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

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Abstract
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.