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

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. Longterm health benefits for the offspring are also an attractive possibility.Am J Clin Nutr 2000;71(suppl):1375S-9S.

World Health Organisation multicentre randomised trial of supplementation with vitamins C and E among pregnant women at high risk for pre‐eclampsia in populations of low nutritional status from developing countries

“…Only in the event of a sig-nificant overall effect of vitamin E and C supplementation on the primary outcomes, and according to the protocol, did we plan to investigate the effect of compliance levels on the treatment effect, that is, a 'Dose Effect' relationship. All analyses were performed using stata 8 15 were followed in all centres and monitored by the coordinating unit on a regular basis.…”

“…5,6 Nutritional supplementation during pregnancy may theoretically prevent complications by two mechanisms. 8 The supplemented nutrient can have a pharmacological effect in well-nourished women, a concept explored in recent trials 4,6,9 or may achieve benefit through correction of a deficiency secondary to low dietary intake. 10 The present trial evaluates the latter concept: whether or not supplementation with vitamins C and E prevents pre-eclampsia and low birthweight (LBW) among women at high risk for pre-eclampsia from communities at risk of poor nutritional status in developing countries.…”

Summary of the NHLBI Working Group on Research on Hypertension During Pregnancy

“…46 Indeed, although this review has stressed a current and very plausible hypothesis, it would be remiss not to summarize other postulates under consideration. These include abnormalities in the mother's circulatory adaptations to pregnancy, 47,48 maternal endothelial dysfunction secondary to cytokines, 49 altered autocoid systems, 50 vitamin and mineral deficiencies, 51 infectious agents similar to those linked to atherosclerosis, 52 impairment of the normal barriers against the importation of fetal and trophoblastic material into the maternal circulation, 53 and a combination of these factors with those described in detail above. This emphasizes the value and need for clinical trials that incorporate mechanistic studies to increase understanding further.…”

Case report: Successful pregnancy following maternal small bowel reconstruction for congenital short bowel syndrome

“…Selenium and copper deficiencies may both be associated with adverse pregnancy outcome, including reduced fetal growth, 17 while calcium deficiency may be associated with abnormal fetal development, pregnancy-induced hypertension and preterm delivery. 18 The lack of ileal binding sites meant the need for vitamin B 12 supplementation, the lack of which has been associated with neural tube defects, 19 intrauterine death and possible adverse neurobehavioural development. 20 An inadequate intake of folic acid during the peri-conceptual period has also been associated with neural tube defect; a 5-mg daily supplement is recommended in women with malabsorption states and was Case report given in this case.…”