Global inequities in dietary calcium intake during pregnancy: a systematic review and meta-analysis.

BACKGROUND: Evidence shows that adequate calcium intake during pregnancy reduces the risk of hypertensive disorders of pregnancy. In most low- and middle-income countries (LMICs) the daily calcium intake is well below recommendations. Mapping calcium intake during pregnancy worldwide and identifying populations with low calcium intake will provide the evidence base for more targeted actions to improve calcium intake. OBJECTIVE: To assess dietary calcium intake during pregnancy worldwide. SEARCH STRATEGY: MEDLINE and EMBASE (from July 2004 to November 2017). SELECTION CRITERIA: Cross-sectional, cohort, and intervention studies reporting calcium intake during pregnancy. DATA COLLECTION AND ANALYSIS: Five reviewers working in pairs independently performed screening, extraction, and quality assessment. We reported summary measures of calcium intake and calculated the weighted arithmetic mean for high-income countries (HICs) and LMICs independently, and for geographic regions, among studies reporting country of recruitment, mean intake, and total number of participants. When available, inadequate intakes were reported. MAIN RESULTS: From 1880 citations 105 works met the inclusion criteria, providing data for 73 958 women in 37 countries. The mean calcium intake was 948.3 mg/day (95% CI 872.1-1024.4 mg/day) for HICs and 647.6 mg/day (95% CI 568.7-726.5 mg/day) for LMICs. Calcium intakes below 800 mg/day were reported in five (29%) countries from HICs and in 14 (82%) countries from LMICs. CONCLUSION: These results are consistent with a lack of improvement in calcium dietary intake during pregnancy and confirm the gap between HICs and LMICs, with alarmingly low intakes recorded for pregnant women in LMICs. From the public health perspective, in the absence of specific local data, calcium supplementation of pregnant women in these countries should be universal. TWEETABLE ABSTRACT: Despite dietary recommendations, women in LMICs face pregnancy with diets low in calcium.

The effect of calcium supplementation on blood pressure in non-pregnant women with previous pre-eclampsia: An exploratory, randomized placebo controlled study.

BACKGROUND: Epidemiological findings suggest that the link between poverty and pre-eclampsia might be dietary calcium deficiency. Calcium supplementation has been associated with a modest reduction in pre-eclampsia, and also in blood pressure (BP). METHODS: This exploratory sub-study of the WHO Calcium and Pre-eclampsia (CAP) trial aims to determine the effect of 500mg/day elemental calcium on the blood pressure of non-pregnant women with previous pre-eclampsia. Non-pregnant women with at least one subsequent follow-up trial visit at approximately 12 or 24weeks after randomization were included. RESULTS: Of 836 women randomized by 9 September 2014, 1st visit data were available in 367 women of whom 217 had previously had severe pre-eclampsia, 2nd visit data were available in 201 women. There was an overall trend to reduced BP in the calcium supplementation group (1-2.5mmHg) although differences were small and not statistically significant. In the subgroup with previous severe pre-eclampsia, the mean diastolic BP change in the calcium group (-2.6mmHg) was statistically larger than in the placebo group (+0.8mmHg), (mean difference -3.4, 95% CI -0.4 to -6.4; p=0.025). The effect of calcium on diastolic BP at 12weeks was greater than in those with non-severe pre-eclampsia (p=0.020, ANOVA analysis). CONCLUSIONS: There is an overall trend to reduced BP but only statistically significant in the diastolic BP of women with previous severe pre-eclampsia. This is consistent with our hypothesis that this group is more sensitive to calcium supplementation, however results need to be interpreted with caution.

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.

Same nutrient, different hypotheses: disparities in trials of calcium supplementation during pregnancy.

Calcium supplementation during pregnancy has been provided either to increase the intake in those with a deficiency or to obtain a pharmacologic, perhaps nonnutritional, effect in individuals with an adequate calcium intake. A systematic review, including only randomized, double-blind, controlled trials of calcium supplementation during pregnancy was prepared independently for the Cochrane Library and updated by us for this paper. In view of the heterogeneity of results included in the meta-analysis, a stratified analysis by baseline dietary calcium intake (mean calcium intake in the population < or >/=900 mg/d) was conducted. On the basis of the results of the 5 randomized, controlled trials available, the risk of high blood pressure was lower in women with low baseline dietary calcium [typical relative risk (TRR): 0.49; 95% CI: 0.38, 0.62]. Of the 4 trials in which subjects had adequate dietary calcium, the TRR of high blood pressure was 0.90 (95% CI: 0.81, 0.99). The risk of preeclampsia was considerably reduced in the 6 trials conducted in populations with low-calcium diets (TRR: 0.32; 95% CI: 0.21, 0.49) but was not reduced as much in women enrolled in the 4 trials with adequate-calcium diets (TRR: 0.86; 95% CI: 0.71, 1.05). On the basis of these results, it seems clear that calcium supplementation during pregnancy for women with deficient calcium intake is a promising preventive strategy for preeclampsia. Calcium supplementation in pregnancy should be evaluated definitively in an adequately sized trial conducted in a population with a low calcium intake because this is the most likely population to benefit from such a nutritional intervention. Long-term health benefits for the offspring are also an attractive possibility.

Long-term effect of calcium supplementation during pregnancy on the blood pressure of offspring: follow up of a randomised controlled trial.

OBJECTIVE: To explore the long-term effect of calcium supplementation during pregnancy on the offspring's blood pressure during childhood. DESIGN: Follow up of a population enrolled in a double blind, randomised, placebo controlled trial. SETTING: Perinatal research unit, World Health Organisation's collaborative research centre. SUBJECTS: 591 children at a mean age of 7 years whose mothers were randomly assigned during pregnancy to receive 2 g/day of elemental calcium (n = 298) or placebo (n = 293). MAIN OUTCOME MEASURES: Mean blood pressure and rate of high blood pressure of children. RESULTS: Overall, systolic blood pressure was lower in the calcium group (mean difference -1.4 mm Hg; 95% confidence interval -3.2 to 0.5) than in the placebo group. The effect was found predominantly among children whose body mass index at assessment was above the median for this population (mean difference in systolic blood pressure -5.8 mm Hg (-9.8 mm Hg to -1.7 mm Hg) for children with an index > 17.5 and -3.2 mm Hg (-6.3 mm Hg to -0.1 mm Hg) for those with an index of > 15.7 to 17.5). The risk of high systolic blood pressure was also lower in the calcium group than in the placebo group (relative risk 0.59; 0.39 to 0.90) and particularly among children in the highest fourth of body mass index (0.43; 0.26 to 0.71). CONCLUSION: Calcium supplementation during pregnancy is associated with lower systolic blood pressure in the offspring, particularly among overweight children.

Calcium supplementation to prevent hypertensive disorders of pregnancy.

BACKGROUND: Calcium supplementation has been reported to reduce blood pressure in pregnant and nonpregnant women. We undertook this prospective study to determine the effect of calcium supplementation on the incidence of hypertensive disorders of pregnancy (gestational hypertension and preeclampsia) and to determine the value of urinary calcium levels as a predictor of the response. METHODS: We studied 1194 nulliparous women who were in the 20th week of gestation at the beginning of the study. The women were randomly assigned to receive 2 g per day of elemental calcium in the form of calcium carbonate (593 women) or placebo (601 women). Urinary excretion of calcium and creatinine was measured before calcium supplementation was begun. The women were followed to the end of their pregnancies, and the incidence of hypertensive disorders of pregnancy was determined. RESULTS: The rates of hypertensive disorders of pregnancy were lower in the calcium group than in the placebo group (9.8 percent vs. 14.8 percent; odds ratio, 0.63; 95 percent confidence interval, 0.44 to 0.90). The risk of these disorders was lower at all times during gestation, particularly after the 28th week of gestation (P = 0.01 by life-table analysis), in the calcium group than in the placebo group, and the risk of both gestational hypertension and preeclampsia was also lower in the calcium group. Among the women who had low ratios of urinary calcium to urinary creatinine (less than or equal to 0.62 mmol per millimole) during the 20th week of gestation, those in the calcium group had a lower risk of hypertensive disorders of pregnancy (odds ratio, 0.56; 95 percent confidence interval, 0.29 to 1.09) and less of an increase in diastolic and systolic blood pressure than the placebo group. The pattern of response was similar among the women who had a high ratio of urinary calcium to urinary creatinine during the 20th week of gestation, but the differences were smaller. CONCLUSIONS: Pregnant women who receive calcium supplementation after the 20th week of pregnancy have a reduced risk of hypertensive disorders of pregnancy.

Biochemical changes associated with blood pressure reduction induced by calcium supplementation during pregnancy.

