cholecalciferol and Pre-Eclampsia

Vitamin D has historically been considered to play a role solely in bone and calcium metabolism. Human disease associations and basic physiological studies suggest that vitamin D deficiency is plausibly implicated in adverse health outcomes including mortality, malignancy, cardiovascular disease, immune functioning and glucose metabolism. There is considerable evidence that low maternal levels of 25 hydroxyvitamin D are associated with adverse outcomes for both mother and fetus in pregnancy as well as the neonate and child. Vitamin D deficiency during pregnancy has been linked with a number of maternal problems including infertility, preeclampsia, gestational diabetes and an increased rate of caesarean section. Likewise, for the child, there is an association with small size, impaired growth and skeletal problems in infancy, neonatal hypocalcaemia and seizures, and an increased risk of HIV transmission. Other childhood disease associations include type 1 diabetes and effects on immune tolerance. The optimal concentration of 25 hydroxyvitamin D is unknown and compounded by difficulties in defining the normal range. Whilst there is suggestive physiological evidence to support a causal role for many of the associations, whether vitamin D deficiency is a marker of poor health or the underlying aetiological problem is unclear. Randomised controlled trials of vitamin D supplementation with an appropriate assessment of a variety of health outcomes are required.

Topics: Cholecalciferol; Diabetes Mellitus; Diabetes, Gestational; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Lactation; Muscle, Skeletal; Parathyroid Hormone; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Reference Values; Skin; Vitamin D Deficiency

Vitamin D plays an important role in the release of the placenta and implantation, and low levels are a risk factor for pre-eclampsia. Studies have also shown that symptomatic treatment of vitamin D3 deficiency can effectively reduce the risk of pre-eclampsia. In this study, vitamin D3 supplementation was performed on the risk of pre-eclampsia to observe its effect.. From January 2016 to December 2018, 450 women with maternal treatment and delivery in our hospital underwent an open-label randomized study. The pregnant women were divided into low-dose, medium-dose, and high-dose groups. Compare the incidence of pre-eclampsia and the dose effect of vitamin D levels.. In the maternal and perinatal periods of the 450 maternal women, the 25[OH] index of the three groups of pregnant women was significantly increased, while the high-dose increase index was more obvious. The relative risk reduction rate was significantly lower. Compared with the low-dose and middle-dose groups, the high-dose group had a significantly lower incidence of pre-eclampsia, while the IUGR index was lower, and other obstetric indicators were comparable.. Vitamin D supplementation can effectively reduce the incidence of pre-eclampsia, while reducing the IUGR index, which has important value and significance in its clinical application.

Topics: Adult; Cholecalciferol; Dietary Supplements; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Incidence; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Risk Assessment; Risk Factors; Vitamin D Deficiency; Vitamins

Vitamin D plays pivotal role in decidualization and implantation of the placenta. Recent researches have shown that low level of vitamin D3 "25-hydroxyvitamin D (25[OH]D)" in serum is a risk factor for pre-eclampsia. Latest evidence supports role of vitamin D3 deficiency treatment in reducing the risk of pre-eclampsia. The aim of this study is to determine the effect of antenatal supplementation of vitamin D3 on the risk of pre-eclampsia and to explore the dose effect in attaining the vitamin D3 normal level.. An open labelled randomized controlled study was conducted on 179 pregnant women presenting in King Fahad Medical City antenatal clinic from Oct 2012-Oct 2015. Patients with age less than 20 years or more than 40 years, pregnancy with fetal anomalies, history of hypertension, pre-eclampsia, recurrent miscarriage, chronic renal or hepatic disease and malignancy were excluded from the study. Serum 25[OH]D was analysed during the first trimester (between 6 and 12 weeks of pregnancy). Patients with vitamin D3 deficiency (serum levels <25 nmol/L) were included in the study and randomized for vitamin D3 supplementation 400 IU (Group 1) versus 4000 IU (Group 2). Both groups were compared for the prevalence of pre-eclampsia and dose effect on vitamin D level.. Of 179 gravidae enrolled, 164 completed the trial. Mean maternal 25[OH]D was significantly increased in group 2 from 16.3 ± 5 nmol/mL to 72.3 ± 30.9 nmol/mL compared with group 1 from 17.5 ± 6.7 nmol/mL to 35.3 ± 20.7 nmol/mL (p > 0.0001). The relative risk reduction (RRR) for attaining ≥75 nmol/L before delivery was significantly higher (RRR 93.2 [CI 79-98] when treated with 4000 IU. The total incidence of pre-eclampsia in the study population was 4.3%. In comparison to group 1, the group 2 reported fewer pre-eclampsia events during the study period (8.6% versus 1.2%; p < 0.05). The total number of IUGRs was lesser in the group 2 (9.6%) versus group 1 (22.2%); p = 0.027. However, other obstetric outcomes were comparable between both groups.. Vitamin D supplementation in the deficient group reduces the risk of pre-eclampsia and IUGR in a dose dependant manner. However larger clinical trials are essential to investigate optimum dosage of vitamin D3 in this group.

