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      Calcium and Vitamin D Supplementation for Prevention of Preeclampsia: A Systematic Review and Network Meta-Analysis

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          Abstract

          Vitamin D supplementation effects with or without calcium in pregnancy for reducing risk of preeclampsia and gestational or pregnancy induced hypertension are controversial. Literature was systematically searched in Medline, Scopus and Cochrane databases from inception to July 2017. Only randomized controlled trials (RCTs) in English were selected if they had any pair of interventions (calcium, vitamin D, both, or placebo). Systematic review with two-step network-meta-analysis was used to indirectly estimate supplementary effects. Twenty-seven RCTs with 28,000 women were eligible. A direct meta-analysis suggested that calcium, vitamin D, and calcium plus vitamin D could lower risk of preeclampsia when compared to placebo with the pooled risk ratios (RRs) of 0.54 (0.41, 0.70), 0.47 (0.24, 0.89) and 0.50 (0.32, 0.78), respectively. Results of network meta-analysis were similar with the corresponding RRs of 0.49 (0.35, 0.69), 0.43 (0.17, 1.11), and 0.57 (0.30, 1.10), respectively. None of the controls were significant. Efficacy of supplementation, which was ranked by surface under cumulative ranking probabilities, were: vitamin D (47.4%), calcium (31.6%) and calcium plus vitamin D (19.6%), respectively. Calcium supplementation may be used for prevention for preeclampsia. Vitamin D might also worked well but further large scale RCTs are warranted to confirm our findings.

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          Global and regional estimates of preeclampsia and eclampsia: a systematic review.

          Reduction of maternal mortality is a target within the Millennium Development Goals. Data on the incidence of preeclampsia and eclampsia, one of the main causes of maternal deaths, are required at both national and regional levels to inform policies. We conducted a systematic review of the incidence of hypertensive disorders of pregnancy (HDP) with the objective of evaluating its magnitude globally and in different regions and settings. We selected studies using pre-specified criteria, recorded database characteristics and assessed methodological quality of the eligible studies reporting incidence of any HDP during the period 2002-2010. A logistic model was then developed to estimate the global and regional incidence of HDP using pre-specified predictor variables where empiric data were not available. We found 129 studies meeting the inclusion criteria, from which 74 reports with 78 datasets reporting HDP were analysed. This represents nearly 39 million women from 40 countries. When the model was applied, the overall estimates are 4.6% (95% uncertainty range 2.7-8.2), and 1.4% (95% uncertainty range 1.0-2.0) of all deliveries for preeclampsia and eclampsia respectively, with a wide variation across regions. The figures we obtained give a general idea of the magnitude of the problem and suggest that some regional variations might exist. The absence of data in many countries is of concern, however, and efforts should be made to implement data collection and reporting for substantial statistics. The implementation of large scale surveys conducted during a short period of time could provide more reliable and up-to-date estimations to inform policy. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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            The two stage model of preeclampsia: variations on the theme.

            The Two Stage Model of preeclampsia proposes that a poorly perfused placenta (Stage 1) produces factor(s) leading to the clinical manifestations of preeclampsia (Stage 2). Stage 1 is not sufficient to cause the maternal syndrome but interacts with maternal constitutional factors (genetic, behavioral or environmental) to result in Stage 2. Recent information indicates the necessity for modifications of this model. It is apparent that changes relevant to preeclampsia and other implantation disorders can be detected in the first trimester, long before the failed vascular remodeling necessary to reduce placental perfusion is completed. In addition, although the factor(s) released from the placenta has usually been considered a toxin, we suggest that what is released may also be an appropriate signal from the fetal/placental unit to overcome reduced nutrient availability that cannot be tolerated by some women who develop preeclampsia. Further, it is evident that linkage is not likely to be one factor but several, different for different women. Also although the initial model limited the role of maternal constitutional factors to the genesis of Stage 2, this does not appear to be the case. It is evident that the factors increasing risk for preeclampsia are also associated with abnormal implantation. These several modifications have important implications. An earlier origin for Stage 1, which appears to be recognizable by altered concentrations of placental products, could allow earlier intervention. The possibility of a fetal placental factor increasing nutrient availability could provide novel therapeutic options. Different linkages and preeclampsia subtypes could direct specific preventive treatments for different women while the role of maternal constitutional factors to affect placentation provides targets for prepregnancy therapy. The modified Two Stage Model provides a useful guide towards investigating pathophysiology and guiding therapy.
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              Pre-eclampsia, eclampsia and adverse maternal and perinatal outcomes: a secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health.

              To assess the incidence of hypertensive disorders of pregnancy and related severe complications, identify other associated factors and compare maternal and perinatal outcomes in women with and without these conditions. Secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health (WHOMCS) database. Cross-sectional study implemented at 357 health facilities conducting 1000 or more deliveries annually in 29 countries from Africa, Asia, Latin America and the Middle East. All women suffering from any hypertensive disorder during pregnancy, the intrapartum or early postpartum period in the participating hospitals during the study period. We calculated the proportion of the pre-specified outcomes in the study population and their distribution according to hypertensive disorders' severity. We estimated the association between them and maternal deaths, near-miss cases, and severe maternal complications using a multilevel logit model. Hypertensive disorders of pregnancy. Potentially life-threatening conditions among maternal near-miss cases, maternal deaths and cases without severe maternal outcomes. Overall, 8542 (2.73%) women suffered from hypertensive disorders. Incidences of pre-eclampsia, eclampsia and chronic hypertension were 2.16%, 0.28% and 0.29%, respectively. Maternal near-miss cases were eight times more frequent in women with pre-eclampsia, and increased to up to 60 times more frequent in women with eclampsia, when compared with women without these conditions. The analysis of this large database provides estimates of the global distribution of the incidence of hypertensive disorders of pregnancy. The information on the most frequent complications related to pre-eclampsia and eclampsia could be of interest to inform policies for health systems organisation. © 2014 RCOG The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                18 October 2017
                October 2017
                : 9
                : 10
                : 1141
                Affiliations
                [1 ]Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 RAMA VI Road, Rachathevi, Bangkok 10400, Thailand; dr.winkhaing@ 123456gmail.com (W.K.); sasivimol.rat@ 123456mahidol.ac.th (S.R.); ammarin.tha@ 123456mahidol.ac.th (A.T.)
                [2 ]Department of Preventive and Social Medicine, University of Medicine, Mandalay 100102, Myanmar
                [3 ]Sleep Disorder Center, Division of Pulmonary and Critical Care, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand; vtantrakul@ 123456gmail.com
                [4 ]Department of Obstetrics and Gynecology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand; orawinra38@ 123456gmail.com
                [5 ]School of Medicine and Public Health, Faculty of Health and Medicine, The University of Newcastle, Callaghan, NSW 2308, Australia; mark.mcevoy@ 123456newcastle.edu.au (M.M.); john.attia@ 123456newcastle.edu.au (J.A.)
                Author notes
                [* ]Correspondence: dr.sakda@ 123456gmail.com ; Tel.: +66-2-201-1269
                Article
                nutrients-09-01141
                10.3390/nu9101141
                5691757
                29057843
                28435b43-2f20-4640-bba8-a5079c4a553d
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 September 2017
                : 13 October 2017
                Categories
                Review

                Nutrition & Dietetics
                calcium,network meta-analysis,gestational hypertension,preeclampsia,prevention,systematic review,vitamin d

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