Evidence-based policy on dietary calcium and vitamin D

Copyright © 2011 American Society for Bone and Mineral Research.Peer reviewedPostprin

Calcium supplementation to prevent pre-eclampsia: protocol for an individual participant data meta- analysis, network meta-analysis and health economic evaluation

The UKRI Medical Research Council supports this work—Global Maternal and Neonatal Health grant number MR/T010185/1. This work is also funded by the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Sexual and Reproductive Health and Research (SRH), WHO. JPV is supported by the NHMRC Investigator grant.IntroductionLow dietary calcium intake is a risk factor for pre-eclampsia, a major contributor to maternal and perinatal mortality and morbidity worldwide. Calcium supplementation can prevent pre-eclampsia in women with low dietary calcium. However, the optimal dose and timing of calcium supplementation are not known. We plan to undertake an individual participant data (IPD) meta-analysis of randomised trials to determine the effects of various calcium supplementation regimens in preventing pre-eclampsia and its complications and rank these by effectiveness. We also aim to evaluate the cost-effectiveness of calcium supplementation to prevent pre-eclampsia.Methods and analysisWe will identify randomised trials on calcium supplementation before and during pregnancy by searching major electronic databases including Embase, CINAHL, MEDLINE, CENTRAL, PubMed, Scopus, AMED, LILACS, POPLINE, AIM, IMSEAR, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform, without language restrictions, from inception to February 2022. Primary researchers of the identified trials will be invited to join the International Calcium in Pregnancy Collaborative Network and share their IPD. We will check each study's IPD for consistency with the original authors before standardising and harmonising the data. We will perform a series of one-stage and two-stage IPD random-effect meta-analyses to obtain the summary intervention effects on pre-eclampsia with 95% CIs and summary treatment-covariate interactions (maternal risk status, dietary intake, timing of intervention, daily dose of calcium prescribed and total intake of calcium). Heterogeneity will be summarised using tau(2), I-2 and 95% prediction intervals for effect in a new study. Sensitivity analysis to explore robustness of statistical and clinical assumptions will be carried out. Minor study effects (potential publication bias) will be investigated using funnel plots. A decision analytical model for use in low-income and middle-income countries will assess the cost-effectiveness of calcium supplementation to prevent pre-eclampsia.Ethics and disseminationNo ethical approvals are required. We will store the data in a secure repository in an anonymised format. The results will be published in peer-reviewed journals.PROSPERO registration numberCRD42021231276.UKRI Medical Research Council MR/T010185/1UNDP/UNFPA/UNICEF/WHO/World BankNHMRC Investigato

Low-dose calcium supplementation for preventing pre-eclampsia: a systematic review and commentary.

BACKGROUND: Epidemiological data link low dietary calcium with pre-eclampsia. Current recommendations are for 1.5-2 g/day calcium supplementation for low-intake pregnant women, based on randomised controlled trials of ≥1 g/day calcium supplementation from 20 weeks of gestation. This is problematic logistically in low-resource settings; excessive calcium may be harmful; and 20 weeks may be too late to alter outcomes. OBJECTIVES: To review the impact of lower dose calcium supplementation on pre-eclampsia risk. SEARCH STRATEGY AND SELECTION CRITERIA: We searched PubMed and the Cochrane Pregnancy and Childbirth Group trials register. DATA COLLECTION AND ANALYSIS: Two authors extracted data from eligible randomised and quasi-randomised trials of low-dose calcium (LDC, <1 g/day), with or without other supplements. MAIN RESULTS: Pre-eclampsia was reduced consistently with LDC with or without co-supplements (nine trials, 2234 women, relative risk [RR] 0.38; 95% confidence interval [95% CI] 0.28-0.52), as well as for subgroups: LDC alone (four trials, 980 women, RR 0.36; 95% CI 0.23-0.57]); LDC plus linoleic acid (two trials, 134 women, RR 0.23; 95% CI 0.09-0.60); LDC plus vitamin D (two trials, 1060 women, RR 0.49; 0.31-0.78) and a trend for LDC plus antioxidants (one trial, 60 women, RR 0.24; 95% CI 0.06-1.01). Overall results were consistent with the single quality trial of LDC alone (171 women, RR 0.30; 95% CI 0.06-1.38). LDC plus antioxidants commencing at 8-12 weeks tended to reduce miscarriage (one trial, 60 women, RR 0.06; 95% CI 0.00-1.04). CONCLUSIONS: These limited data are consistent with LDC reducing the risk of pre-eclampsia; confirming this in sufficiently powered randomised controlled trials would have implications for current guidelines and their global implementation

Participant recruitment and retention in longitudinal preconception randomized trials: lessons learnt from the Calcium And Pre-eclampsia (CAP) trial.

