Impact of Periconceptional and Gestational Vitamin D3 Restriction on Fetal Folliculogenesis and Anti-Mullerian Hormone Secretion Using Sheep as a Model.

Ovarian reserve is a reflection of the overall female reproductive potential. Vitamin D status has been suspected to influence fetal development and female fertility. As maternal diet during pregnancy can affect fetal development and future fertility, we hypothesised that periconceptional and gestational Vitamin D restriction could affect folliculogenesis and AMH secretion in the offspring. Nineteen sexually mature Welsh mountain ewes were randomly assigned to Vitamin D3 deficient (VDD, n = 10) and Vitamin D3 control (VDC, n = 9) diets from 17 days (d) before mating, up to 127-130 days of gestation, when fetal ovaries were collected (3 from VDC and 6 from VDD). Serum 25(OH)D3 concentrations were lower in VDD compared with VDC (p < 0.05). Relative to total follicle number, the percentage of primordial follicles was higher (p < 0.05), while the percentage of primary follicles was lower (p < 0.05) in VDD group compared with VDC group fetal ovaries. The integrated density value and percentage of affected area in TUNEL staining in VDD group did not vary from VDC group fetal ovaries (p > 0.05). Relative expression of AMH mRNA and AMH protein in VDD fetal ovaries were not statistically different compared with controls (p > 0.05). The relative expression of VDR mRNA were lower in VDD compared with VDC group fetal ovaries (p < 0.05). These data indicate that maternal Vitamin D dietary restriction is associated with ovarian tissue stemness and increased primordial follicle number but does not promote normal follicle recruitment or development in sheep fetal ovaries.

Sedentary behaviour and bone health in older adults: a systematic review.

Older adults spend more than 8 h/day in sedentary behaviours. Detrimental effects of sedentary behaviour (SB) on health are established, yet little is known about SB and bone health (bone mineral density; BMD) in older adults. The purpose of this review is to examine associations of SB with BMD in older adults. Five electronic databases were searched: Web of Science (Core Collection); PubMed; EMBASE; Sports Medicine and Education and PsycInfo. Inclusion criteria were healthy older adults mean age ≥ 65 years; measured SB and measured BMD using dual-energy X-ray absorptiometry. Quality was assessed using National Institute of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. After excluding duplicates 17813 papers were assessed; 17757 were excluded on title/abstract, 49 at full text, resulting in two prospective and five cross-sectional observational studies reviewed. Four were rated 'good' and three were rated 'fair' using the quality assessment criteria. Findings varied across the studies and differed by gender. In women, four studies reported significant positive associations of SB with BMD at different sites, and two found significant negative associations. Five studies which examined both men and women, men reported negative or no associations of SB with femoral neck, pelvic, whole body, spine or leg BMD. Whilst these findings suggest differences between men and women in the associations of SB with BMD, they may be due to the varying anatomical sections examined for BMD, the different methods used to measure SB, the varied quality of the studies included and the limited number of published findings.

Longevity of daily oral vitamin D3 supplementation: differences in 25OHD and 24,25(OH)2D observed 2 years after cessation of a 1-year randomised controlled trial (VICtORy RECALL).

