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Low maternal vitamin D levels during pregnancy have been linked to various health outcomes in the offspring, ranging from periconceptional effects to diseases of adult onset. Maternal and infant cord 25(OH)D levels are highly correlated. Here, we review the available evidence for these adverse health effects. Most of the evidence has arisen from observational epidemiological studies, but randomized controlled trials are now underway. The evidence to date supports that women should be monitored and treated for vitamin D deficiency during pregnancy but optimal and upper limit serum 25(OH)D levels during pregnancy are not known.
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... Despite numerous studies linking vitamin D deficiency to long-term health issues in offspring [1][2][3][4] and an increased risk of pregnancy complications like preeclampsia (PE), fetal growth retardation (FGR), and preterm birth [5][6][7][8][9][10][11][12][13][14], vitamin D deficiency remains common among pregnant women in both high-and low-income countries [15]. Placental development and function are essential for pregnancy outcome and closely related to conditions such as PE and FGR [16,17]. ...
... Vitamin D deficiency in uncomplicated pregnancies is associated with long-term health difficulties, including asthma, type 1 diabetes, multiple sclerosis, and respiratory infections in the affected children [2,4,56,57], which are all conditions related to the immune function of the offspring. Whether these effects are more likely to be caused by placental changes or occur as a consequence of an insufficient vitamin D supply to the fetus remains to be clarified. ...
... Neurodevelopmental disorders like autism spectrum disorders, attention deficit hyperactivity disorder, and schizophrenia have previously been associated with intrauterine vitamin D deficiency [2,3]. Supporting these findings, our gene set enrichment analysis further identified six genes involved in pathways linked to autism spectrum disorders and schizophrenia. ...
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Vitamin D deficiency is a highly prevalent obstetrical concern associated with an increased risk of complications like pre-eclampsia, gestational diabetes, and growth retardation. Vitamin D status in pregnancy is also linked to long-term offspring health, e.g., the risk of obesity, metabolic disease, and neurodevelopmental problems. Despite the suspected role of vitamin D in placental diseases and fetal development, there is limited knowledge on the effect of vitamin D on placental function. Thus, we performed next-generation RNA sequencing, comparing the placental transcriptome from uncomplicated term pregnancies receiving the often-recommended dose of 10 µg vitamin D/day (n = 36) with pregnancies receiving 90 µg/day (n = 34) from late first trimester to delivery. Maternal vitamin D status in the first trimester was also considered. We found that signaling pathways related to cell adhesion, immune function, and neurodevelopment were affected, supporting that increased vitamin D supplementation benefits placental function in established pregnancies without severe vitamin D deficiency, also underlining the importance of vitamin D in brain development. Specific effects of the first trimester vitamin D status and offspring sex were also identified. Further studies are warranted, addressing the optimal vitamin status during pregnancy with a focus on organ-specific vitamin D needs in individual pregnancies.
... Vitamin D deficiency is quite common in the general population, and its prevalence in the pregnant population has been known for a long time. [27] Vitamin D has been associated with many negative health outcomes, starting from the preconception period, pregnancy, perinatal period, childhood and adulthood. [27,28] There is also increasing evidence regarding the role of adequate vitamin D levels in maintaining normal glucose homeostasis. ...
... [27] Vitamin D has been associated with many negative health outcomes, starting from the preconception period, pregnancy, perinatal period, childhood and adulthood. [27,28] There is also increasing evidence regarding the role of adequate vitamin D levels in maintaining normal glucose homeostasis. It has been observed in the literature that studies evaluating the effect of vitamin D deficiency in patients with gestational diabetes have contradictory results. ...
