Maternal Vitamin D Status and Risk of Pre-Eclampsia: A Systematic Review and Meta-Analysis

Food Security Research Center (Marj.T., A.S.-A., Mary.T., A.E.), and Department of Community Nutrition, School of Nutrition and Food Science (Marj.T., A.S.-A., A.E.), Isfahan University of Medical Sciences, Isfahan 81745, Iran.
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 06/2013; 98(8). DOI: 10.1210/jc.2013-1257
Source: PubMed


Although several studies have investigated the association between maternal serum vitamin D levels and risk of pre-eclampsia, findings are inconsistent. This systematic review and meta-analysis of published observational studies was conducted to summarize the evidence on the association between maternal serum vitamin D levels and risk of pre-eclampsia.

PubMed, ISI (Web of science), SCOPUS, SCIRUS, Google Scholar, and EMBASE databases were searched to identify related articles published through December 2012. For systematic review, we found 15 articles that assessed the association between maternal serum vitamin D levels and risk of pre-eclampsia. The meta-analysis was done on 8 studies that reported odds ratios or relative risks for pre-eclampsia. Between-study heterogeneity was examined using Cochran's Q test and I(2). Subgroup analysis and meta-regression were used to find possible sources of heterogeneity.

The meta-analysis on 8 relevant papers revealed an overall significant association between vitamin D deficiency and risk of pre-eclampsia; however, there was significant between-study heterogeneity (I(2) = 52.7%; P = .039). In the subgroup analysis, we found that the overall effect was significant for studies that defined vitamin D deficiency as 25(OH)D ≤ 50 nmol/L (20 ng/mL), but not for those that considered it as <38 nmol/L (15.2 ng/mL). The association was seen for "cohort or nested case-control studies" as well as for "cross-sectional or case-control studies" (2.78; 1.45-5.33; P = .002). When the analysis was done by study location, the associations remained significant only for studies that came from the United States.

There was a significant relationship between vitamin D deficiency and increased risk of pre-eclampsia. Further studies are required, particularly in developing countries.