To determine how long vitamin D lasts after supplementation ceases, the marker of status was measured 2 and 3 years after a 1-year trial. Compared to placebo, the proportion of vitamin D-deficient women was still lower, if they had taken daily vitamin D3, after 2 years, indicating its longevity. INTRODUCTION: The purpose of this study was to determine longevity of vitamin D status following cessation of vitamin D3 supplementation, 2 and 3 years after a 1-year randomised, double-blind placebo controlled trial and to investigate possible predictive factors. METHODS: Caucasian non-smoking postmenopausal women randomised to ViCtORY (2009-2010), who had not taken vitamin D supplements since the trial ended, were invited to attend follow-up visits. Total 25-hydroxyvitamin D (25OHD) and 24,25-dihydroxyvitamin D (24,25OH2D) were measured by dual tandem mass spectrometry of serum samples following removal of protein and de-lipidation; the original randomised controlled trial (RCT) samples were re-analysed simultaneously. Vitamin D-binding protein (VDBP) was measured by monoclonal immunoassay. RESULTS: In March 2012 and March 2013, 159 women (mean (SD) age 67.6 (2.1) years) re-attended, equally distributed between the original treatment groups: daily vitamin D3 (400 IU, 1000 IU) and placebo. One month after the RCT ended (March 2010), the proportion of women in placebo, 400 IU and 1000 IU vitamin D3 groups, respectively, with 25OHD < 25 nmol/L was 15, 0 and 0 (chi-square p < 0.001, n = 46, 44, 54). After 2 years (March 2012), it was 22, 4 and 4% (p = 0.002, n = 50, 48, 57); after 3 years, it was 23, 13 and 15% (p = 0.429, n = 48, 45, 52). The respective proportions of women with 24,25OH2D < 2.2 nmol/L were 50, 2 and 2% (1 month, p < 0.001, n = 46, 44, 54); 42, 33 and 12% (2 years, p = 0.002, n = 50, 48, 57); and 45, 27 and 29% (3 years, p = 0.138, n = 47, 45, 51). VDBP was a predictor of circulating 25OHD longevity (beta for VDBP in µg/mL 0.736; 95% CI 0.216-1.255, p = 0.006) but not 24,25OH2D. CONCLUSION: Four hundred international units or 1000 IU of daily vitamin D3 showed benefits over placebo 2 years after supplementation ceased in keeping 25OHD > 25 nmol/L.

Prevalence, incidence and determinants of QuantiFERONTM positivity in South African schoolchildren.

BACKGROUND: TB control requires the understanding and disruption of TB transmission. We describe prevalence, incidence and risk factors associated with childhood TB infection in Cape Town, South Africa. METHODS: We report cross-sectional baseline and prospective incidence data from a large trial among primary school children living in high TB burden communities. Prevalent infection was defined as QuantiFERON™-TB Gold Plus (QFT-Plus) positivity as assessed at baseline. Subsequent conversion to QFT-Plus positivity was measured 3 years later among those QFT-Plus-negative at baseline. Multivariable logistic regression models examined factors associated with TB infection. RESULTS: QuantiFERON-positivity at baseline (prevalence: 22.6%, 95% CI 20.9-24.4), was independently associated with increasing age (aOR 1.24 per additional year, 95% CI 1.15-1.34) and household exposure to TB during the participant's lifetime (aOR 1.87, 95% CI 1.46-2.40). QFT-Plus conversion at year 3 (12.2%, 95% CI 10.5-14.0; annual infection rate: 3.95%) was associated with household exposure to an index TB case (aOR 2.74, 95% CI 1.05-7.18). CONCLUSION: Rates of QFT-diagnosed TB infection remain high in this population. The strong association with household TB exposure reinforces the importance of contact tracing, preventative treatment and early treatment of infectious disease to reduce community transmission.

CONTEXTE: La lutte contre la TB nécessite la compréhension et la perturbation de la transmission de la TB. Nous décrivons la prévalence, l'incidence et les facteurs de risque associés à l'infection tuberculeuse infantile au Cap, en Afrique du Sud. MÉTHODES: Nous rapportons des données transversales de référence et d'incidence prospective provenant d'un vaste essai mené auprès d'enfants d'écoles primaires vivant dans des communautés à forte charge de morbidité tuberculeuse. La prévalence de l'infection a été définie comme la positivité au QuantiFERON™-TB Gold Plus (QFT-Plus) telle qu'évaluée au départ. La conversion subséquente en QFT-Plus positif a été mesurée 3 ans plus tard chez les QFT-Plus négatifs au départ. Des modèles de régression logistique multivariée ont examiné les facteurs associés à l'infection tuberculeuse. RÉSULTATS: La positivité QuantiFERON-au départ (prévalence : 22,6%, IC à 95% 20,9­24,4), était indépendamment associée à l'augmentation de l'âge (aOR 1,24 par année supplémentaire, IC à 95% 1,15­1,34) et à l'exposition du ménage à la TB au cours de la vie du participant (aOR 1,87 ; IC à 95% 1,46­2,40). La conversion QFT-Plus à l'année 3 (12,2%, IC à 95% 10,5­14,0 ; taux d'infection annuel : 3,95%) était associée à l'exposition du ménage à un cas de tuberculose index (aOR 2,74 ; IC à 95% 1,05­7,18). CONCLUSION: Les taux d'infection tuberculeuse diagnostiquée par QFT restent élevés dans cette population. La forte association avec l'exposition à la TB dans les ménages renforce l'importance de la recherche des contacts, du traitement préventif et du traitement précoce des maladies infectieuses pour réduire la transmission communautaire.

