A simulation study to improve calcium intake through wheat flour fortification.

OBJECTIVE: To simulate the impact on calcium intake - effectiveness and safety - of fortifying wheat flour with 200, 400 and 500 mg of calcium per 100 g of flour. DESIGN: Secondary analysis of cross-sectional data collected through repeated 24 h dietary recalls using the Iowa State University Intake Modelling, Assessment and Planning Program. SETTING: Urban cities in the National Health and Nutrition Survey of Argentina (ENNyS 2018-2019). PARTICIPANTS: 21 358 participants, including children, adolescents and adults. RESULTS: Most individuals in all age groups reported consuming wheat flour. The prevalence of low calcium intake was above 80 % in individuals older than 9 years. Simulating the fortification of 500 mg of calcium per 100 g of wheat flour showed that the prevalence of low calcium intake could be reduced by more than 40 percentage points in girls and women aged 19 to less than 51 years and boys and men aged 4 to less than 71 years, while it remained above 65 % in older ages. The percentages above the upper intake level remained below 1·5 % in all age groups. CONCLUSIONS: Calcium flour fortification could be further explored to improve calcium intake. Subnational simulations could be performed to identify groups that might not be reached by this strategy that could be explored in Argentina. This analysis could be used to advocate for a strategy to fortify wheat flour.

Calcium supplementation for people with overweight or obesity.

BACKGROUND: Obesity is a major health problem worldwide as it can lead to high blood pressure, heart disease, stroke, diabetes, and insulin resistance. The prevalence of overweight and obesity is increasing worldwide across different age groups. There is evidence of an inverse relationship between calcium intake and body weight. The clinical relevance of a small reduction in body weight has been questioned. However, at a population level, a small effect could mitigate the observed global trends. OBJECTIVES: To assess the effects of calcium supplementation on weight loss in individuals living with overweight or obesity. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS (Latin American and Caribbean Health Science Information database), and two clinical trials registries. The date of the last search of all databases (except Embase) was 10 May 2023. No language restrictions were applied. SELECTION CRITERIA: We included randomised controlled trials evaluating the effect of calcium in participants with overweight or obesity of any age or gender. We excluded studies in participants with absorption problems. We included studies of any dose with a minimum duration of two months. We included the following comparisons: calcium supplementation versus placebo, calcium-fortified food or beverage versus placebo, or calcium-fortified food or beverage versus non-calcium-fortified food or beverage. We excluded studies that evaluated the effect of calcium and vitamin D or mixed minerals compared to placebo. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcomes were body weight, health-related quality of life, and adverse events. Our secondary outcomes were anthropometric measures other than body weight, all-cause mortality, and morbidity. MAIN RESULTS: We found 18 studies that evaluated the effect of calcium compared to placebo or control, with a total of 1873 randomised participants (950 participants in the calcium supplementation groups and 923 in the control groups). All included studies gave oral calcium supplementation as the intervention. We did not find any studies evaluating calcium-fortified foods. We excluded 38 studies, identified four ongoing studies, and listed one study as 'awaiting classification'. Sixteen studies compared calcium supplementation to placebo; two studies compared different doses of calcium supplementation. Doses ranged from very low (0.162 g of calcium/day) to high (1.5 g of calcium/day). Most studies were performed in the USA and Iran, lasted less than six months, and included only women. Low-certainty evidence suggests that calcium supplementation compared to placebo or control may result in little to no difference in body weight (mean difference (MD) -0.15 kg, 95% confidence interval (CI) -0.55 to 0.24; P = 0.45, I2 = 46%; 17 studies, 1317 participants; low-certainty evidence). We downgraded the certainty of the evidence by two levels for risk of bias and heterogeneity. None of the included studies reported health-related quality of life, all-cause mortality, or morbidity/complications as outcomes. Only five studies assessed or reported adverse events. Low-certainty evidence suggests a low frequency of adverse events, with no clear difference between intervention and control groups. Moderate-certainty evidence shows that calcium supplementation compared to placebo or control probably results in a small reduction in body mass index (BMI) (MD -0.18 kg/m2,95% CI -0.22 to -0.13; P < 0.001, I2 = 0%; 9 studies, 731 participants) and waist circumference (MD -0.51 cm, 95% CI -0.72 to -0.29; P < 0.001, I2 = 0%; 6 studies, 273 participants). Low-certainty evidence suggests that calcium supplementation compared to placebo or control may result in a small reduction in body fat mass (MD -0.34 kg, 95% CI -0.73 to 0.05; P < 0.001, I2 = 97%; 12 studies, 812 participants). AUTHORS' CONCLUSIONS: Calcium supplementation for eight weeks to 24 months may result in little to no difference in body weight in people with overweight or obesity. The current evidence is of low certainty, due to concerns regarding risk of bias and statistical heterogeneity. We found that the degree of heterogeneity might be partly explained by calcium dosage, the presence or absence of a co-intervention, and whether an intention-to-treat analysis was pursued. While our analyses suggest that calcium supplementation may result in a small reduction in BMI, waist circumference, and fat mass, this evidence is of low to moderate certainty. Future studies could investigate the effect of calcium supplementation on lean body mass to explore if there is a change in body composition.