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    • "concentrations. Vitamin D may also be implicated in the development of the second stage of pre-eclampsia pathophysiology as vitamin D deficient rodents display endothelial vasodilator dysfunction and hypertension [27] [28] although data from human studies are conflicting [29] [30]. "
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    ABSTRACT: Introduction: Incomplete human extravillous trophoblast (EVT) invasion of the decidua and maternal spiral arteries is characteristic of pre-eclampsia, a condition linked to low maternal vitamin D status. It is hypothesized that dysregulated vitamin D action in uteroplacental tissues disrupts EVT invasion leading to malplacentation. Methods: This study assessed the effects of the active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25-D3), and its precursor, 25-hydroxyvitamin D3 (25-D3), on primary human EVT isolated from first trimester pregnancies. Expression of EVT markers (cytokeratin-7, HLA-G), the vitamin D-activating enzyme (CYP27B1) and 1,25-D3 receptor (VDR) was assessed by immunocytochemistry. EVT responses following in vitro treatment with 1,25-D3 (0-10 nM) or 25-D3 (0-100 nM) for 48-60 h were assessed using quantitative RT-PCR (qRT-PCR) analysis of key target genes. Effects on EVT invasion through Matrigel(®) were quantified alongside zymographic analysis of secreted matrix metalloproteinases (MMPs). Effects on cell viability were assessed by measurement of MTT. Results: EVT co-expressed mRNA and protein for CYP27B1 and VDR, and demonstrated induction of mRNA encoding vitamin D-responsive genes, 24-hydroxylase (CYP24A1) and cathelicidin following 1,25-D3 treatment. EVT could respond to 1,25-D3 and 25-D3, both of which significantly increased EVT invasion, with maximal effect at 1 nM 1,25-D3 (1.9-fold; p < 0.01) and 100 nM 25-D3 (2.2-fold; p < 0.05) respectively compared with untreated controls. This was accompanied by increased pro-MMP2 and pro-MMP9 secretion. The invasion was independent of cell viability, which remained unchanged. Discussion: These data support a role for vitamin D in EVT invasion during human placentation and suggest that vitamin D-deficiency may contribute to impaired EVT invasion and pre-eclampsia.
    Placenta 01/2015; 36(4). DOI:10.1016/j.placenta.2014.12.021 · 2.71 Impact Factor
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    • "It poses a threat to maternal and fetal health and often results in premature delivery of the child. The development of preeclampsia is linked to altered vitamin D metabolism [2], and might be a result from placental dysfunction [24]. However, the underlying cause of the development of preeclampsia remains elusive. "
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    ABSTRACT: Preeclampsia, a hypertensive disorder in pregnancy develops in 2–8% of pregnancies worldwide. Winter season and vitamin D deficiency have been associated with its onset.ObjectiveTo investigate the influence of season on maternal vitamin D status and placental vitamin D metabolism.Methods25-OH vitamin D and 1,25-(OH)2 vitamin D were measured in maternal serum obtained during the winter or summer months from 63 pregnant women at delivery (43 healthy, 20 preeclampsia). In a subgroup, mRNA expression of CYP24A1 (24-hydroxylase), CYP27B1 (1α-hydroxylase) and VDR (vitamin D receptor) were quantified by real time PCR in placental samples of 14 women with normal pregnancies and 13 with preeclampsia.ResultsIn patients with preeclampsia,25-OH vitamin D levels were lower, but differed significantly from controls only in summer (18.21±17.1 vs 49.2±29.2 ng/mL, P<0.001), whereas 1,25-(OH)2 vitamin D levels were significantly lower only in winter (291±217 vs 612.3±455 pmol/mL, P<0.05). A two-factorial analysis of variance produced a statistically significant model (P<0.0001) with an effect of season (P<0.01) and preeclampsia (P = 0.01) on maternal 25-OH vitamin D levels, as well as a significant interaction between the two variables (P = 0.02). Placental gene expression of CYP24A1, CYP27B1, and VDR did not differ between groups or seasons. A negative correlation between placental gene expression of CYP24A1 and CYP27B1 was observed only in healthy controls (r = −0.81, P<0.0001).SummaryPatients with preeclampsia displayed lower vitamin D serum levels in response to seasonal changes.The regulation of placental CYP24A1, but not of the VDR or CYP27B1 might be altered in preeclampsia.
    PLoS ONE 08/2014; 9(8):e105558. DOI:10.1371/journal.pone.0105558 · 3.23 Impact Factor
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    • "Vitamin D deficiency is increasingly recognized as a health problem across the world and is particularly prevalent also in pregnant women [44]. Vitamin D deficiency has been associated with higher rates of pregnancy complications, for example, pre-eclampsia [45] [46]. This makes sense, as vitamin D positively acts on endothelial function [47] and might therefore be beneficial in preventing hypertensive disorders in pregnancy going along with an endothelial pathology as well as in preserving transplant functions. "
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    ABSTRACT: In this article, we focus on the biggest groups of organ transplant recipients, patients with a kidney or liver graft. Among these patients, about one sixth included women of childbearing potential. Therefore, the wish of getting pregnant is frequent in these peculiar patients, and careful planning and management of the pregnancies requires the expertise of obstetricians, midwives and transplant experts. Altogether, the outcome of the pregnancies in these women is acceptable. About 75% off all pregnancies ended successfully with live births, and this is comparable if not superior to pregnancies in healthy women. This success might be caused not only by the special and intensive care provided to these high-risk pregnancies by the transplant centres but also by the low rate of unplanned pregnancies. The risk of rejections and organ loss after delivery is about 10%, and it is slightly enhanced in liver transplant recipients (LTRs) in comparison to kidney graft recipients (KTRs) but the number of organ losses in direct association with a pregnancy is rare. However, there is not only a higher frequency of pregnancy-associated disorders such as pre-eclampsia and preterm delivery but also an acceleration of hypertension, new-onset diabetes mellitus and newly arising infections also favoured by the maintained immunosuppressive therapy. This implies a specialized 'control system' for these pregnant women that comprises ultrasound and Doppler investigation for risk assessment, infection screening, suitable therapy and the choice of non-teratogenic immunosuppressives. Antihypertensive treatment must be well balanced and adjusted to the possible growth-retarding effect on the foetus as well as on the co-morbidity of the mother. Finally, supplementation of vitamin D and iron is much more important in these transplanted women than in healthy pregnant women as vitamin D deficiency and anaemia are discussed to have an impact on pre-eclampsia and preterm delivery. These claims are widely discussed. Furthermore, the current literature is systematically reviewed by Scopus analysis.
    Bailli&egrave re s Best Practice and Research in Clinical Obstetrics and Gynaecology 08/2014; 28(8). DOI:10.1016/j.bpobgyn.2014.07.021 · 1.92 Impact Factor
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