Topics: Adult; Cholecalciferol; Dietary Supplements; Female; Humans; Pre-Eclampsia; Pregnancy; Risk; Vitamins; Young Adult

Soluble FMS-like tyrosine kinase 1 (sFlt-1) and vascular endothelial growth factor (VEGF) gene expression was significantly downregulated in the maternal subgroup with circulating 25(OH)D ≥100ng/mL compared to the subgroup <100ng/mL.. Here, we report a significant association between maternal vitamin D status and the expression of sFlt-1 and VEGF at the mRNA level. Achieving maternal circulating 25(OH)D ≥100nmoles/L suggests the impact of maternal vitamin D

Topics: Adult; Biomarkers; Cholecalciferol; Comorbidity; Down-Regulation; Female; Humans; Placenta; Pre-Eclampsia; Pregnancy; RNA, Messenger; Transcriptional Activation; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vitamin D; Vitamin D Deficiency; Vitamins; Young Adult

The present study was designed to examine the effects of vitamin D plus calcium administration on metabolic profiles and pregnancy outcomes among women at risk for pre-eclampsia.. In a prospective, double-blind, placebo-controlled trial, 60 women at risk for pre-eclampsia were randomised to take either 50 000 IU vitamin D3 every 2 weeks plus 1000 mg day(-1) calcium supplements (as calcium carbonate) (n = 30) or to receive placebos at the same times (n = 30) from 20 to 32 weeks of gestation. Fasting blood samples were taken at baseline and 12 weeks after intervention to determine related variables. Newborn anthropometric measurements were determined.. Taking combined cholecalciferol and calcium supplements, compared to placebo, led to significant reductions in fasting plasma glucose (FPG) [mean (SD)] [-5.7 (5.5) versus -0.6 (12.6) mg dL(-1) , P = 0.04], serum insulin concentrations [-2.8 (6.0) versus +7.7 (9.8) μIU mL(-1) , P < 0.001], homeostasis model of assessment-insulin resistance [-0.8 (1.3) versus +1.6 (2.2), P < 0.001], homeostatic model assessment-beta cell function [-8.2 (25.8) versus +32.6 (41.3, P < 0.001] and a significant rise in quantitative insulin sensitivity check index score [+0.02 (0.02) versus -0.02 (0.02, P < 0.001]. Additionally, pregnant women who received cholecalciferol plus calcium supplements had increased serum high-density lipoprotein (HDL)-cholesterol [+4.6 (8.3) versus -2.9 (7.7) mg dL(-1) , P = 0.001] and plasma total glutathione (GSH) concentrations [+23.4 (124.0) versus -94.8 (130.2) μm, P = 0.001] compared to placebo. However, after adjustment for the baseline levels, maternal age and baseline body mass index, the effects on FPG levels (P = 0.13) and systolic blood pressure (P = 0.13) disappeared.. Vitamin D plus calcium administration for 12 weeks had beneficial effects on glycaemic status, HDL-cholesterol, GSH and blood pressure among women at risk for pre-eclampsia.

Topics: Adolescent; Adult; Biomarkers; Calcium Carbonate; Calcium, Dietary; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation Mediators; Insulin Resistance; Iran; Maternal Nutritional Physiological Phenomena; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Premature Birth; Prevalence; Risk; Young Adult