Hormonal contraceptive use, bone density and biochemical markers of bone metabolism in British Army recruits.

INTRODUCTION: Hormonal contraceptive use might impair bone health and increase the risk of stress fracture by decreasing endogenous oestrogen production, a central regulator of bone metabolism. This cross-sectional study investigated bone density and biochemical markers of bone metabolism in women taking hormonal contraceptives on entry to basic military training. METHODS: Forty-five female British Army recruits had biochemical markers of bone metabolism, areal bone mineral density (aBMD) and tibial speed of sound (tSOS) measured at the start of basic military training. Participants were compared by their method of hormonal contraception: no hormonal contraception (NONE), combined contraceptive pill (CP) or depot-medroxyprogesterone acetate (DMPA) (20±2.8 years, 1.64±0.63 m, 61.7±6.2 kg). RESULTS: aBMD was not different between groups (p≥0.204), but tSOS was higher in NONE (3%, p=0.014) when compared with DMPA users. Beta C-terminal telopeptide was higher in NONE (45%, p=0.037) and DMPA users (90%, p=0.003) compared with CP users. Procollagen type 1 N-terminal propeptide was higher in DMPA users compared with NONE (43%, p=0.045) and CP users (127%, p=0.001), and higher in NONE compared with CP users (59%, p=0.014). Bone alkaline phosphatase was higher in DMPA users compared with CP users (56%, p=0.044). CONCLUSIONS: DMPA use was associated with increased bone turnover and decreased cortical bone integrity of the tibia. Lower cortical bone integrity in DMPA users was possibly mediated by increased intracortical remodelling, but trabecular bone was not affected by contraceptive use.

The effects of short-term low energy availability, achieved through diet or exercise, on cognitive function in oral contraceptive users and eumenorrheic women.

To date, no research has explored the effects of low energy availability on cognitive performance using dietary and exercise regimens relevant to athletes. Twenty female participants (10 eumenorrheic, 10 oral contraceptive [OC] users) completed three 3-day conditions: 1) controlled-balanced energy availability without exercise (BAL; 45 kcal·kg lean body mass [LBM]-1·day-1); 2) diet-induced low energy availability without exercise (DIET; 15 kcal·kg LBM-1·day-1); and 3) exercise-induced low energy availability (EX; 15 kcal·kg LBM-1·day-1, including 30 kcal·kg LBM-1·day-1 treadmill running at 70% maximal oxygen uptake). A cognitive test battery was completed before and after each 3-day condition. Mental rotation test accuracy improved in the BAL condition, but there was a decline in accuracy in the EX condition (BAL, +2.5%; EX, -1.4%; P = 0.042, d = 0.85). DIET (+1.3%) was not different to BAL or EX (P > 0.05). All other measures of cognitive performance were not affected by condition (P > 0.05) and OC use did not affect cognitive responses (P > 0.05). Accuracy in the mental rotation test was impaired when low energy availability was induced through increased exercise energy expenditure. All other aspects of cognition were unaffected by 3 days of low energy availability through diet or exercise. OC use did not mediate the effect of low energy availability on cognition. Novelty: Cognitive function was not affected by 3 days of diet-induced low energy availability. Only spatial awareness was impaired during 3 days of exercise-induced low energy availability. Reproductive hormones affected spatial awareness independent of energy availability.

Gestational hypercalcemia: Prevalence and biochemical profile.

