individualized vitamin D supplementation plans might be needed.

Canadian recommendations for vitamin D intake for persons affected by multiple sclerosis

In 2016, the Multiple Sclerosis (MS) Society of Canada convened a panel of expert scientists, clinicians and patient advocate to review the evidence for an association between vitamin D status and MS prevention and/or disease modification. The goal was to develop clear and accurate recommendations on optimal vitamin D intake and status for people affected by MS for use in clinical practice and public health policy. The final consensus report was based on a review and grading of existing published papers combined with expert opinions of panel members. The report led to recommendations published in November of 2018 on the website of the MS Society of Canada, one in a format for use by health professionals and another in a question and answer format that was targeted to persons affected by MS and the general public. For people at risk of developing MS, the vitamin D recommendations are similar to those for the general public following the Dietary Reference Intakes (DRI) for Canada and the United States. Adults should achieve and maintain a normal vitamin D status with monitoring by physicians (serum 25-hydroxyvitamin D (25(OH)D) = 50−125 nmol/L, requiring 600–4000 IU vitamin D/d intake). For pregnant women, newborn infants, and all youth at risk of MS, vitamin D intakes should also follow DRI recommendations but additionally their serum 25-(OH)D should be monitored. For persons living with MS, existing evidence did not allow prediction of a vitamin D intake that might modify MS disease course. For this group the recommendations included: (1) serum 25-(OH)D should be maintained in the range of 50–125 nmol/L (600–4000 IU/d intake).; and (2) vitamin D should not be used as a standalone treatment for MS. For children and adolescents, serum 25OHD status was recommended to be measured upon diagnosis of a first clinical demyelinating event, and monitored every 6 months to achieve a target of 75 nmol/L Since people living with MS are at increased risk of osteoporosis, falls, and bone fractures, it was recommended to achieve a minimum serum 25OHD concentration that is protective for bone health in the general population. The revision of the MS Society recommendations on vitamin D awaits future clinical trial evidence.

Serum 25-hydroxyvitamin D concentration in childhood and risk of islet autoimmunity and type 1 diabetes: the TRIGR nested case\u2013control ancillary study

Aims/hypothesisOur aim was to study the association between serum 25-hydroxyvitamin D (25OHD) concentration and islet autoimmunity and type 1 diabetes in children with an increased genetic risk of type 1 diabetes.MethodsSerum samples for 25OHD measurements were obtained in the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) ancillary study (Divia) from children in 15 countries. Case children (n = 244) were defined as having positivity for at least two out of four diabetes-associated autoantibodies measured at any one sample. For each case child, two control children were selected matched for country and date of birth (±1 year) (n = 488). Of the case children, 144 developed type 1 diabetes. Serum 25OHD was measured repeatedly in infancy and childhood and was compared according to age at the first seroconversion (at 6, 12 and 18 months prior to and at seroconversion) and calendar age (0, 6, 12 and 18 months).ResultsIn children with islet autoimmunity, mean serum 25OHD concentration was lower 18 months prior to the age of first seroconversion of the case children compared with the control children (57.7 vs 64.8 nmol/l, p = 0.007). In children with type 1 diabetes (n = 144), mean serum 25OHD concentration was lower 18 months prior to the age of the first seroconversion (58.0 vs 65.0 nmol/l, p = 0.018) and at the calendar age of 12 months (70.1 vs 75.9 nmol/l, p = 0.031) than in their control counterparts. Analyses were adjusted for month of sample collection, human leucocyte antigen genotype, maternal type 1 diabetes and sex.Conclusions/interpretationThe results suggest that early postnatal vitamin D may confer protection against the development of type 1 diabetes.Trial registrationClinicalTrials.gov NCT00179777

Comparative effectiveness of vitamin D supplementation via buccal spray versus oral supplements on 25(OH)D concentrations: a systematic review

AbstractVitamin D (vitD) deficiency is the most common nutritional deficiency worldwide. Most patients are treated with oral vitD capsules (either vitD2 or vitD3). A few studies have reported equal efficacy of buccal spray vitD. This is a new formulation that is absorbed via the oral mucosa into the systemic circulation, bypassing the gastrointestinal route. The main objective of this systematic review was to identify RCT evidence for the comparative effectiveness of buccal spray versus oral vitD on serum 25-hydroxyvitaminD [25-OHD] concentrations and any adverse effects of buccal spray vitD. We have published an a priori protocol using Joanna Briggs Institute (JBI) methodology (PROSPERO CRD42018118580). A three-step search strategy to identify RCTs was conducted, which reported serum 25-OHD concentrations from five databases from 2008–2018. Retrieved abstracts were screened; included papers imported into JBI SUMARI and assessed for study quality (GRADE) by two authors. Meta-analysis was planned. Three RCTs met our inclusion criteria. Due to heterogeneity of studies, meta-analysis was not possible. In a RCT crossover study, mean serum 25-OHD concentrations were significantly higher in patients with malabsorption syndrome (n = 20) on 1000IU buccal spray + 117.8%(10.46, 95%CI6.89,14.03ng/ml) vs.1000IU oral vitD3 + 36.02%(3.96, 95%CI2.37, 5.56ng/ml) at 30days (p &lt; 0.0001). Mean serum 25-OHD were also significantly higher in healthy adults (n = 20) on buccal spray + 42.99%(7.995, 95%CI6.86,9.13ng/ml)vs.oral vitD3 + 21.72%(4.06, 95%CI3.41,4.71ng/ml) at 30days (p &lt; 0.0001). In another RCT crossover study, ANCOVA revealed no significant difference in the mean and SD change from baseline total 25-OHD concentrations in adults (n = 22) on 3000IU buccal spray vs. 3000IU oral vitD3 + 44%,26.15 (SD17.85) vs. + 51%,30.38 (SD17.91)nmol/l, respectively;F = 1.044, adjusted r20.493,p = 0.313 at 4 weeks. In a RCT, 800IU buccal spray was equally effective as 750IU oral vitD3 in children with neurodisabilities(n = 24) at 3 months. Both groups had a significant increase in 25-OHD; 11.5 ng/ml(median8–19) to 26.5(13.6–39)ng/ml and 15.5ng/ml(8–20) to 34.5(22–49)ng/ml, respectively (z = 150;p &lt; 0.0001). The overall certainty of evidence was very low to moderate. No adverse effects were reported. The evidence from these studies suggests that 800IU-3000IU doses of buccal spray vitD3 given daily may be an effective alternative as oral vitD3 in obtaining short-term haematological responses in serum 25-OHD concentrations. Buccal spray vitD3 may be a useful alternative for patients with intestinal malabsorption or dysphagia. Future research should compare buccal spray VD3 to intramuscular injections and confirm these findings in well-designed trials.