BACKGROUND: The preconception period has the potential to influence pregnancy outcomes and randomized controlled trials (RCTs) are needed to evaluate a variety of potentially beneficial preconception interventions. However, RCTs commencing before pregnancy have significant participant recruitment and retention challenges. The Calcium And Pre-eclampsia trial (CAP trial) is a World Health Organization multi-country RCT of calcium supplementation commenced before pregnancy to prevent recurrent pre-eclampsia in which non-pregnant participants are recruited and followed up until childbirth. This sub-study explores recruitment methods and preconception retention of participants of the CAP trial to inform future trials. METHODS: Recruiters at the study sites in Argentina, South Africa and Zimbabwe completed post-recruitment phase questionnaires on recruitment methods used. Qualitative data from these questionnaires and quantitative data on pre-pregnancy trial visit attendance and pregnancy rates up to September 2016 are reported in this paper. RStudio (Version 0.99.903 https://www.rstudio.org ) statistical software was used for summary statistics. RESULTS: Between July 2011 and 8 September 2016, 1354 women with previous pre-eclampsia were recruited. Recruitment took 2 years longer than expected and was facilitated mainly through medical record/register and maternity ward/clinic-based strategies. Recruiters highlighted difficulties associated with inadequate medical records, redundant patient contact details, and follow-up of temporarily ineligible women as some of the challenges faced. Whilst the attendance rates at pre-pregnancy visits were high (78% or more), visits often occurred later than scheduled. Forty-five percent of participants became pregnant (614/1354), 33.5% (454/1354) within 1 year of randomization. CONCLUSIONS: In preconception trials, both retrospective and prospective methods are useful for recruiting eligible women with certain conditions. However, these are time-consuming in low-resource settings with suboptimal medical records and other challenges. Trial planners should ensure that trial budgets cover sufficient on-site researchers with pre-trial training, and should consider using mobile phone and web-based electronic tools to optimize recruitment and retention. This should lead to greater efficiency and shorter trial durations. TRIAL REGISTRATION: Pan-African Clinical Trials Registry, Registration Number: PACTR201105000267371 . The trial was registered on 6 December 2016

Vitamin D and Foot and Ankle Trauma: An individual or societal problem?

Background Vitamin D deficiency is a worldwide health concern. Hypovitaminosis D may adversely affect recovery from bone injury. The authors aimed to perform an audit of the Vitamin D status of patients in three centres in the United Kingdom presenting with foot and ankle osseous damage. Methods Serum 25-hydroxyvitamin-D (vitamin D) levels were obtained in patients presenting with imaging confirmed foot and ankle osseous trauma. Variables including age, gender, ethnicity, location, season, month, anatomical location and type of bone injury were recorded. Results 308 patients were included from three different centres. 66.6% were female. The average age was 47.7 (range; 10–85). The mean hydroxyvitamin-D levels were 52.0 nmol/L (SD 28.5). 18.8% were grossly deficient, 23.7% deficient, 34.7% insufficient and 22.7% within normal range. 351 separate bone injuries were identified of which 104 were categorised as stress reactions, 134 as stress fractures, 105 as fractures and 8 non-unions. Age, gender, anatomical location and fracture type did not statistically affect vitamin D levels. Ethnicity did affect Vitamin D levels: non-Caucasians mean levels were 32.4 nmols/L compared to Caucasian levels of 53.2 nmol/L (p = 0.0026). Conclusion Only 18.8% of our trauma patients had a normal Vitamin D level and 22.7% were grossly deficient. Patient age, gender, anatomical location and injury type did not statistically affect vitamin D levels. No difference between trauma and elective patients were found. Hypovitaminosis D is a problem of society in general rather than specific to certain foot and ankle injury patterns or particular patient groups sustaining trauma. Level of evidence 2b

Prepregnancy and early pregnancy calcium supplementation among women at high risk of pre-eclampsia : a multicentre, double-blind, randomised, placebo-controlled trial