Article
Aim: According to few studies which tried to evaluate mean platelet volume (MPV) and 25 hydroxy vitamin D, have shown conflicting results in gestational diabetic patients. In this study we aimed to compare main platelet volume and 25 hydroxy vitamin D values between gestational diabetic patients and healty individual pregnant womens. Material and method: The patients were selected from 24-28 weeks pregnant people who made gestational diabetes screening and oral glucose tolerance test from obstetric-gynecology, diabetes and endocrinology polyclinics of Okmeydanı Training and Research Hospital. After the searching 52 gestational diabetic patients and 52 healty pregnant women included to the study. We estimated MPV and vitamin D level. In addition, demographic and clinical data of subjects were recorded. Results: Mean platelet volume (MPV) value was found 8,5 ± 1,0 fl and 8,3 ± 1,1 fl. in gestational diabetic and control group respectively. There was no statistically significant differences in MPV value between case and the control group (p>0.05). Mean 25 hydroxy vitamin D value was found 20.5 ± 11.0 ng/ml and 21,1 ± 9,3 ng/ml. gestational diabetic and control group respectively. There was no statistically significant differences in 25 hydroxy (OH) vitamin D value between case and control group. Conclusion: In our study we found no statistically significant differences in MPV and 25-OH vitamin D values between gastational diabetic pregnant group and healty pregnant group.
... Over the years, observational studies have repeatedly linked maternal vitD deficiency to various adverse pregnancy outcomes like gestational diabetes, pre-eclampsia and fetal growth restriction [1][2][3][4][5]. In offspring, an insufficient vitD level in pregnancy is not only related to negative effects on bone development; numerous studies have also shown an increased risk of long-term health problems, such as diabetes, asthma, overweight and neurodevelopmental disorders [6][7][8][9]. ...
... From a health perspective, our findings are of high clinical relevance as a sufficient fetal and neonatal vitD status is important for bone health [44,45]. Furthermore, intrauterine vitD exposure may potentially reduce later-life disease risk by strengthening the immune system [46], thereby potentially reducing the risk of immune-system-related conditions like type 1 diabetes, asthma and allergy [6,9,47]. VitD insufficiency during pregnancy and the first vulnerable years of life also markedly increases the risk of common and potentially fatal infections such as respiratory syncytial virus (RSV) [48]. ...
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Vitamin D (vitD) deficiency (25-hydroxy-vitamin D < 50 nmol/L) is common in pregnancy and associated with an increased risk of adverse pregnancy outcomes. High-dose vitD supplementation is suggested to improve pregnancy health, but there is limited knowledge about the effects on placental vitD transport and metabolism and the vitD status of newborns. Comparing the current standard maternal supplementation, 10 µg/day to a 90 µg vitD supplement, we investigated placental gene expression, maternal vitD transport and neonatal vitD status. Biological material was obtained from pregnant women randomized to 10 µg or 90 µg vitD supplements from week 11–16 onwards. Possible associations between maternal exposure, neonatal vitD status and placental expression of the vitD receptor (VDR), the transporters (Cubilin, CUBN and Megalin, LRP2) and the vitD-activating and -degrading enzymes (CYP24A1, CYP27B1) were investigated. Maternal vitD-binding protein (VDBP) was determined before and after supplementation. Overall, 51% of neonates in the 10 µg vitD group were vitD-deficient in contrast to 11% in the 90 µg group. High-dose vitD supplementation did not significantly affect VDBP or placental gene expression. However, the descriptive analyses indicate that maternal obesity may lead to the differential expression of CUBN, CYP24A1 and CYP27B1 and a changed VDBP response. High-dose vitD improves neonatal vitD status without affecting placental vitD regulation.
... Vitamin D is a steroid hormone and 25-hydroxyvitamin D [25(OH)D] is the main circulating form of vitamin D [7], and recent revised guidelines of the North American Society of Endocrinology define vitamin D deficiency as blood levels of less than 20 ng/ml and vitamin D insufficiency as having a 25(OH)D level of 20-30 ng/ml [8]. Vitamin D is mainly known for its regulation of calcium and phosphate absorption from the gastrointestinal tract and mineralization in the skeletal system [9]. In addition to this, vitamin D is an overall regulator of immune, reproductive and other systems, including the regulation of maternal-fetal immune imbalance disease leading to RSA [10,11]. ...