In a study population that comprised 34 normal black pregnant women, biochemical changes are compared between a group of women who received 1.5 gm of calcium supplementation a day and a group of women who received placebos. The blood pressure-lowering effect of calcium supplementation appears to involve a mechanism that relates parathyroid hormone and plasma renin activity. Other alterations in calcium and magnesium metabolism, as reflected by increased urinary calcium excretion and serum magnesium levels, may also contribute to this effect. Subgroups of study participants with initial (less than 26 weeks' gestation) low levels of serum calcium and plasma renin activity are the ones with the largest reductions in blood pressure. Whether these alterations can produce a reduction in the incidence of pregnancy-induced hypertension is the next question to be answered in this area.

The relationship between calcium intake and pregnancy-induced hypertension: up-to-date evidence.

In 1980 we pointed to a relationship between calcium intake and pregnancy-induced hypertension. The original epidemiologic observations showed an inverse association between calcium intake and incidence of eclampsia after adjusting by several confounding factors. A series of recent randomized clinical trials have demonstrated a reduction in blood pressure with calcium supplementation in animals, in healthy and mildly hypertensive subjects, and in pregnant women. It is hypothesized that parathyroid hormone plays a role since it is affected by calcium intake and can partially regulate the concentration of free cytosolic ionized calcium, thus triggering smooth muscle contraction. Randomized clinical trials showing a reduction in the incidence of pregnancy-induced hypertension with calcium supplementation have not as yet been published. However, preliminary observations appear to support this hypothesis.

Calcium supplementation reduces blood pressure during pregnancy: results of a randomized controlled clinical trial.

Fifty-two healthy pregnant women were enrolled in a double-blind, randomized, controlled clinical trial. After the 26th week of gestation, the women were given either 1.5 g of elemental calcium per day or a placebo. Subjects in the calcium group, after adjustment for race and initial blood pressure (BP), had a term mean systolic and diastolic BP value of 4-5 mmHg lower than those in the placebo group (P less than .05). The incidence of pregnancy-induced hypertension was 11.1% in the placebo group and 4.0% in the calcium group, a nonsignificant difference. Combining these values with previous data, we found a dose-effect relationship between calcium intake and BP reduction during the third trimester of pregnancy. Further research should be directed at understanding the mechanism of this effect and trying to demonstrate a reduction in pregnancy-induced hypertension with calcium supplementation in a larger population.

Preliminary evidence of the effect of calcium supplementation on blood pressure in normal pregnant women.

In this study the hypothesis that calcium supplementation during pregnancy can modify blood pressure patterns in a population of normal pregnant women was tested. Thirty-six women with normal single pregnancies, between 20 and 35 years of age, in the second trimester of gestation (15 weeks), were randomly assigned to receive 1 gm of calcium per day (n = 11), 2 gm per day (n = 11), or a placebo (n = 14). No differences were observed at the times of admission into the study (baseline) in demographic and clinical variables or in the calcium intake of each group. Baseline blood pressure measures in several positions also were not different. After the initial blood pressure measures (fifteenth week), five follow-up blood pressure measures were obtained. The supplemented groups had significantly lower diastolic blood pressure than the control subjects between the twentieth and twenty-fourth weeks of gestation. Thereafter, an increase in the control group and the group receiving 1 gm of calcium was observed, but levels were similar at term. On the contrary, patients receiving 2 gm of calcium had blood pressure values that remained significantly lower throughout the third trimester. No differences or clear patterns were observed in the blood levels of calcium, magnesium, phosphorus, and proteins between and within groups during gestation. A possible explanation involving parathyroid hormone is attempted.

Reduction of blood pressure with calcium supplementation in young adults.

Epidemiologic and animal studies have suggested an inverse relationship between calcium intake and BP. Furthermore, calcium intake seems to be inversely correlated with the incidence of eclampsia in pregnancy. In a randomized clinical trial, young adults were allocated to a calcium-supplemented group receiving 1 g/day of elemental calcium (15 men and 15 women) or a placebo group (14 women and 13 men) for a period of 22 weeks. The calcium-supplemented group showed a significant decrease in diastolic BP; this effect was stabilized after nine weeks in women and six weeks in men. The reduction in diastolic BP was 5.6% and 9% from the initial values for women and men, respectively. This study supports epidemiologic and animal evidence of the effect of calcium intake on BP and suggests the need for more research exploring the mechanisms involved in the observed effect.