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      Magnesium supplementation and preeclampsia in low-income pregnant women – a randomized double-blind clinical trial

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          Abstract

          Background

          Preeclampsia is the major cause of maternal morbidity and mortality in developing countries. Magnesium sulfate is considered first-line therapy against eclampsia and magnesium deficiency in pregnancy has been associated with unfavourable perinatal outcomes. However there are doubts if magnesium supplementation during pregnancy can previne preeclampsia especially in population with high nutritional risk. This trial aims to verify the effect of oral magnesium supplmentation on preeclampsia incidence in low income pregnant women.

          Methods

          This randomized, double-blind, placebo-controlled trial investigated the effect of oral magnesium citrate supplementation for preeclampsia in low-income Brazilian pregnant women, i.e. annual per capita income of US$ 1025 or less. Participants were admitted to the study with gestational age between 12 and 20 weeks. Magnesium serum level was measured pre-randomization and participants with hypermagnesemia were excluded. After randomizationg participants received magnesium citrate capsule (300 mg magnesium citrate) or a daily placebo capsule, until delivery. Intent-to-treat analysis was performed.

          Results

          A total of 416 pregnant women were screened and 318 enrolled according to the inclusion criteria; 159 for each arm. Twenty-eight pregnant women were lost to follow-up. 55/290 (18.9%) of pregnant women developed preeclampsia; 26/143 (18.1%) in magnesium group and 29/147 (19.7%) in the control group; OR 0.90 (CI 95% 0.48–1.69), p = 0.747. No cases of eclampsia were registered.

          Conclusion

          Oral magnesium supplementation did not reduce preeclampsia incidence in low-income and low-risk pregnant women.

          Trial registration

          Registered at ClinicalTrials.gov (Identifier NCT02032186), December 19, 2013.

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          Most cited references19

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          Maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the Caribbean.

          L Duley (1992)
          To present estimates of maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the Caribbean, and to discuss strategies to prevent these deaths. Retrospective review of all available data. Database of the World Health Organization's Maternal Health and Safe Motherhood Programme. Estimates of the total maternal mortality and the proportions of deaths associated with hypertensive disorders of pregnancy. Estimates of mortality associated with hypertensive disorders of pregnancy were similar in Africa, Latin America and the Caribbean, despite considerably higher total mortality in Africa. Variations in both overall mortality and that associated with hypertensive disorders of pregnancy were greatest in Asia. Despite their limitations, these data suggest that between 10-15% of maternal deaths are associated with hypertensive disorders of pregnancy, and that 10% are associated with eclampsia. Where maternal mortality is relatively high, the excess is likely to be due to a high mortality associated with haemorrhage and infection and reductions are most likely to come from reductions in these deaths. Evidence from both developed and developing countries suggests that deaths associated with hypertensive disorders of pregnancy are the most difficult to prevent. More rigorous assessment of interventions designed to prevent these deaths is urgently required.
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            The association between dietary factors and gestational hypertension and pre-eclampsia: a systematic review and meta-analysis of observational studies

            Background Dietary factors have been suggested to play a role in the prevention of hypertensive disorders of pregnancy (HDP), including gestational hypertension and pre-eclampsia, but inconsistent findings have been reported. A systematic review and meta-analyses were performed to synthesize evidence from observational studies of reproductive-aged women on the association between dietary factors and HDP. Methods MEDLINE and EMBASE were searched to identify studies published until the end of May 2014. Studies were included if they were observational studies of reproductive-age women and reported results on dietary factors (energy, nutrients, foods or overall dietary patterns, alone or in combination with dietary supplements) and gestational hypertension and/or pre-eclampsia. Studies were excluded if they reported on supplements not in combination with dietary intake, or examined a biomarker of dietary intake. Random effects meta-analyses were performed on calculated weighted mean differences (WMD) of dietary intake between cases and non-cases, and effect estimates were pooled. Results In total, 23 cohort and 15 case–control studies were identified for systematic review, of which 16 could be included in the meta-analyses. Based on meta-analyses of cohort studies, unadjusted energy intake was higher for pre-eclampsia cases (WMD 46 kcal/day, 95% confidence interval (CI) −13.80 to 106.23; I 2 = 23.9%, P = 0.26), although this was not statistically significant. Unadjusted intakes of magnesium (WMD 8 mg/day, 95% CI −13.99 to −1.38; I 2 = 0.0%, P = 0.41) and calcium (WMD 44 mg/day, 95% CI −84.31 to −3.62, I 2 = 51.1%, P = 0.03) were lower for the HDP cases, compared with pregnant women without HDP. Higher calcium intake consistently showed lower odds for HDP after adjustment for confounding factors (OR = 0.76, 95% CI 0.57 to 1.01, I 2 = 0.0%, P = 0.79). A few studies examining foods and dietary patterns suggested a beneficial effect of a diet rich in fruit and vegetables on pre-eclampsia, although not all the results were statistically significant. Conclusions Based on a limited number of studies, higher total energy and lower magnesium and calcium intake measured during pregnancy were identified as related to HDP. Further prospective studies are required to provide an evidence base for development of preventive health strategies, particularly focusing on dietary factors during pre-pregnancy and early pregnancy. Please see related article: http://www.biomedcentral.com/1741-7015/12/176/abstract. Electronic supplementary material The online version of this article (doi:10.1186/s12916-014-0157-7) contains supplementary material, which is available to authorized users.
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              Magnesium supplementation in pregnancy.

              Magnesium is an essential mineral required for regulation of body temperature, nucleic acid and protein synthesis and in maintaining nerve and muscle cell electrical potentials. Many women, especially those from disadvantaged backgrounds, have low intakes of magnesium. Magnesium supplementation during pregnancy may be able to reduce fetal growth restriction and pre-eclampsia, and increase birthweight.
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                Author and article information

                Contributors
                joaoguilherme@imip.org.br
                Journal
                BMC Pregnancy Childbirth
                BMC Pregnancy Childbirth
                BMC Pregnancy and Childbirth
                BioMed Central (London )
                1471-2393
                9 April 2020
                9 April 2020
                2020
                : 20
                : 208
                Affiliations
                [1 ]GRID grid.419095.0, ISNI 0000 0004 0417 6556, Department of Pediatrics, , Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), ; Rua dos Coelhos, 300, Boa Vista, Recife, Pernambuco CEP: 50070-550 Brazil
                [2 ]Mother and Child Health, Faculdade Pernambucana de Saúde (FPS), Av. Mal. Mascarenhas de Morais, 4861, Imbiribeira, Recife, Pernambuco CEP: 51150-000 Brazil
                [3 ]Department of Pediatrics, Hospital Dom Malan, R Joaquim Nabuco, S/N, Centro, Petrolina, Pernambuco CEP: 56304-900 Brazil
                Article
                2877
                10.1186/s12884-020-02877-0
                7146998
                32272914
                b8194267-4646-4a65-956b-af30b485703a
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 4 December 2019
                : 16 March 2020
                Funding
                Funded by: FundRef http://data.crossref.org/fundingdata/funder/10.13039/100000865, Bill & Melinda Gates Foundation;
                Award ID: OPP1107597
                Funded by: CNPq
                Award ID: 43998620168
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Obstetrics & Gynecology
                pregnancy,preeclampsia,oral magnesium
                Obstetrics & Gynecology
                pregnancy, preeclampsia, oral magnesium

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