Gestational hypercalcemia is associated with an increased risk of maternal, fetal and neonatal morbidity and mortality. Hypercalcemia may develop during pregnancy in individuals who were previously asymptomatic. The increased sensitivity during pregnancy may be related to physiological, gestational alterations in vitamin D and calcium metabolism and may be influenced by gene variants. The prevalence is unknown. We investigated the prevalence of hypercalcemia in trimester 3 (T3) in a population representative prospective cohort study (n = 1832) in South-West Sweden. Women with serum albumin (Alb) adjusted calcium (CaAlb) ≥ 2.65 mmol/L in T3 (n = 30) were matched to normo-calcemic controls, and markers of calcium and vitamin D metabolism were investigated in trimester 1 (T1) and T3. Serum concentrations of Ca, phosphate (P), Magnesium (Mg), Alb and creatinine (Cr), parathyroid hormone (PTH; T3 only), vitamin D metabolites (total 25(OH)D, 1,25(OH)2D, 24,25(OH)2D, and free 25(OH)D) were analysed in T1 and T3. CaAlb (Payne; inter-laboratory difference: UEA = 0.15 + 0.9*UGOT; UEA 2.54 = UGOT 2.65) and estimated glomerular filtration rate (eGFR; modified 4-variable MDRD) and vitamin D metabolites ratios (VMR) were calculated. Normally and non-normally distributed data were presented as mean (SD) or median (95 %CI). Group differences in relationships between vitamin D metabolites and with PTH were investigated with multiple regression analyses. Hypercalcemia in T3 was found in 1.7 % of women. PTH concentrations suggestive of primary hyperparathyroidism was found in 1 woman and none had 25(OH)D or 24,25(OH)2D concentrations in the toxicity range or suggestive of mutations in the CYP24A1 gene. CaAlb was significantly higher in hypercalcemic cases compared to controls in T1 (2.44 (2.30-2.80) vs 2.37 (2.25-2.49) mmol/L) and T3 (2.63 (2.52-2.78) vs 2.46 (2.31-2.58) mmol/L). Serum P was higher among cases than controls in T3 (1.12 (0.16) vs 1.07 (0.18) mmol/L) but not in T1 (1.12 (0.18) and 1.12 (0.16) mmol/L). PTH in T3 was lower in cases (1.6 (1.6-2.8) vs 2.3 (2.1-2.8) pmol/L) but 1,25(OH)2D concentrations were similar. There were no significant group differences in serum 25(OH)D, free 25(OH)D, 24,25(OH)2D, Mg, Alb, Cr and eGFR. Regression analyses did not show significant differences between cases and controls in relationships between vitamin D metabolites and with PTH, except for the free 25(OH)D-PTH relationship and a higher free:total 25(OH)D ratio in cases at T1. In conclusion, most common causes of hypercalcemia were excluded in the majority of women. Hypercalcemic women had a relatively high serum 1,25(OH)2D concentration despite an appropriately suppressed PTH, suggestive of abnormal gestational adaptions.

Reduced fetal vitamin D status by maternal undernutrition during discrete gestational windows in sheep.

Placental transport of vitamin D and other nutrients (e.g. amino acids, fats and glucose) to the fetus is sensitive to maternal and fetal nutritional cues. We studied the effect of maternal calorific restriction on fetal vitamin D status and the placental expression of genes for nutrient transport [aromatic T-type amino acid transporter-1 (TAT-1); triglyceride hydrolase/lipoprotein uptake facilitator lipoprotein lipase (LPL)] and vitamin D homeostasis [CYP27B1; vitamin D receptor (VDR)], and their association with markers of fetal cardiovascular function and skeletal muscle growth. Pregnant sheep received 100% total metabolizable energy (ME) requirements (control), 40% total ME requirements peri-implantation [PI40, 1-31 days of gestation (dGA)] or 50% total ME requirements in late gestation (L, 104-127 dGA). Fetal, but not maternal, plasma 25-hydroxy-vitamin D (25OHD) concentration was lower in PI40 and L maternal undernutrition groups (P<0.01) compared with the control group at 0.86 gestation. PI40 group placental CYP27B1 messenger RNA (mRNA) levels were increased (P<0.05) compared with the control group. Across all groups, higher fetal plasma 25OHD concentration was associated with higher skeletal muscle myofibre and capillary density (P<0.05). In the placenta, higher VDR mRNA levels were associated with higher TAT-1 (P<0.05) and LPL (P<0.01) mRNA levels. In the PI40 maternal undernutrition group only, reduced fetal plasma 25OHD concentration may be mediated in part by altered placental CYP27B1. The association between placental mRNA levels of VDR and nutrient transport genes suggests a way in which the placenta may integrate nutritional cues in the face of maternal dietary challenges and alter fetal physiology.