Vitamin D deficiency may be a risk factor for recurrent pregnancy losses by increasing cellular immunity and autoimmunity

Ota, Kuniaki; Dambaeva, Svetlana; Han, Ae Ra; Beaman, Kenneth D.; Gilman‐Sachs, Alice; Kwak‐Kim, Joanne

doi:10.1093/humrep/det424

Cited by 170 publications

(205 citation statements)

References 71 publications

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“…In a retrospective cross sectional study of 133 women diagnosed with recurrent pregnancy loss, Ota et al [21] reported that 63 out of 133 women (47.4 %) had hypovitaminosis D (less than 30 ng/ml) and that NK cell levels and NK cytotoxicity at effector to target cell (E:T) ratio of 25:1 were significantly higher in the low vitamin D group when compared with subjects with normal vitamin D levels. In addition, in vitro NK cytotoxicity assays demonstrated significant suppression at an E:T ratio of 50:1 when treated with Vitamin D compared to the control group, demonstrating evidence that low Vitamin D may be associated with increased NK cell activity in women with recurrent pregnancy loss.…”

Section: Pregnancy Lossmentioning

confidence: 99%

Vitamin D and assisted reproduction: should vitamin D be routinely screened and repleted prior to ART? A systematic review

Pacis

Fortin

Zarek

et al. 2014

J Assist Reprod Genet

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Purpose To review the current literature regarding the role of vitamin D status in pregnancy outcomes in women undergoing assisted reproductive technology (ART) and to assess cost-effectiveness of routine vitamin D deficiency screening and repletion prior to initiation of ART.Methods A systematic literature review was conducted using PubMed. Relevant study outcomes were compared among the selected studies. A cost-benefit analysis was performed using a decision tree mathematical model with sensitivity analyses from the perspective of direct societal cost. Published data were used to estimate probabilities and costs in 2014 US dollars. Results Thirty-four articles were retrieved, of which eight met inclusion criteria. One study demonstrated a negative relationship between vitamin D status and ART outcomes, while two studies showed no association. The remaining five studies concluded that ART outcomes improved after vitamin D repletion. Conclusion The majority of reviewed studies reported a decrement in ART outcomes in patients with vitamin D deficiency. Cost-benefit analyses suggested that screening and supplementing vitamin D prior to ART might be cost effective, but further evidence is needed. Given the absence of Level I evidence regarding vitamin D status and ART outcomes, full endorsement of routine vitamin D screening and supplementation prior to ART is premature.

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Section: Pregnancy Lossmentioning

confidence: 99%

Vitamin D and assisted reproduction: should vitamin D be routinely screened and repleted prior to ART? A systematic review

Pacis

Fortin

Zarek

et al. 2014

J Assist Reprod Genet

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“…In women with RPL, decreased vitamin D level was associated with the increased prevalence of antiphospholipid antibody, antinuclear antigen antibody, anti-ssDNA, and anti-thyroperoxidase antibody. In addition, peripheral blood CD19 + B and CD56 + NK-cell levels and NK cytotoxicity were significantly higher in women with low vitamin D level when compared with those of normal vitamin D level [6]. Normal pregnancy is associated with Th2 shift in T-cell immunity [7].…”

mentioning

confidence: 95%

“…In addition, vitamin D deficiency is a predisposing factor for various female diseases such as osteoporosis, uterine fibroids, endometriosis, and breast cancer and a risk factor for obstetrical complications such as gestational diabetes and preeclampsia [4,5]. Recently, we have reported that 47.4% of women with recurrent pregnancy losses (RPL) have vitamin D deficiency [6]. In women with RPL, decreased vitamin D level was associated with the increased prevalence of antiphospholipid antibody, antinuclear antigen antibody, anti-ssDNA, and anti-thyroperoxidase antibody.…”