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Background To investigate the mechanism of vitamin D level on the regulation of peripheral blood lymphocyte subsets and serum Th1/Th2 cytokines in patients with unexplained recurrent spontaneous abortion (URSA). Methods Eighty female patients with URSA attending Sichuan Jinxin Xinan Women's and Children's Hospital from January 2020 to May 2021 were selected as the study group, and 30 age-matched women with a history of healthy deliveries were chosen as the control group, and peripheral blood lymphocyte subpopulations and serum Th1/Th2 cytokines of people with different levels of vitamin D were detected in the study group by flow cytometry, respectively. The results of immune factors before and after supplementation were analyzed in 40 of these patients with low vitamin D levels. The results of lymphoid subpopulations and Th1/Th2 cytokines in 19 patients with normal pregnancy before and after vitamin D supplementation and after normal pregnancy were also analyzed comparatively. Results (1) Serum 25(OH)D in the study group was lower than in the control group; peripheral blood Th cells, B cells and NK cells in the study group were higher than in the control group; IL-2, TNF-α, IFN-γ and IL-6 in the study group were higher than in the control group, while IL-4 and IL-10 in the study group were lower than in the control group (P < 0.05). (2) Th cells, B cells and NK cells of URSA patients in the vitamin D low level group were higher than those in the vitamin D normal group; serum cytokines IL-2, TNF-α and IFN-γ of patients in the vitamin D low level group were higher than those in the vitamin D normal group (P < 0.05); (3) Th cells, B cells and NK cells in URSA patients after vitamin D supplementation were lower than before vitamin D supplementation; serum cytokines IL-2, TNF-α and IFN-γ after vitamin D supplementation were lower than before vitamin D supplementation, IL-4 and IL-10 after vitamin D supplementation were higher than before vitamin D supplementation (P < 0.05), and there was no significant difference in IL-6 before and after vitamin D supplementation. (4) Th cells, B cells and NK cells in patients with normal pregnancy after vitamin D supplementation and after pregnancy were lower than those before vitamin D supplementation; serum cytokines IL-2, TNF-α and IFN-γ after vitamin D supplementation and after pregnancy were lower than those before vitamin D supplementation, and serum cytokines IL-4 and IL-10 after vitamin D supplementation and after pregnancy were higher than those before vitamin D supplementation, TNF -α, IFN-γ after pregnancy were lower than after vitamin D supplementation (P < 0.05), IL-6 was not significantly different before and after vitamin D supplementation and after pregnancy. Conclusion Vitamin D deficiency rate was high in URSA patients. Th、B、NK cells and IL-2, TNF-α, IFN-γ, IL-6 cytokines were high, while IL-6 and IL-10 were low in URSA patients. IL-2, TNF-α, IFN-γ cytokines and Th, B, NK cells were increased in vitamin D deficient URSA patients, and Vitamin D deficiency may be an important cause or aggravating factor of immune dysfunction in URSA patients. Vitamin D has an immunomodulatory effect on URSA patients, promoting successful pregnancy by down-regulating peripheral blood Th, B, and NK cells and IL-2, TNF-α, and IFN-γ cytokines, while up-regulating IL-4 and IL-10.
... Vitamin D supplementation during pregnancy has shown mixed and controversial results in improving these outcomes [13,14]. Some studies suggest that supplementation may improve birth length, operative delivery and preeclampsia [11,12] and monitoring and treatment have been recommended during pregnancy [15]. While others have not found significant associations with these outcomes or have mentioned limited evidence on the effects of vitamin D supplementation [11,12,16,17]. ...
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Background Maternal vitamin D deficiency during pregnancy has been associated with various maternal adverse events (MAE). However, the evidence regarding the effect of vitamin D supplementation on these outcomes is still inconclusive. Methods This secondary analysis utilized a case–control design. 403 samples with MAE and 403 samples without any outcomes were selected from the Khuzestan Vitamin D Deficiency Screening Program in Pregnancy study. Random forest (RF) analysis was used to evaluate the effect of maternal vitamin D changes during pregnancy on MAE. Results The results showed that women who remained deficient (35.2%) or who worsened from sufficient to deficient (30.0%) had more MAE than women who improved (16.4%) or stayed sufficient (11.8%). The RF model had an AUC of 0.74, sensitivity of 72.6%, and specificity of 69%, which indicate a moderate to high performance for predicting MAE. The ranked variables revealed that systolic blood pressure is the most important variable for MAE, followed by diastolic blood pressure and vitamin D changes during pregnancy. Conclusion This study provides evidence that maternal vitamin D changes during pregnancy have a significant impact on MAE. Our findings suggest that monitoring and treatment of vitamin D deficiency during pregnancy may be a potential preventive strategy for reducing the risk of MAE. The presented RF model had a moderate to high performance for predicting MAE.