This study was designed to assess the beneficial effects of high-dose (cholecalciferol) vitamin D supplementation on metabolic profiles and pregnancy outcomes among pregnant women at risk for pre-eclampsia. This randomized double-blind placebo-controlled clinical trial was performed among 60 pregnant women at risk for pre-eclampsia according to abnormal uterine artery Doppler waveform. Subjects were randomly divided into 2 groups to receive 50 000 IU vitamin D supplements (n=30) or receive placebo (n=30) every 2 weeks from 20 to 32 weeks of gestation. Fasting blood samples were taken at baseline study and 12 weeks after the intervention to quantify relevant variables. Newborn's anthropometric measurements were determined. Pregnant women who received cholecalciferol supplements had significantly increased serum 25-hydroxyvitamin D concentrations (+17.92±2.28 vs. +0.27±3.19 ng/ml, p<0.001) compared with the placebo. The administration of cholecalciferol supplements, compared with the placebo, resulted in significant differences in serum insulin concentrations (+1.08±6.80 vs. +9.57±10.32 μIU/ml, p<0.001), homeostasis model of assessment-insulin resistance (HOMA-IR) (+0.19±1.47 vs. +2.10±2.67, p<0.001), homeostatic model assessment-beta cell function (HOMA-B) (+5.82±29.58 vs. +39.81±38.00, p<0.001) and quantitative insulin sensitivity check index (QUICKI) score (-0.009±0.03 vs. -0.04±0.03, p=0.004). Furthermore, cholecalciferol-supplemented pregnant women had increased HDL-cholesterol concentrations (+2.67 ± 8.83 vs. -3.23±7.76 mg/dl, p=0.008) compared with the placebo. Finally, cholecalciferol supplementation led to a significant rise in plasma total antioxidant capacity (TAC) concentrations (+79.00±136.69 vs. -66.91±176.02 mmol/l, p=0.001) compared with the placebo. Totally, the administration of cholecalciferol supplements among pregnant women at risk for pre-eclampsia for 12 weeks had favorable effects on insulin metabolism parameters, serum HDL-cholesterol, and plasma TAC concentrations.

Topics: Adult; Antioxidants; C-Reactive Protein; Cholecalciferol; Cholesterol, HDL; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Risk Factors

Increased metabolic profiles during pregnancy are associated with an increased risk of maternal and neonatal morbidity and remain a significant medical challenge. To our knowledge, no reports are available indicating the effects of calcium-vitamin D supplementation on metabolic profiles among pregnant women at risk for pre-eclampsia. This study was designed to determine the effects of consumption calcium-vitamin D supplements on metabolic profiles among Iranian pregnant women at risk for pre-eclampsia. This randomized single-blind controlled clinical trial was performed among 49 pregnant women at risk for pre-eclampsia, primigravida, aged 18-35 year old who were carrying singleton pregnancy at their third trimester. Subjects were randomly assigned to consume the placebo (n = 25) or calcium-vitamin D supplements (n = 24) for 9 weeks. Calcium-vitamin D supplements were containing 500 mg carbonate calcium plus 200 IU vitamin D3. Fasting blood samples were taken at baseline and after 9 week intervention to measures of Fasting Plasma Glucose (FPG) and serum lipid profiles. Consumption of calcium-vitamin D supplements resulted in decreased FPG and serum triglycerides levels as compared to the placebo (-9.1 vs. 0.5 mg dL(-1); p = 0.03, -11.7 vs. 49.9 mg dL(-1); p = 0.001, respectively). No significant differences were found comparing calcium-vitamin D supplements and the placebo in terms of their effect on serum total-, HDL-, LDL-cholesterol levels. Within-group differences in the placebo group revealed a significant increase in serum triglycerides levels (+49.9 mg dL(-1), p < 0.0001). In conclusion, consumption of calcium-vitamin D supplements for 9 weeks during pregnancy among pregnant women at risk for pre-eclampsia resulted in decreased FPG and serum triglycerides levels as compared to the placebo group, but could not affect serum total-, HDL-, LDL-cholesterol levels.

Topics: Adolescent; Adult; Biomarkers; Blood Glucose; Calcium Carbonate; Cholecalciferol; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dietary Supplements; Drug Combinations; Female; Humans; Iran; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Risk Factors; Single-Blind Method; Time Factors; Treatment Outcome; Triglycerides; Young Adult

Using an angiotensin sensitivity test we carried out a prospective study in an attempt to predict the possible onset of preeclampsia and to prevent it by calcium supplementation (elemental calcium 156 or 312 mg/day per os) and treatment with vitamin D3 (0.5 micrograms/3 day per os).. We used a study design in which 666 singleton pregnant women were managed with conventional antenatal care and 210 singleton pregnant women were managed with a protocol, together with conventional antenatal care.. Of the 666 women managed conventionally, 113 (16.9%) developed preeclampsia. However, the incidence of preeclampsia in the 210 women managed on the protocol was lower, at 10.9%.. Our findings indicate that this protocol for the prediction and prevention of preeclampsia is useful for pregnant women at high risk of developing preeclampsia.