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confidence: 99%

1,25‐Dihydroxy‐vitamin D3 regulates NK‐cell cytotoxicity, cytokine secretion, and degranulation in women with recurrent pregnancy losses

et al. 2015

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Vitamin D has a pivotal role in regulating immune responses by promoting Th2 immune responses and suppressing Th1 responses. Propensities to a Th1 immune response and increased NK-cell levels and cytotoxicity have been reported in women with recurrent pregnancy losses (RPL). In women with RPL, vitamin D deficiency is prevalent IntroductionVitamin D is a group of secosteroids and has a major role in maintaining skeletal health. Various effects of vitamin D on extra skeletal tissues have been reported as well, during the past decade [1]. Vitamin D deficiency is endemic for both men and women and across different age groups in the US population [2]. Low C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2015. 45: 3188-3199 Clinical immunology 3189vitamin D level has been linked to major common health problems in populations, particularly inflammatory conditions such as cardiovascular disease, cancers, diabetes, autoimmune diseases including multiple sclerosis, rheumatoid arthritis, and others [3]. In addition, vitamin D deficiency is a predisposing factor for various female diseases such as osteoporosis, uterine fibroids, endometriosis, and breast cancer and a risk factor for obstetrical complications such as gestational diabetes and preeclampsia [4,5]. Recently, we have reported that 47.4% of women with recurrent pregnancy losses (RPL) have vitamin D deficiency [6]. In women with RPL, decreased vitamin D level was associated with the increased prevalence of antiphospholipid antibody, antinuclear antigen antibody, anti-ssDNA, and anti-thyroperoxidase antibody. In addition, peripheral blood CD19 + B and CD56 + NK-cell levels and NK cytotoxicity were significantly higher in women with low vitamin D level when compared with those of normal vitamin D level [6]. Normal pregnancy is associated with Th2 shift in T-cell immunity [7]. The comparable shift in NK-cell immunity has been reported during normal pregnancy including a bias to NKr1 that produce IL-10 in peripheral blood, and NK3 cells that produce TGF-β in decidual NK cells [8]. Additionally, decidual innate lymphoid cell 3 (ILC3) may play a role in innate defenses, and vessel and tissue rebuilding, thus contributing to maintenance of pregnancy [9]. Contrarily, a propensity to Th1 immune response and increased NK-cell levels and cytotoxicity have been reported in women with RPL and multiple implantation failures (MIF) after in vitro fertilization and embryo transfer cycles [10]. Women with miscarriages and preeclampsia as well, have NK1 and NKT1 shift that produce high amounts of IFN-γ and little IL-4 in peripheral blood [11]. Therefore, cellular immune-regulation including innate immunity is critical for human reproduction.Women with RPL and MIF have significantly higher NK-cell levels and cytotoxicity, and dysregulated cytokine production patterns as compared to normal controls [10,12]. Activating receptor expression on NK cells was significantly increased, while inhibitory receptor expression was significantly decreased in ...

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“…Além disso, as mulheres grávidas com baixos níveis séricos de 25[OH]D podem apresentar maior risco de vaginose bacteriana, mas não a parto por cesariana 42,45 . Estudo conduzido por Ota et al (2014), mostrou que as mulheres com baixo nível de VD aumentaram significativamente as probabilidades de anormalidades autoimunes, que é um fator de risco para falência reprodutiva. A citotoxicidade das células NK e a polarização Th1 foram significativamente reduzidas in vitro pela VD, e a secreção e a polarização reduzidas da VD em células NK.…”

Section: Desfechos Materno-fetaisunclassified

“…Portanto, esses resultados levantam a possibilidade de que a VD possa estar disponível como uma nova opção terapêutica para falhas reprodutivas. É necessário um estudo mais aprofundado para elucidar o papel imuno-regulador da VD e se a administração suplementar de VD pode prevenir o aparecimento da perda de gravidez 47 . As concentrações de VD estão associadas ao peso ao nascer 37 56 .…”

Section: Desfechos Materno-fetaisunclassified

Implicações maternas e fetais da hipovitaminose D no período gestacional: uma revisão de literatura