Including calcium-fortified water or flour in modeled diets based on local foods could improve calcium intake for women, adolescent girls, and young children in Bangladesh, Uganda, and Guatemala.

Adequate calcium intake is essential for health, especially for infants, children, adolescents, and women, yet is difficult to achieve with local foods in many low- and middle-income countries. Previous analysis found it was not always possible to identify food-based recommendations (FBRs) that reached the calcium population recommended intake (PRI) for these groups in Bangladesh, Guatemala, and Uganda. We have modeled the potential contribution of calcium-fortified drinking water or wheat flour to FBR sets, to fill the remaining intake gaps. Optimized diets containing fortified products, with calcium-rich local foods, achieved the calcium PRI for all target groups. Combining fortified water or flour with FBRs met dietary intake targets for adolescent girls in all geographies and allowed a reduction from 3-4 to the more feasible 1-2 FBRs. Water with a calcium concentration of 100 mg/L with FBRs was sufficient to meet calcium targets in Uganda, but higher concentrations (400-500 mg/L) were mostly required in Guatemala and Bangladesh. Combining calcium-fortified wheat flour at 400 mg/100 g of flour and the FBR for small fish resulted in diets meeting the calcium PRI in Bangladesh. Calcium-fortified water or flour could improve calcium intake for vulnerable populations, especially when combined with FBRs based on locally available foods.

Could local foods achieve recommended calcium intakes for nutritionally vulnerable populations in Uganda, Guatemala, and Bangladesh?

Globally, dietary intake of calcium is often insufficient, and it is unclear if adequacy could be achieved by promoting calcium-rich local foods. This study used linear programming and household consumption data from Uganda, Bangladesh, and Guatemala to assess whether local foods could meet calcium population reference intakes (Ca PRIs). The most promising food-based approaches to promote dietary calcium adequacy were identified for 12- to 23-month-old breastfed children, 4- to 6-year-old children, 10- to 14-year-old girls, and nonpregnant and nonbreastfeeding (NPNB) women of reproductive age living in two regions of each country. Calcium-optimized diets achieved 75-253% of the Ca PRI, depending on the population, and were <100% for 4- to 6-year-olds in one region of each country and 10- to 14-year-old girls in Sylhet, Bangladesh. The best food sources of calcium were green leafy vegetables and milk, across geographic locations, and species of small fish, nixtamalized (lime-treated) maize products, sesame seeds, and bean varieties, where consumed. Food-based recommendations (FBRs) achieving the minimum calcium threshold were identified for 12- to 23-month-olds and NPNB women across geographic locations, and for 4- to 6-year-olds and 10-to 14-year-old girls in Uganda. However, for 4- to 6-year-olds and 10- to 14-year-old girls in Bangladesh and Guatemala, calcium-adequate FBRs could not be identified, indicating a need for alternative calcium sources or increased access to and consumption of local calcium-rich foods.

Global inequities in cesarean section deliveries and required resources persist.