CITATION: Hofmeyr, G. J., et al. 2019. Prepregnancy and early pregnancy calcium supplementation among women at high risk of pre-eclampsia : a multicentre, double-blind, randomised, placebo-controlled trial. The Lancet, 393(10169):P330-339, doi:10.1016/S0140-6736(18)31818-X.The original publication is available at https://www.thelancet.comBackground: Reducing deaths from hypertensive disorders of pregnancy is a global priority. Low dietary calcium might account for the high prevalence of pre-eclampsia and eclampsia in low-income countries. Calcium supplementation in the second half of pregnancy is known to reduce the serious consequences of pre-eclampsia; however, the effect of calcium supplementation during placentation is not known. We aimed to test the hypothesis that calcium supplementation before and in early pregnancy (up to 20 weeks’ gestation) prevents the development of pre-eclampsia Methods: We did a multicountry, parallel arm, double-blind, randomised, placebo-controlled trial in South Africa, Zimbabwe, and Argentina. Participants with previous pre-eclampsia and eclampsia received 500 mg calcium or placebo daily from enrolment prepregnancy until 20 weeks’ gestation. Participants were parous women whose most recent pregnancy had been complicated by pre-eclampsia or eclampsia and who were intending to become pregnant. All participants received unblinded calcium 1·5 g daily after 20 weeks’ gestation. The allocation sequence (1:1 ratio) used computer-generated random numbers in balanced blocks of variable size. The primary outcome was pre-eclampsia, defined as gestational hypertension and proteinuria. The trial is registered with the Pan-African Clinical Trials Registry, number PACTR201105000267371. The trial closed on Oct 31, 2017. Findings: Between July 12, 2011, and Sept 8, 2016, we randomly allocated 1355 women to receive calcium or placebo; 331 of 678 participants in the calcium group versus 320 of 677 in the placebo group became pregnant, and 298 of 678 versus 283 of 677 had pregnancies beyond 20 weeks’ gestation. Pre-eclampsia occurred in 69 (23%) of 296 participants in the calcium group versus 82 (29%) of 283 participants in the placebo group with pregnancies beyond 20 weeks’ gestation (risk ratio [RR] 0·80, 95% CI 0·61–1·06; p=0·121). For participants with compliance of more than 80% from the last visit before pregnancy to 20 weeks’ gestation, the pre-eclampsia risk was 30 (21%) of 144 versus 47 (32%) of 149 (RR 0·66, CI 0·44–0·98; p=0·037). There were no serious adverse effects of calcium reported. Interpretation: Calcium supplementation that commenced before pregnancy until 20 weeks’ gestation, compared with placebo, did not show a significant reduction in recurrent pre-eclampsia. As the trial was powered to detect a large effect size, we cannot rule out a small to moderate effect of this intervention. ernal and Child Health.https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31818-X/fulltextPublisher's versio

Nutrient Intakes Linked to Better Health Outcomes Are Associated with Higher Diet Costs in the US

Degrees of nutrient intake and food groups have been linked to differential chronic disease risk. However, intakes of specific nutrients may also be associated with differential diet costs and unobserved differences in socioeconomic status (SES). The present study examined degrees of nutrient intake, for every key nutrient in the diet, in relation to diet cost and SES.Socio-demographic data for a stratified random sample of adult respondents in the Seattle Obesity Study were obtained through telephone survey. Dietary intakes were assessed using food frequency questionnaire (FFQ) (n = 1,266). Following standard procedures, nutrient intakes were energy-adjusted using the residual method and converted into quintiles. Diet cost for each respondent was estimated using Seattle supermarket retail prices for 384 FFQ component foods.Higher intakes of dietary fiber, vitamins A, C, D, E, and B12, beta carotene, folate, iron, calcium, potassium, and magnesium were associated with higher diet costs. The cost gradient was most pronounced for vitamin C, beta carotene, potassium, and magnesium. Higher intakes of saturated fats, trans fats and added sugars were associated with lower diet costs. Lower cost lower quality diets were more likely to be consumed by lower SES.Nutrients commonly associated with a lower risk of chronic disease were associated with higher diet costs. By contrast, nutrients associated with higher disease risk were associated with lower diet costs. The cost variable may help somewhat explain why lower income groups fail to comply with dietary guidelines and have highest rates of diet related chronic disease

Guidelines for the management of pregnancy in women with cystic fibrosis

Women with cystic fibrosis (CF) now regularly survive into their reproductive years in good health and wish to have a baby. Many pregnancies have been reported in the literature and it is clear that whilst the outcome for the baby is generally good and some mothers do very well, others find either their CF complicates the pregnancy or is adversely affected by the pregnancy. For some, pregnancy may only become possible after transplantation. Optimal treatment of all aspects of CF needs to be maintained from the preconceptual period until after the baby is born. Clinicians must be prepared to modify their treatment to accommodate the changing physiology during pregnancy and to be aware of changing prescribing before conception, during pregnancy, after birth and during breast feeding. This supplement offers consensus guidelines based on review of the literature and experience of paediatricians, adult and transplant physicians, and nurses, physiotherapists, dietitians, pharmacists and psychologists experienced in CF and anaesthetist and obstetricians with experience of CF pregnancy. It is hoped they will provide practical guidelines helpful to the multidisciplinary CF teams caring for pregnant women with CF