... Although VD belongs among these nutrients, the exact mechanisms that mediate VD insufficiency and the development of adverse maternal and offspring effects have not to date been clarified [25]. Insufficient prenatal and neonatal 25(OH)D concentrations can increase the risk of schizophrenia, type 1 diabetes, multiple sclerosis, cancer, asthma, and skeletal development in later life [26]. Due to the latter, there is global concern about the impact of inadequate VD concentrations on pregnancy outcomes, fetal development, and health status in childhood and adult life. ...
Article
Vitamin D (VD) plays a crucial role in regulating calcium homeostasis, while the wealth of its pleiotropic actions is gaining increasing research interest. Sufficient VD concentrations are of clinical relevance, particularly in the context of physiological alterations, such as those occurring during pregnancy when maternal VD is the sole source for the developing fetus. As a result, inadequate VD concentrations in pregnancy have been associated with perinatal complications and adverse neona-tal outcomes, including preeclampsia, gestational diabetes mellitus, increased rates of cesarean section, low birth weight, small-for-gestational-age infants, poor immune and skeletal growth, allergies, and respiratory infections. Over the past few decades, several observational studies have underlined the important role of maternal VD in the neural, musculoskeletal, and psychomotor growth and bone health of the offspring. However, the complexity of the factors involved in regulating and assessing VD homeostasis, including race, sun exposure, dietary habits, and laboratory measurement techniques, makes the interpretation of relevant research findings challenging. The aim of this narrative review is to summarize the evidence on the importance of VD in maintaining optimal health during pregnancy, infancy, childhood, and adolescence.
... It is accepted that determining serum level 25-hydroxyvitamin [25(OH)D] serves as the best method for evaluating vitamin D status [5,6]. To date, there is no global consensus on reference values for 25(OH)D levels used to identify a vitamin D deficiency and insufficiency in pregnancy [7,8]. Sufficiency is defined by different serum levels of 25(OH)D: 20-50 ng/mL by I U.S. Institute of Medicine (IOM) [9], and 30 ng/mL by the U.S. Endocrine Society [10], whereas other studies proposed threshold reference values of 40 ng/mL [11,12] or 50 ng/mL to provide a broader spectrum of benefits, especially for the immune system [13,14]. ...
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Maternal vitamin D deficiency, which is highly prevalent in pregnant women in Europe, is linked to adverse health effects for both the mother and child. The objective was to assess vitamin D status in pregnant women by evaluating their dietary and supplemental vitamin D intake, serum vitamin D levels, parathyroid hormone levels, and lifestyle factors. This cross-sectional study, with a total of 735 participants (145 pregnant and 590 up to the seventh day postpartum), took place in Latvia. Blood samples, a food frequency questionnaire, and medical documentation were used for data collection. The median serum vitamin D concentration was 34.0 ng/mL, with pregnant women having higher levels (42.9 ng/mL) than postpartum women (31.8 ng/mL). There was no association between vitamin D serum concentration and dietary intake of vitamin D (p > 0.05), whereas there was a significant correlation with use of vitamin D supplements (r = 0.41; p < 0.001 in pregnant women and r = 0.35; p < 0.001 in postpartum women). This study demonstrated that a minority of pregnant women (21.9%) had optimal serum vitamin D concentration (>45 ng/mL), and diet had no significant impact on vitamin D levels. Thus, our proposed recommendation for vitamin D intake during pregnancy was 63 mcg (2500 IU) year-round for optimal levels in pregnant women in Northeastern Europe.