OBJECTIVE: The purpose of this study was to estimate the global distribution and financial cost associated with the inequities present in the use of cesarean sections (CS) worldwide. STUDY DESIGN: We used the latest estimates on CS rates published by WHO and we adopted 10-15 % as the range of CS rates that are considered optimal for adequate use. We calculated the cost (in USD) to achieve CS rates of 10-15 % for countries that reported rates below 10 %. We also calculated the cost of CS rates in excess (>15 % and > 20 %) by estimating how much it would cost to reduce the rates to 10-15 % for each of those countries. RESULTS: 137 countries are included in this analysis with updated data on CS rates between the years 2010 and 2018. Our analysis found that 36 countries reported CS rates < 10 %, whereas 91 countries reported CS rates > 15 % (a majority of which were > 20 %); only 10 countries reported CS rates between 10 and 15 %. The cost of CS exceeding a rate of 15 % is estimated to be $9,586,952,466 including inflation and exceeding 20 % is $7.169.248.033 (USD). The cost of achieving "needed" CS among countries with CS rates < 10 % is $612,609,418 (USD). The cost of cesarean sections exceeding 15 % has increased by 313 % between 2008 and more recent years, accruing $7 billion (USD) more in surplus since 2008. The reallocation of CS funding would save the global economy $9 billion (USD). CONCLUSION: Global inequities in CS performed and associated costs have increased since 2008, resulting in a disproportionate number of resources allocated.

Calcium concentration of drinking water to improve calcium intake: A simulation study.

The risk of inadequate calcium intake is a worldwide problem. We performed a simulation exercise on the impact, effectiveness, and safety of increasing calcium levels in drinking water using the 2019 Health and Nutrition National Survey of Argentina, which provides water intake and water sources data at the individual level. We simulated the distribution of calcium intake assuming a calcium concentration of 100 mg of calcium per liter of tap water and 400 mg of calcium per liter of bottled water. After the simulation, all population groups had a slightly improved calcium intake. Higher impacts were observed in adults, as reported water intake was higher in adults 19-51 years old. In young adult women, the estimated calcium intake inadequacy decreased from 91.0% to 79.7% when calcium was increased in tap water and to 72.2% when calcium was increased in tap and bottled water. The impact was lower in adolescents and older adults who have higher calcium recommendations and reported lower water intake. Increased calcium concentration of water could improve calcium intake in Argentina, especially in adults as their reported water intake is higher. Combining more than one strategy to improve calcium intake might be required for countries like Argentina with low calcium intake.

Calculation of the contribution of water to calcium intake in low- and middle-income countries.

Dietary calcium intake is low in many countries, particularly in low- and middle-income countries (LMICs). Water is often overlooked as a source of dietary calcium despite it being universally consumed and providing good calcium bioavailability. Our objective was to assess water distribution systems in LMICs and to develop a formula to simulate the contribution of different water sources to calcium availability. We calculated the contribution of drinking water considering different calcium concentration levels to estimate total calcium availability. We consider a country's households' access to drinking water sources and the distribution of the country's population by age and gender. Calcium availability could be increased by an average of 49 mg of calcium per person per day in the 62 countries assessed if calcium in drinking water was considered. In 22 (31%) of the countries studied, 80% of households are supplied by water sources that could increase calcium availability. Improving calcium concentration in water could be considered as a strategy in LMICs to slightly improve calcium availability.

Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial.

PURPOSE: Preclinical data suggest that antiprogestins inhibit the growth of luminal breast carcinomas that express higher levels of progesterone receptor isoform A (PRA) than isoform B (PRB). Thus, we designed a presurgical window of opportunity trial to determine the therapeutic effects of mifepristone in patients with breast cancer, based on their high PRA/PRB isoform ratio (MIPRA; NCT02651844). PATIENTS AND METHODS: Twenty patients with luminal breast carcinomas with PRA/PRB > 1.5 (determined by Western blots), and PR ≥ 50%, naïve from previous treatment, were included for mifepristone treatment (200 mg/day orally; 14 days). Core needle biopsies and surgical samples were formalin fixed for IHC studies, while others were snap-frozen to perform RNA sequencing (RNA-seq), proteomics, and/or Western blot studies. Plasma mifepristone levels were determined using mass spectrometry. The primary endpoint was the comparison of Ki67 expression pretreatment and posttreatment. RESULTS: A 49.62% decrease in Ki67 staining was observed in all surgical specimens compared with baseline (P = 0.0003). Using the prespecified response parameter (30% relative reduction), we identified 14 of 20 responders. Mifepristone induced an increase in tumor-infiltrating lymphocytes; a decrease in hormone receptor and pSer118ER expression; and an increase in calregulin, p21, p15, and activated caspase 3 expression. RNA-seq and proteomic studies identified downregulated pathways related to cell proliferation and upregulated pathways related to immune bioprocesses and extracellular matrix remodeling. CONCLUSIONS: Our results support the use of mifepristone in patients with luminal breast cancer with high PRA/PRB ratios. The combined effects of mifepristone and estrogen receptor modulators warrant clinical evaluation to improve endocrine treatment responsiveness in these patients. See related commentary by Ronchi and Brisken, p. 833.