Topics: Adult; Angiotensin II; Blood Pressure; Calcium; Causality; Cholecalciferol; Clinical Protocols; Female; Humans; Incidence; Parity; Pre-Eclampsia; Pregnancy; Pregnancy, High-Risk; Prospective Studies

Preeclampsia is one of the main contributers to maternal and fetal morbidity and mortality during pregnancy. A history of preeclampsia puts mother and offspring at an increased cardiovascular risk in later life. We hypothesized that at the time of birth functional impairments of fetal endothelial cells can be detected in pregnancies complicated by preeclampsia and that a therapeutic intervention using 1,25 (OH)2 vitamin D3 can reverse the adverse effects of preeclampsia on cell function.. Human umbilical vein endothelial cells (HUVEC) were isolated from umbilical cords obtained from preeclamptic (N = 12) and uncomplicated pregnancies (N = 13, control). Placental villous tissue fragments from uncomplicated term pregnancies were incubated in explant culture for 48 h at 2% (hypoxia), 8% or 21% O2. Explant conditioned media (CM) was collected and pooled according to oxygen level. We compared the ability of preeclampsia vs. control HUVEC to migrate, proliferate, and form tubule-like networks in a Matrigel assay, in the presence/absence of CM and 1,25(OH)2 vitamin D3.. HUVEC from preeclamptic pregnancies showed reduced migration (P = 0.04) and tubule formation (P = 0.04), but no change in proliferation (P = 0.16) compared to healthy pregnancies. Placental villous explant CM derived from 2% O2 incubations significantly reduced HUVEC migration, when compared to non-CM (P = 0.04). Vitamin D3 improved HUVEC function in neither of the groups. There was no significant difference in VEGF gene expression between healthy and preeclamptic pregnancies and no effect of Vitamin D3 on VEGF expression.. Reduced functional abilities of fetal endothelial cells from preeclamptic pregnancies suggests that disease pathways, possibly originating from the dysfunctional placenta, negatively impact fetal endothelium. The neutral effect of 1,25(OH)2 vitamin D3 contrasts with previous findings that vitamin D rescues the poor migration, proliferation and tubule formation exhibited by cord blood fetal endothelial progenitor cells from preeclamptic pregnancies. Further investigations to distinguish pathways by which offspring exposed to preeclampsia are at risk for cardiovascular disease are needed.

Topics: Adult; Cell Movement; Cell Proliferation; Cells, Cultured; Cholecalciferol; Culture Media, Conditioned; Female; Fetal Blood; Gene Expression Regulation, Developmental; Human Umbilical Vein Endothelial Cells; Humans; Hypoxia; Male; Neovascularization, Physiologic; Polymerase Chain Reaction; Pre-Eclampsia; Pregnancy; Tissue Culture Techniques; Vascular Endothelial Growth Factor A

Obesity is a worldwide individual and public health issue, and contributes to the development of numerous chronic diseases. In particular, maternal obesity has harmful effects on both the mother and child during and after pregnancy. The digestion and metabolism of food are controlled by endocrine factors, including insulin, glucagon and estrogen. These hormonal factors are differentially regulated during pregnancy due to the specialized hormonal environment during this period. In the present study, we examined the effects of 1,25-dihydroxyvitamin D3 (VD3), an active hormonal form of nutritional vitamin D3, on lipid metabolism in pregnant rats. The body weight of rats treated with VD3 was significantly reduced compared to that of the rats in the control group. In addition, histological analysis demonstrated that the amount of fat stored in adipocytes was reduced by treatment with VD3. To determine the role of VD3 in lipid metabolism, the expression levels of lipid metabolism‑associated genes were measured in the rat adipose tissue and liver. VD3 negatively regulated the expression of various lipogenic genes, including fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD1) and acetyl-CoA carboxylase 1 (ACC1), in both the adipose tissue and liver. However, the regulators of lipogenic enzymes such as, sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-γ (PPAR-γ) and insulin-induced gene 2 (INSIG2) were differentially regulated by VD3 in a tissue‑specific manner. On the whole, these findings suggest that VD3 regulates lipid metabolism and deposition in the liver and adipose tissue, and thereby reduces fat in pregnant animals, as well as body weight. Our results suggest that the alteration of lipogenesis through the administration of VD3 may help to reduce excessive weight gain during pregnancy and prevent obesity‑related pregnancy complications such as pre-eclampsia, gestational diabetes, hypertension and issues with labor.