Article
Pandemic D-avitaminosis swept the planet. Among the inhabitants of the northern hemisphere, about 45 % are deficient, and 32 % have insufficient vitamin D serum levels. In Russia, the situation is even more tense: the level of deficiency was registered in 56.4 % of the population, and insufficiency in 27.87 % of our fellow citizens. Maintaining an optimal concentration of vitamin D in the blood serum reduces the risk and severity of autoimmune, cardiovascular diseases, many types of cancer, dementia, type 1 and 2 diabetes, respiratory tract infections, improves dental and oral health, and increases physical performance. The problem of the increased prevalence of vitamin D deficiency during pregnancy, which has serious consequences not only for the mother, but also for the child throughout later life, requires special attention. A review of the documents regulating the intake of vitamin D supplements suggests that there is some uncertainty in the instructions, which leads to a wide variability in medical recommendations to patients on the choice of the type of drug, its dosage and the duration of vitamin D intake. Recommendations on the required duration of vitamin D supplementation, in our opinion, look the most vulnerable and insufficiently substantiated, therefore, in this work, on the basis of international clinical practice, studies of the dynamics of the increment in the level of vitamin D were carried out and a method was developed for calculating the required duration of taking the most common vitamin D3 preparations at present. The analysis of domestic and foreign practice of increasing the level of vitamin D in the blood serum, as well as the conducted statistical studies, allow, with some caution, to draw the following conclusions. When taking vitamin D3 preparations, the increase in the level of 25(OH)D over time is quite correctly described by an exponential equation. As the duration of taking vitamin D3 preparations increases, the rate of increase in the level of 25(OH)D in the blood serum decreases. The current calcifediol level when taking in vitamin D3 preparations in asymptotical persons, is associated with a power-law dependence on the daily drug dose and increases as it increases. As shown by numerous results of clinical trials, the main increase in the level of 25(OH)D occurs within 30–90 days under different conditions. The multiple regression equation we obtained indicates that the time of blood serum saturation with vitamin D3 is inversely related to the daily dose of the drug, the patient’s age, and the initial level of 25(OH)D in the blood serum. The method developed by the authors makes it possible to estimate the dynamics of the increase in the level of 25(OH)D in the patient’s blood serum as vitamin D3 preparations are taken and to determine the required duration of the drug intake.
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Background: Vitamin D deficiency is prevalent in India, a finding that is unexpected in a tropical country with abundant sunshine. Vitamin D deficiency during pregnancy has important implications for the newborn and infant. There are few data from India about the prevalence of hypovitaminosis D in pregnancy and in the newborn. Objective: Our aim was to determine the prevalence of osteomalacia and hypovitaminosis D in pregnancy and in cord blood and to correlate maternal 25-hydroxyvitamin D [25(OH)D] status with sun exposure, daily calcium intake (dietary plus supplemental), and intact parathyroid hormone (PTH) concentrations. Design: Serum calcium, inorganic phosphorus, 25(OH)D, heat-labile alkaline phosphatase, and PTH were studied in 207 urban and rural pregnant subjects at term. Alkaline phosphatase and 25(OH)D were measured in the cord blood of 117 newborns. Results: Mean maternal serum 25(OH)D was 14 ± 9.3 ng/mL, and cord blood 25(OH)D was 8.4 ± 5.7 ng/mL. PTH rose above the normal range when 25(OH)D was <22.5 ng/mL. Eighty-four percent of women (84.3% of urban and 83.6% of rural women) had 25(OH)D values below that cutoff. Fourteen percent of the subjects had elevated alkaline phosphatase (17% of urban and 7% of rural subjects). Calcium intake was uniformly low, although higher in urban (842 ± 459 mg/d) than in rural (549 ± 404 mg/d) subjects (P < 0.001). Maternal serum 25(OH)D correlated positively with cord blood 25(OH)D (r = 0.79, P < 0.001) and negatively with PTH (r = −0.35, P < 0.001). Conclusion: We observed a high prevalence of physiologically significant hypovitaminosis D among pregnant women and their newborns, the magnitude of which warrants public health intervention.