Tendencia de cesáreas en entidades privadas de la provincia de Buenos Aires, Argentina (2017-2021) / Cesarean section trends in private entities in the province of Buenos Aires, Argentina (2017-2021)

Resumen OBJETIVO: Evaluar las tasas de cesárea en la finalización de embarazos registrados en el sector privado de la Obra Social de la provincia de Buenos Aires (Instituto de Obra Médico Asistencial) entre los años 2017 a 2021. MATERIALES Y MÉTODOS: Estudio analítico y descriptivo de cesáreas registradas en el Sistema de Modulación Centro Único de Auditoría y Fiscalización IOMA (CUAFI) de las 13 regiones sanitarias de la provincia de Buenos Aires. Se describen los porcentajes de cesárea por año y por región sanitaria. RESULTADOS: Se registraron 75,244 partos únicos. En el año 2017 el porcentaje de cesáreas se incrementó de 69.0% (12,600 cesáreas de 18,258 partos) a 73.6% (8,232 cesáreas de 11,180 partos) en 2021. Los mayores porcentajes de cesárea se registraron en la Región IV (83.6%), la Región XIV (81.7%) y Región X (78.9%). CONCLUSIÓN: El alto porcentaje de cesáreas registrado y el incremento en los últimos años muestra la necesidad de diseñar intervenciones para reducir su tasa. Será importante contar con información de sus indicaciones y explorar intervenciones destinadas al personal de salud y a las mujeres para reducir su práctica.

Abstract OBJECTIVE: To evaluate the rates of caesarean section in the termination of pregnancies registered in the private sector of the Obra Social of the province of Buenos Aires (Instituto de Obra Médico Asistencial) between 2017 and 2021. MATERIALS AND METHODS: Analytical and descriptive study of caesarean sections registered in the Modulation System of the IOMA Single Audit and Control Centre (CUAFI) of the 13 health regions of the province of Buenos Aires. The percentages of caesarean sections per year and per health region are described. RESULTS: 75,244 singleton deliveries were registered in the private sector of the Instituto de Obra Médico Asistencial. In 2017, the percentage of caesarean sections increased from 69.0% (12,600 caesarean sections out of 18,258 deliveries) to 73.6% (8,232 caesarean sections out of 11,180 deliveries) in 2021. The highest caesarean section rates were recorded in Region IV (83.6%), Region XIV (81.7%) and Region X (78.9%). CONCLUSION: The high percentage of caesarean sections recorded and the increase in recent years shows the need to design interventions to decrease the rate. It is important to have information on the indications for caesarean section and to explore interventions aimed at health personnel and women to reduce the rate.

Calcium for pre-eclampsia prevention: A systematic review and network meta-analysis to guide personalised antenatal care.

BACKGROUND: Calcium supplementation reduces the risk of pre-eclampsia, but questions remain about the dosage to prescribe and who would benefit most. OBJECTIVES: To evaluate the effectiveness of high (≥1 g/day) and low (<1 g/day) calcium dosing for pre-eclampsia prevention, according to baseline dietary calcium, pre-eclampsia risk and co-interventions, and intervention timing. SEARCH STRATEGY: CENTRAL, PubMed, Global Index Medicus and CINAHL, from inception to 2 February 2021, clinical trial registries, reference lists and expert input (CRD42018111239). SELECTION CRITERIA: Randomised controlled trials of calcium supplementation for pre-eclampsia prevention, for women before or during pregnancy. Network meta-analysis (NMA) also included trials of different calcium doses. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted published data. The meta-analysis employed random-effects models and the NMA, a Bayesian random-effects model, to obtain direct and indirect effect estimates. MAIN RESULTS: The meta-analysis included 30 trials (N = 20 445 women), and the NMA to evaluate calcium dosage included 25 trials (N = 15 038). Calcium supplementation prevented pre-eclampsia similarly with a high dose (RR 0.49, 95% CI 0.36-0.66) or a low dose (RR 0.49, 95% CI 0.36-0.65). By NMA, high-dose (vs low-dose) calcium did not differ in effect (RR 0.79, 95% CI 0.43-1.40). Calcium was similarly effective regardless of baseline pre-eclampsia risk, vitamin D co-administration or timing of calcium initiation, but calcium was ineffective among women with adequate average baseline calcium intake. CONCLUSIONS: Low- and high-dose calcium supplementation are effective for pre-eclampsia prevention in women with low calcium intake. This has implications for population-level implementation where dietary calcium is low, and targeted implementation where average intake is adequate. TWEETABLE ABSTRACT: A network meta-analysis of 25 trials found that low-dose calcium supplementation (<1 g/day) is as effective as high-dose calcium supplementation (≥1 g/day) in halving the risk of pre-eclampsia when baseline calcium intake is low.

