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      Associations of maternal vitamin D, PTH and calcium with hypertensive disorders of pregnancy and associated adverse perinatal outcomes: Findings from the Born in Bradford cohort study

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          Abstract

          Vitamin D and parathyroid hormone (PTH) regulate mineral metabolism and are required to maintain calcium levels. Vitamin D deficiency is common, particularly during pregnancy, and has been associated with hypertensive disorders of pregnancy. We sought to determine whether maternal 25(OH)D, PTH and calcium concentrations at 26 weeks gestation are associated with adverse outcomes of pregnancy and establish whether these differ by ethnicity. This study included 476 White British and 534 Pakistani origin mother-offspring pairs from the Born in Bradford cohort study. We used multinomial or logistic regression to explore the association between vitamin D, PTH and calcium with gestational hypertension (GH), pre-eclampsia (PE), caesarean section (CS), preterm birth (PTB) and small for gestational age (SGA). Pakistani women had lower 25(OH)D (median 13.0 vs 36.0 nmol/L), higher PTH (median 7.7 vs 3.3 pmol/L) and similar calcium concentrations compared to White British women. In Pakistani women, higher concentrations of 25(OH)D were associated with a 60% increased odds of GH, and a 37% reduced odds of SGA; PTH was associated with a 45% reduction in the odds of GH. In White British women, each 1 SD increase in calcium concentration was associated with a 34% increase in developing GH but a 33% reduction in the odds of PTB. Associations with PE and CS were consistent with the null. In conclusion, there are ethnic differences in the associations of 25(OH)D, PTH and calcium with important perinatal outcomes. Future research would benefit from examining the associations of 25(OH)D, PTH and calcium together with a range of perinatal outcomes in order to assess the risk-benefit action of each.

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          Baseline Serum 25-Hydroxy Vitamin D Is Predictive of Future Glycemic Status and Insulin Resistance

          OBJECTIVE—Accumulating epidemiological evidence suggests that hypovitaminosis D may be associated with type 2 diabetes and related metabolic risks. However, prospective data using the biomarker serum 25-hydroxyvitamin D [25(OH)D] are limited and therefore examined in the present study. RESEARCH DESIGN AND METHODS—A total of 524 randomly selected nondiabetic men and women, aged 40–69 years at baseline, with measurements for serum 25(OH)D and IGF-1 in the population-based Ely Study, had glycemic status (oral glucose tolerance), lipids, insulin, anthropometry, and blood pressure measured and metabolic syndrome risk (metabolic syndrome z score) derived at baseline and at 10 years of follow-up. RESULTS—Age-adjusted baseline mean serum 25(OH)D was greater in men (64.5 nmol/l [95% CI 61.2–67.9]) than women (57.2 nmol/l [54.4,60.0]) and varied with season (highest late summer). Baseline 25(OH)D was associated inversely with 10-year risk of hyperglycemia (fasting glucose: β = −0.0023, P = 0.019; 2-h glucose: β = −0.0097, P = 0.006), insulin resistance (fasting insulin β = −0.1467, P = 0.010; homeostasis model assessment of insulin resistance [HOMA-IR]: β = −0.0059, P = 0.005), and metabolic syndrome z score (β = −0.0016, P = 0.048) after adjustment for age, sex, smoking, BMI, season, and baseline value of each metabolic outcome variable. Associations with 2-h glucose, insulin, and HOMA-IR remained significant after further adjustment for IGF-1, parathyroid hormone, calcium, physical activity, and social class. CONCLUSIONS—This prospective study reports inverse associations between baseline serum 25(OH)D and future glycemia and insulin resistance. These associations are potentially important in understanding the etiology of abnormal glucose metabolism and warrant investigation in larger, specifically designed prospective studies and randomized controlled trials of supplementation.
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            Maternal vitamin D status and adverse pregnancy outcomes: a systematic review and meta-analysis.

            To estimate the associations between maternal vitamin D status and adverse pregnancy outcomes. We searched electronic databases of the human literature in PubMed, EMBASE and the Cochrane Library up to October, 2012 using the following keywords: "vitamin D" and "status" or "deficiency" or "insufficiency" and "pregnancy". A systematic review and meta-analysis were conducted on observational studies that reported the association between maternal blood vitamin D levels and adverse pregnancy outcomes including preeclampsia, gestational diabetes mellitus (GDM), preterm birth or small-for-gestational age (SGA). Twenty-four studies met the inclusion criteria. Women with circulating 25-hydroxyvitamin D [25(OH)D] level less than 50 nmol/l in pregnancy experienced an increased risk of preeclampsia [odds ratio (OR) 2.09 (95% confidence intervals 1.50-2.90)], GDM [OR 1.38 (1.12-1.70)], preterm birth [OR 1.58 (1.08-2.31)] and SGA [OR 1.52 (1.08-2.15)]. Low maternal vitamin D levels in pregnancy may be associated with an increased risk of preeclampsia, GDM, preterm birth and SGA.
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              Maternal early pregnancy vitamin D status in relation to fetal and neonatal growth: results of the multi-ethnic Amsterdam Born Children and their Development cohort.

              Low vitamin D levels during pregnancy may account for reduced fetal growth and for altered neonatal development. The present study explored the association between maternal vitamin D status measured early in pregnancy and birth weight, prevalence of small-for-gestational-age (SGA) infants and postnatal growth (weight and length), as well as the potential role of vitamin D status in explaining ethnic disparities in these outcomes. Data were derived from a large multi-ethnic cohort in The Netherlands (Amsterdam Born Children and their Development (ABCD) cohort), and included 3730 women with live-born singleton term deliveries. Maternal serum vitamin D was measured during early pregnancy (median 13 weeks, interquartile range: 12-14), and was labelled 'deficient' ( or= 50 nmol/l). Six ethnic groups were distinguished: Dutch, Surinamese, Turkish, Moroccan, other non-Western and other Western. Associations with neonatal outcomes were analysed using multivariate regression analyses. Results showed that compared with women with adequate vitamin D levels, women with deficient vitamin D levels had infants with lower birth weights ( - 114.4 g, 95 % CI - 151.2, - 77.6) and a higher risk of SGA (OR 2.4, 95 % CI 1.9, 3.2). Neonates born to mothers with a deficient vitamin D status showed accelerated growth in weight and length during the first year of life. Although a deficient vitamin D status influenced birth weight, SGA risk and neonatal growth, it played a limited role in explaining ethnic differences. Although vitamin D supplementation might be beneficial to those at risk of a deficient vitamin D status, more research is needed before a nationwide policy on the subject can be justified.
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                Author and article information

                Contributors
                gillian.santorelli@bthft.nhs.uk
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                4 February 2019
                4 February 2019
                2019
                : 9
                : 1205
                Affiliations
                [1 ]ISNI 0000 0004 0391 9047, GRID grid.418447.a, Bradford Institute for Health Research, , Temple Bank House, Bradford Royal Infirmary, ; Bradford, BD9 6RJ UK
                [2 ]ISNI 0000 0004 0391 9047, GRID grid.418447.a, Department of Diabetes and Endocrinology, , Bradford Royal Infirmary, ; Bradford, BD9 6RJ UK
                [3 ]ISNI 0000 0004 1936 7603, GRID grid.5337.2, MRC Integrated Epidemiology Unit at the University of Bristol, ; Rm OS11, Oakfield House, Oakfield Grove, Bristol, BS8 2BN UK
                [4 ]Bristol NIHR Biomedical Research Centre, Bristol, UK
                Author information
                http://orcid.org/0000-0003-0427-1783
                http://orcid.org/0000-0002-5770-8363
                Article
                37600
                10.1038/s41598-018-37600-9
                6362043
                30718630
                fb0bbf23-9e59-4bb0-94b3-515cf016f1e8
                © The Author(s) 2019

                Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 17 May 2018
                : 10 December 2018
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