Article
In utero or early-life vitamin D deficiency is associated with skeletal problems, type I diabetes, and schizophrenia, but the prevalence of vitamin D deficiency in U.S. pregnant women is unexplored. We sought to assess vitamin D status of pregnant women and their neonates residing in Pittsburgh by race and season. Serum 25-hydroxyvitamin D 125(OH)D) was measured at 4-21 wk gestation and predelivery in 200 white and 200 black pregnant women and in cord blood of their neonates. Over 90% of women used prenatal vitamins. Women and neonates were classified as vitamin D deficient [25(OH) < 37.5 nmol/L], insufficient [25(OH)D 37.5-80 nmol/L], or sufficient [25(OH)D > 80 nmol/L]. At delivery, vitamin D deficiency and insufficiency occurred in 29.2% and 54.1% of black women and 45.6% and 46.8% black neonates, respectively. Five percent and 42.1% of white women and 9.7% and 56.4% of white neonates were vitamin D deficient and insufficient, respectively. Results were similar at < 22 wk gestation. After adjustment for prepregnancy BMI and periconceptional multivitamin use, black women had a smaller mean increase in maternal 25(OH)D compared with white women from winter to summer (16.0 +/- 3.3 nmol/L vs. 23.2 +/- 3.7 nmol/L) and from spring to summer (13.2 +/- 3.0 nmol/L vs. 27.6 +/- 4.7 nmol/L) (P < 0.01). These results suggest that black and white pregnant women and neonates residing in the northern US are at high risk of vitamin D insufficiency, even when mothers are compliant with prenatal vitamins. Higher-dose supplementation is needed to improve maternal and neonatal vitamin D nutnture.
Article
Background: Although Vitamin D is best known as a calcium homeostasis modulator, it also has immune modulating potential, as shown by its protective effect against MS development, supported by reduced disease risk associated with sun exposure and Vitamin D supplement use. Elevated Vitamin D blood levels have also been associated with lower risk of MS. Objective: To study the immunomodulatory effects of Vitamin D in MS. Methods: Serum 25(OH)D3 and 1,25(OH)2D3 levels were measured using ELISA in 58 relapsing remitting MS (RRMS) patients during remission, 34 RRMS patients during relapses, 40 primary progressive MS (PPMS) subjects and 60 healthy controls. Cell proliferation was measured using [3H]-thymidine incorporation assays. Vitamin D receptor (VDR), α1-hydroxylase, and indoleamine 2,3-dioxygenase (IDO) expression was measured by RT-PCR, while cytokine production was evaluated using ELISPOT. CD4+CD25+ regulatory T cells were studied using flow cytometry. Results: 25(OH)D3 and 1,25(OH) 2D3 levels were significantly lower in RRMS patients than in controls, more during relapses than remissions. By contrast, PPMS patients showed similar levels to controls. Proliferation of both freshly isolated CD4+ T cells and MBP-specific T cells was inhibited by 1,25(OH)2D 3. Activated Vitamin D also enhanced IL-10 producing cell development, and reduced IL-6, and IL-17 secreting cell numbers. 1,25(OH) 2D3 induced VDR expression in both activated and resting cells. Interestingly, T cells metabolized 25(OH)D3 into biologically active 1,25(OH)2D3, since they constitutively express α1-hydroxylase. Finally, 1,25(OH)2D3 also increased expression and biological activity of IDO, triggering significant increase in the number of CD4+CD25+ regulatory T cells. Conclusions: 1,25(OH) 2D3 plays an important role in T cell homeostasis during RRMS. Correction of its deficiency may prove useful in the treatment of the disease.
Article
Mouse myeloid leukemia cells can be induced to differentiate into macrophages in vitro by 1 alpha,25-dihydroxyvitamin D3, the active form of vitamin D3. The minimal concentration of 1 alpha,25-dihydroxyvitamin D3 to induce the cell differentiation was 0.12 nM. The degree of cell differentiation in various markers induced by 12 nM 1 alpha,25-dihydroxyvitamin D3 was nearly equivalent to that induced by 1 microM dexamethasone, the most potent known stimulator. Among several markers of the differentiation by 1 alpha,25-dihydroxyvitamin D3, phagocytic activity was induced within 24 hr, and this was followed by induction of lysozyme and locomotive activities. Similar changes were also induced by 0.01-1 microM 1 alpha-hydroxyvitamin D3. 25-Hydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3 showed only weak inducing activity. These results suggest the possibility that, in addition to its wellknown biological activities in enhancing intestinal calcium transport and bone mineral mobilization, 1 alpha, 25-dihydroxyvitamin D3 is involved in the differentiation of bone marrow cells.