Topics: Adipose Tissue; Animals; Cholecalciferol; Female; Gene Expression Regulation; Lipogenesis; Liver; Obesity; Pre-Eclampsia; Pregnancy; Rats; Rats, Sprague-Dawley

The main pathogenic feature of preeclampsia is maternal endothelial dysfunction that results from impaired angiogenesis and reduced endothelial repair capacity. In addition, preeclampsia risk is associated with vitamin D deficiency. We hypothesized that vitamin D(3) stimulates proangiogenic properties of endothelial colony-forming cells (ECFCs). ECFCs were obtained and cultured from cord blood and characterized by immunocytochemistry and flow cytometry. Proliferation, total length of tubule formation on Matrigel, expression of VEGF mRNA, and pro-matrix metalloproteinases (MMP)-2 activity were assessed after treatment of ECFCs with vitamin D(3). Specificity of the observed effects was tested by blocking the vitamin D receptor (VDR) or the VEGF signaling pathway. ECFCs treated with 10 nM vitamin D(3) showed a 1.27 times higher tubule formation compared with vehicle-treated controls (1.27 ± 0.19) as well as a 1.36 times higher proliferation rate (1.36 ± 0.06). Vitamin D(3) induced pro-MMP-2 activity (1.29 ± 0.17) and VEGF mRNA levels (1.74 ± 0.73) in ECFCs. VDR blocking by pyridoxal-5-phosphate (0.73 ± 0.19) or small interfering RNA (0.75 ± 0.17) and VEGF inhibition by Su5416 (0.56 ± 0.16) or soluble fms-like tyrosine kinase-1 (0.7 ± 0.14) reduced tubule formation and pro-MMP-2 activity (pyridoxal-5-phosphate: 0.84 ± 0.09; Su5416: 0.79 ± 0.11; or sFlt: 0.88 ± 0.13). This effect was neutralized by vitamin D(3). Consequently, vitamin D(3) significantly promoted angiogenesis in ECFCs in vitro possibly due to an increase in VEGF expression and pro-MMP-2 activity. Since angiogenesis is a crucial feature in the pathophysiology of preeclampsia these findings could explain the positive influence of vitamin D(3) in reducing preeclampsia risk.

Topics: Angiogenesis Inhibitors; Cell Proliferation; Cells, Cultured; Cholecalciferol; Endothelial Cells; Female; Fetal Blood; Flow Cytometry; Humans; Immunohistochemistry; Indoles; Matrix Metalloproteinase 2; Neovascularization, Physiologic; Pre-Eclampsia; Pregnancy; Pyridoxal Phosphate; Pyrroles; Receptors, Calcitriol; Risk; Signal Transduction; Stem Cells; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1

The aim of this study was to analyze the hormonal basis for low 1,25(OH)2D3 circulating levels in patients with preeclampsia and/or preterm deliveries. The activity and expression of the 1 alphaOHase, 25-OHase, 24-OHase and VDR in the placental tissue of normal pregnancies, preeclampsia-complicated pregnancies and premature births were investigated. The mRNA of the enzymes was detected in the placental tissue from preeclamptic pregnancies and compared to those of normal placental tissue. Real time PCR analysis showed a significant increased 1 alpha-OHase gene expression in preeclamptic patients, and the gene expression of 24-OHase was significantly decreased. With regard to the 25-OHase the median value of the normal placental tissue was significantly higher than in the placental tissue of preeclamptic patients. The real time analysis of all target genes also showed significant differences in normal placental tissue compared to placental tissue from premature births (VDR: p = 0.041; 1 alpha-OHase: p = 0.013; 24-OHase: p = 0.007; 25-OHase p = 0.027). Our observation of reduced VDR expression on mRNA level in placental tissue indicates a possible dependence of the modulation of VDR expression from proliferation and differentiation processes. It can be speculated whether the down-regulation of VDR in the examined placenta cells was the result of an altered production of calcitriol by these cells. We found a significantly higher 1 alpha-OHase-expression in the placental tissue of pregnant women with preeclampsia or preterm birth compared to healthy pregnant women, whereas the expression of 25-OHase was significantly reduced. These results correlate with other studies and support the significance of the placenta regarding metabolism malfunctions as they were observed in the calcium metabolism for preeclampsia. That a placenta with preeclampsia expresses less 1 alpha-OHase-mRNA and shows less 1 alpha-OHase-activity than in placental samples of inconspicuous placentae, can be granted as a specific alteration in the placental ability to synthesize adequate amounts of 1,25(OH)2D3.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Calcium; Case-Control Studies; Cholecalciferol; Female; Gene Expression; Humans; Placenta; Pre-Eclampsia; Pregnancy; Premature Birth; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger