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      Blood pressure in 3-year-old girls associates inversely with umbilical cord serum 25-hydroxyvitamin D: an Odense Child Cohort study

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          Abstract

          Background

          Low foetal vitamin D status may be associated with higher blood pressure (BP) in later life.

          Objective

          To examine whether serum 25-hydroxyvitamin D 2+3 (s-25OHD) in cord and pregnancy associates with systolic and diastolic BP (SBP; DBP) in children up to 3 years of age.

          Design

          Prospective, population-based cohort study.

          Methods

          We included 1594 singletons from the Odense Child Cohort with available cord s-25OHD and BP data at median age 3.7 months (48% girls), 18.9 months (44% girls) or 3 years (48% girls). Maternal s-25OHD was also assessed at gestational ages 12 and 29 weeks. Multiple regression models were stratified by sex a priori and adjusted for maternal educational level, season of birth and child height, weight and age.

          Results

          In 3-year-old girls, SBP decreased with −0.7 mmHg (95% CI −1.1; −0.3, P = 0.001) and DBP with −0.4 mmHg (95% CI −0.7; −0.1, P = 0.016) for every 10 nmol/L increase in cord s-25OHD in adjusted analyses. Moreover, the adjusted odds of having SBP >90th percentile were reduced by 30% for every 10 nmol/L increase in cord s-25OHD ( P = 0.004) and by 64% for cord s-25OHD above the median 45.1 nmol/L ( P = 0.02). Similar findings were observed between pregnancy s-25OHD and 3-year SBP, cord s-25OHD and SBP at 18.9 months, and cord s-25OHD and DBP at 3 years. No consistent associations were observed between s-25OHD and BP in boys.

          Conclusion

          Cord s-25OHD was inversely associated with SBP and DBP in young girls, but not in boys. Higher vitamin D status in foetal life may modulate BP in young girls. The sex difference remains unexplained.

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          Most cited references21

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          Maternal vitamin D status during pregnancy and child outcomes.

          To investigate whether exposure to high maternal concentrations of 25(OH)-vitamin D in pregnancy poses any risk to the child. Prospective study. Princess Anne Maternity Hospital, Southampton, UK. A group of 596 pregnant women were recruited. A total of 466 (78%) children were examined at birth, 440 (74%) at age 9 months and 178 (30%) at age 9 years. Maternal 25 (OH)-vitamin D concentrations were measured in late pregnancy. Anthropometry of the child was recorded at birth, 9 months and 9 years. At 9 months, atopic eczema was assessed. At 9 years, children had an echocardiogram and a dual energy x-ray absorptiometry scan, blood pressure, arterial compliance and carotid intima-media thickness were measured and intelligence and psychological function assessed. There were no associations between maternal 25(OH)-vitamin D concentrations and the child's body size or measures of the child's intelligence, psychological health or cardiovascular system. Children whose mothers had a 25(OH)-vitamin D concentration in pregnancy >75 nmol/l had an increased risk of eczema on examination at 9 months (OR 3.26, 95% CI 1.15-9.29, P=0.025) and asthma at age 9 years (OR 5.40, 95% CI, 1.09-26.65, P=0.038) compared to children whose mothers had a concentration of <30 nmol/l. Exposure to maternal concentrations of 25(OH)-vitamin D in pregnancy in excess of 75 nmol/l does not appear to influence the child's intelligence, psychological health or cardiovascular system; there could be an increased risk of atopic disorders, but this needs confirmation in other studies.
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            Vitamin D supplementation in pregnancy: a systematic review.

            It is unclear whether or not the current evidence base allows definite conclusions to be made regarding the optimal maternal circulating concentration of 25-hydroxyvitamin D [25(OH)D] during pregnancy, and how this might best be achieved. To answer the following questions: (1) What are the clinical criteria for vitamin D deficiency in pregnant women? (2) What adverse maternal and neonatal health outcomes are associated with low maternal circulating 25(OH)D? (3) Does maternal supplementation with vitamin D in pregnancy lead to an improvement in these outcomes (including assessment of compliance and effectiveness)? (4) What is the optimal type (D2 or D3), dose, regimen and route for vitamin D supplementation in pregnancy? (5) Is supplementation with vitamin D in pregnancy likely to be cost-effective? We performed a systematic review and where possible combined study results using meta-analysis to estimate the combined effect size. Major electronic databases [including Database of Abstracts of Reviews of Effects (DARE), Centre for Reviews and Dissemination (CRD), Cochrane Database of Systematic Reviews (CDSR) and the Health Technology Assessment (HTA) database] were searched from inception up to June 2012 covering both published and grey literature. Bibliographies of selected papers were hand-searched for additional references. Relevant authors were contacted for any unpublished findings and additional data if necessary. Abstracts were reviewed by two reviewers. pregnant women or pregnant women and their offspring. either assessment of vitamin D status [dietary intake, sunlight exposure, circulating 25(OH)D concentration] or supplementation of participants with vitamin D or food containing vitamin D (e.g. oily fish). offspring - birthweight, birth length, head circumference, bone mass, anthropometry and body composition, risk of asthma and atopy, small for gestational dates, preterm birth, type 1 diabetes mellitus, low birthweight, serum calcium concentration, blood pressure and rickets; mother - pre-eclampsia, gestational diabetes mellitus, risk of caesarean section and bacterial vaginosis. Seventy-six studies were included. There was considerable heterogeneity between the studies and for most outcomes there was conflicting evidence. The evidence base was insufficient to reliably answer question 1 in relation to biochemical or disease outcomes. For questions 2 and 3, modest positive relationships were identified between maternal 25(OH)D and (1) offspring birthweight in meta-analysis of three observational studies using log-transformed 25(OH)D concentrations after adjustment for potential confounding factors [pooled regression coefficient 5.63 g/10% change maternal 25(OH)D, 95% confidence interval (CI) 1.11 to 10.16 g], but not in those four studies using natural units, or across intervention studies; (2) offspring cord blood or postnatal calcium concentrations in a meta-analysis of six intervention studies (all found to be at high risk of bias; mean difference 0.05 mmol/l, 95% CI 0.02 to 0.05 mmol/l); and (3) offspring bone mass in observational studies judged to be of good quality, but which did not permit meta-analysis. The evidence base was insufficient to reliably answer questions 4 and 5. Study methodology varied widely in terms of study design, population used, vitamin D status assessment, exposure measured and outcome definition. The evidence base is currently insufficient to support definite clinical recommendations regarding vitamin D supplementation in pregnancy. Although there is modest evidence to support a relationship between maternal 25(OH)D status and offspring birthweight, bone mass and serum calcium concentrations, these findings were limited by their observational nature (birthweight, bone mass) or risk of bias and low quality (calcium concentrations). High-quality randomised trials are now required. This study is registered as PROSPERO CRD42011001426. The National Institute for Health Research Health Technology Assessment programme.
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              Vitamin D and risk of future hypertension: meta-analysis of 283,537 participants.

              The evidence on the association between baseline vitamin D status and risk of incident hypertension in general populations is limited and has not been reliably quantified. We conducted a systematic review and meta-analysis of published prospective studies evaluating the associations of baseline vitamin D status (circulating 25-hydroxyvitamin D [25(OH)D] levels and dietary vitamin D intake) with risk of hypertension. Eligible studies were identified in a literature search of MEDLINE, EMBASE, and Web of Science up to November 2012. Pooled relative risks (RRs) with 95% confidence intervals were calculated using random effects models. Generalized least-squares trend estimation was used to assess dose-response relationships. Of the 2,432 articles reviewed for eligibility, eight unique prospective cohorts with aggregate data on 283,537 non-overlapping participants and 55,816 incident hypertension cases were included. The RRs (95% CIs) for hypertension in a comparison of extreme thirds of baseline levels of vitamin D were 0.70 (0.58, 0.86) for seven studies that measured blood 25(OH) D levels and 1.00 (0.95, 1.05) for four studies that assessed dietary vitamin D intake. The pooled RR of incident hypertension per 10 ng/mL increment in baseline 25(OH)D levels was 0.88 (0.81, 0.97) in dose-response analysis. Evidence was lacking of heterogeneity among studies that measured blood 25(OH) D levels and those that assessed dietary vitamin D status. Studies are needed to determine whether the association of vitamin D with hypertension represents a causal association and also to determine whether vitamin D therapy may be beneficial in the prevention or the treatment of hypertension.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                December 2018
                04 October 2018
                : 7
                : 12
                : 1236-1244
                Affiliations
                [1 ]Department of Clinical Research , Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
                [2 ]Department of Public Health , Environmental Medicine, University of Southern Denmark, Odense, Denmark
                [3 ]Hans Christian Andersen Children’s Hospital , Odense University Hospital, Odense, Denmark
                [4 ]Department of Obstetrics and Gynecology , Herlev Hospital, Copenhagen, Denmark
                [5 ]Department of Medical Endocrinology , Odense University Hospital, Odense, Denmark
                Author notes
                Correspondence should be addressed to M Andersen: Marianne.andersen1@ 123456rsyd.dk
                Article
                EC-18-0308
                10.1530/EC-18-0308
                6240151
                30352408
                237516b7-b6f7-4b9e-bc6a-12d5f792971d
                © 2018 The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 26 September 2018
                : 04 October 2018
                Categories
                Research

                vitamin d,blood pressure,sex-dimorphism,children
                vitamin d, blood pressure, sex-dimorphism, children

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