Querido¹,

Moraes²,

Venturoso³

et al. 2017

Rev Pat Tocantins

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A vitamina D (VD) é uma vitamina lipossolúvel com fundamental desempenho em diversas funções fisiológicas. Suas fontes são alimentação, suplementação ou síntese na pele em resposta à exposição à luz solar. As complicações da hipovitaminose D na gestação podem afetar a mãe e o lactente , sendo que em casos mais graves levam a osteomalácia materna e raquitismo infantil. As mulheres podem apresentar alterações no período gestacional, periparto e pós-parto. Já em crianças, as complicações tendem a ser mais graves e afetar suas vidas por tempo mais prolongado. O objetivo desta revisão é apresentar evidências atuais da associação da hipovitaminose D gestacional e os desfechos adversos maternos e fetais. Foi realizada uma pesquisa nas bases Science Direct, PubMed e Google Scholar para publicações de janeiro de 2013 a outubro de 2017 utilizando-se combinações de palavras-chave: “vitamin D deficiency”, “pregnancy” e “prenatal care”. Em mulheres gestantes a deficiência de VD tem sido associada a pré-eclâmpsia, diabetes mellitus gestacional, vaginose bacteriana, trabalho de parto prematuro e sintomas depressivos pós-parto. Na prole, pode levar a baixo peso ao nascer e recém-nascidos para a idade gestacional, hipocalcemia neonatal, raquitismo, diabetes tipo I, cárie dentária, comprometimento de linguagem, esclerose múltipla, distúrbios neurológicos, infecções de vias aéreas superiores e asma. Portanto, a suplementação de VD é útil para evitar resultados adversos na gravidez, mas pode não ser sempre necessária, especialmente quando as recomendações de estilo de vida são boas o suficiente para preveni-las. A fim de tomar a decisão adequada sobre a suplementação com VD, cada situação clínica individual deve ser analisada e colocada no equilíbrio correto de risco e benefício antes de prescrever a suplementação de VD. Palavras-chave: Vitamina D, Deficiência de Vitamina D, Gravidez. ABSTRACT Vitamin D (VD) is a fat soluble vitamin with fundamental performance in various physiological functions. Its sources are diet, supplementation or synthesis in the skin in response to exposure to sunlight. Complications of hypovitaminosis D during pregnancy can affect the mother and infant, and in more severe cases lead to maternal osteomalacia and childhood rickets. Women may present changes during the gestational, peripartum and postpartum period. In children, complications tend to be more severe and affect their lives for a longer time. The objective of this review is to present current evidence of the association of gestational hypovitaminosis D and adverse maternal and fetal outcomes. A search was made at the bases Science Direct, PubMed and Google Scholar for publications from January 2013 to October 2017 using combinations of keywords: "vitamin D deficiency", "pregnancy" and "prenatal care". In pregnant women, VD deficiency has been associated with pre-eclampsia, gestational diabetes mellitus, bacterial vaginosis, preterm labor, and postpartum depressive symptoms. In offspring, it can lead to low birth weight and small babies for gestational age, neonatal hypocalcemia, rickets, type I diabetes, dental caries, language impairment, multiple sclerosis, neurological disorders, upper respiratory infections and asthma. Therefore, VD supplementation is useful to avoid adverse pregnancy outcomes, but may not always be necessary, especially when lifestyle recommendations are good enough to prevent them. In order to make the proper decision on VD supplementation, each individual clinical situation must be analyzed and placed in the correct balance of risk and benefit before prescribing VD supplementation. Keywords: Vitamin D, Vitamin D Deficiency, Pregnancy.

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Vitamin D deficiency may be a risk factor for recurrent pregnancy losses by increasing cellular immunity and autoimmunity

Abstract: N/A.

Cited by 170 publications

References 71 publications

Vitamin D and assisted reproduction: should vitamin D be routinely screened and repleted prior to ART? A systematic review

Vitamin D and assisted reproduction: should vitamin D be routinely screened and repleted prior to ART? A systematic review

1,25‐Dihydroxy‐vitamin D3 regulates NK‐cell cytotoxicity, cytokine secretion, and degranulation in women with recurrent pregnancy losses

Implicações maternas e fetais da hipovitaminose D no período gestacional: uma revisão de literatura

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