Fortification of staple foods with calcium: a novel costing tool to inform decision making.

Low calcium intake and its impact on maternal and child health are a major concern in low- and middle-income countries. Given the low calcium in diet, as well as the low adherence and acceptability of calcium pills in those settings, the discussion about policies to increase calcium intake has moved toward staple food fortification strategies. Nevertheless, there is scarce information on the economic feasibility of implementing these strategies. We aimed to design and propose a novel costing tool to estimate the cost of the flour fortification with calcium by carrying out a literature review about costing studies for staple food fortification programs and costing tools previously developed. A deliberative meeting with stakeholders was held to discuss and face-validate the conceptual framework proposed. We showed the costing tool application for the case of Costa Rica (a country with a population with low calcium intake), including the absolute cost of the staple food fortification production process, the incremental cost of fortification according to the public/private sector, and the incremental cost by target population. This open-source and publicly available costing tool can be useful to inform policymaking in countries considering the implementation of staple food fortification programs.

Characteristics and birth outcomes of pregnant adolescents compared to older women: An analysis of individual level data from 140,000 mothers from 20 RCTs.

BACKGROUND: Adolescence is a critical period of maturation when nutrient needs are high, especially among adolescents entering pregnancy. Using individual-level data from 140,000 participants, we examined socioeconomic, nutrition, and pregnancy and birth outcomes for adolescent mothers (10-19 years) compared to older mothers in low and middle-income countries. METHODS: This study was conducted between March 16, 2018 and May 25, 2021. Data were obtained from 20 randomised controlled trials of micronutrient supplementation in pregnancy. Stratified analyses were conducted by age (10-14 years, 15-17 years, 18-19 years, 20-29 years, 30-39 years, 40+ years) and geographical region (Africa, Asia). Crude and confounder-adjusted means, prevalence and relative risks of pregnancy, nutrition and birth outcomes were estimated using multivariable linear and log-binomial regression models with 95% confidence intervals. FINDINGS: Adolescent mothers comprised 31.6% of our data. Preterm birth, small-for-gestational age (SGA), low birthweight (LBW) and newborn mortality followed a U-shaped trend in which prevalence was highest among the youngest mothers (10-14 years) and then reduced gradually, but increased again for older mothers (40+ years). When compared to mothers aged 20-29 years, there was a 23% increased risk of preterm birth, a 60% increased risk of perinatal mortality, a 63% increased risk of neonatal mortality, a 28% increased risk of LBW, and a 22% increased risk of SGA among mothers 10-14 years. Mothers 40+ years experienced a 22% increased risk of preterm birth and a 103% increased risk of stillbirth when compared to the 20-29 year group. INTERPRETATION: The youngest and oldest mothers suffer most from adverse pregnancy and birth outcomes. Policy and programming agendas should consider both biological and socioeconomic/environmental factors when targeting these populations. FUNDING: Bill and Melinda Gates Foundation (Grant No: OP1137750).

Calcium deficiency worldwide: prevalence of inadequate intakes and associated health outcomes.

Dietary calcium deficiency is considered to be widespread globally, with published estimates suggesting that approximately half of the world's population has inadequate access to dietary calcium. Calcium is essential for bone health, but inadequate intakes have also been linked to other health outcomes, including pregnancy complications, cancers, and cardiovascular disease. Populations in low- and middle-income countries (LMICs) are at greatest risk of low calcium intakes, although many individuals in high-income countries (HICs) also do not meet recommendations. Paradoxically, many LMICs with lower calcium intakes show lower rates of osteoporotic fracture as compared with HICs, though data are sparse. Calcium intake recommendations vary across agencies and may need to be customized based on other dietary factors, health-related behaviors, or the risk of calcium-related health outcomes. The lack of standard methods to assess the calcium status of an individual or population has challenged efforts to estimate the prevalence of calcium deficiency and the global burden of related adverse health consequences. This paper aims to consolidate available evidence related to the global prevalence of inadequate calcium intakes and associated health outcomes, with the goal of providing a foundation for developing policies and population-level interventions to safely improve calcium intake and status where necessary.

Interventions to improve calcium intake through foods in populations with low intake.

Calcium intake remains inadequate in many low- and middle-income countries, especially in Africa and South Asia, where average intakes can be below 400 mg/day. Given the vital role of calcium in bone health, metabolism, and cell signaling, countries with low calcium intake may want to consider food-based approaches to improve calcium consumption and bioavailability within their population. This is especially true for those with low calcium intake who would benefit the most, including pregnant women (by reducing the risk of preeclampsia) and children (by reducing calcium-deficiency rickets). Specifically, some animal-source foods that are naturally high in bioavailable calcium and plant foods that can contribute to calcium intake could be promoted either through policies or educational materials. Some food processing techniques can improve the calcium content in food or increase calcium bioavailability. Staple-food fortification with calcium can also be a cost-effective method to increase intake with minimal behavior change required. Lastly, biofortification is currently being investigated to improve calcium content, either through genetic screening and breeding of high-calcium varieties or through the application of calcium-rich fertilizers. These mechanisms can be used alone or in combination based on the local context to improve calcium intake within a population.

The peripartum period involvement in the development of post-partum depression. A prospective cohort study.

PURPOSE: This study explores postpartum depression (PPD) in women who screened negative in mid-pregnancy to assess the impact of the peripartum period on the development of depressive symptoms. METHODS: A prospective cohort study was carried out in two facilities in Argentina. The Edinburgh postnatal depression scale (EPDS) scale was applied to pregnant women between weeks 20-24 gestation, and those screening negative (<10) were included in the cohort. Participants were followed up until the 4th week postpartum, when the EPDS was repeated. If positive, a semi-structured clinical interview was applied (MINI) to define the diagnosis. RESULTS: A total of 112 pregnant women were eligible for the follow-up. At the 4th week postpartum, 14 women (12.5%, CI 95% 7.0; 20.1) screened positive using a cutoff point of 10 or more in the EPDS. Of those screened positive in the EPDS, two participants (1.8%, CI 95% 0.2-6.3) had a Major Depressive Disorder. Newborn admission to the Intensive Care Unit, hospitalization of the newborn after discharge, abuse during childbirth, and lack of company during labor were identified as peripartum risk factors. CONCLUSIONS: This study reinforces the relevance of women and newborn mental health care during the hospitalization process surrounding peripartum. The women and newborn hospitalization process should be better explored to understand the contribution to PPD and design and test strategies to alleviate the impact of maternal depression.

Calcium supplementation for the prevention of hypertensive disorders of pregnancy: current evidence and programmatic considerations.

Most low- and middle-income countries present suboptimal intakes of calcium during pregnancy and high rates of mortality due to maternal hypertensive disorders. Calcium supplementation during pregnancy is known to reduce the risk of these disorders and associated complications, including preeclampsia, maternal morbidity, and preterm birth, and is, therefore, a recommended intervention for pregnant women in populations with low dietary calcium intake (e.g., where ≥25% of individuals in the population have intakes less than 800 mg calcium/day). However, this intervention is not widely implemented in part due to cost and logistical issues related to the large dose and burdensome dosing schedule (three to four 500-mg doses/day). WHO recommends 1.5-2 g/day but limited evidence suggests that less than 1 g/day may be sufficient and ongoing trials with low-dose calcium supplementation (500 mg/day) may point a path toward simplifying supplementation regimens. Calcium carbonate is likely to be the most cost-effective choice, and it is not necessary to counsel women to take calcium supplements separately from iron-containing supplements. In populations at highest risk for preeclampsia, a combination of calcium supplementation and food-based approaches, such as food fortification with calcium, may be required to improve calcium intakes before pregnancy and in early gestation.