Trial of Calcium to Prevent Preeclampsia

Levine, Richard J.; Hauth, John C.; Curet, Luis B.; Sibai, Baha M.; Catalano, Patrick M.; Morris, Cynthia D.; DerSimonian, Rebecca; Esterlitz, Joy; Raymond, Elizabeth G.; Bild, Diane E.; Clemens, John D.; Cutler, Jeffrey A.; Ewell, Marian; Friedman, Steven A.; Goldenberg, Robert L.; Jacobson, Sig Linda; Joffe, Gary M.; Klebanoff, Mark A.; Petrulis, Alice Stollenwerk

doi:10.1056/nejm199707103370201

Cited by 551 publications

(202 citation statements)

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“…In this regard, Purwar et al have reported that preeclampsia in a calcium group was 2% and in placebo group was 12% and this difference was significant 15 . But Levine et al have found no difference between calcium and placebo group in preeclampsia 16 . Belizán et al have demonstrated that the incidence of preeclampsia in the placebo group was 4% and in calcium group was 3%, which did not differ significantly 8 .…”

Section: Discussionmentioning

confidence: 99%

Calcium supplementation in pregnancy and prevention of hypertensive disorders in elderly women

Aghamohammadi¹,

Zafari²

2015

ScienceAsia

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Preeclampsia is a major cause of maternal and neonatal death and morbidity. Elderly women are at high risk for this complication. This study assesses the effect of calcium supplementation during pregnancy on preeclampsia in women aged over 35. Singleton healthy pregnant women over 35 with a normal blood pressure were randomly assigned to receive 1000 mg/day of elemental calcium or placebo between the 18th and 20th weeks. From 89 women recruited in this study, 5 women in the calcium group and 4 women in the placebo group were excluded during the treatment as it was not possible to follow up their status. Finally, 80 women completed this study and were followed up until delivery. The incidence of preeclampsia was assessed in these 80 women (40 women in placebo and 40 women in the calcium group). The incidence of preeclampsia was significantly lower in the calcium group (15%) than in the placebo group (35%) (p = 0.035). Calcium supplementation appears to reduce the occurrence of preeclampsia and its related preterm birth in women singletons.

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Section: Discussionmentioning

confidence: 99%

Calcium supplementation in pregnancy and prevention of hypertensive disorders in elderly women

Aghamohammadi¹,

Zafari²

2015

ScienceAsia

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“…Women took 86% of the supplement on average, increased their urinary excretion of calcium, and had a reduced risk of pregnancy-induced hypertension and preeclampsia although, in the case of the latter, the 95% CI of the odds ratios included unity. In contrast, the trial conducted by the NIH studied the effect of calcium supplementation (2000 mg/d) Same nutrient, different hypotheses: disparities in trials of calcium supplementation during pregnancy [1][2][3] in 4336 women without a calcium deficiency (mean baseline intake: 1130 mg/d) to achieve a pharmacologic, preventive effect rather than to correct a nutritional deficit (1). Women took an average of 64% of the supplement and only 20% of them used > 90% of the medication (1).…”

Section: Disparities Between the 2 Largest Trialsmentioning

confidence: 99%

“…These RRs are not statistically significant, probably because of a smaller number of events in the subgroup analysis. Because actual numbers were not provided, it was not possible to evaluate further these stratified data (1). A reassuring finding is that, even in a population with such a high total calcium intake (Ϸ3 g/d), there was no significant difference between groups in the rate of urolithiasis during pregnancy or neonatal hypocalcemia (1).…”

Section: Disparities Between the 2 Largest Trialsmentioning

confidence: 99%

“…Our previous work on calcium supplementation during pregnancy is often discussed in the context of the results of a large, methodologically sound trial that was conducted by the National Institutes of Health (NIH) and published in the New England Journal of Medicine (1) and has formed the basis for systematic reviews (2,3). We would like to offer a few important clarifications concerning the interpretation of these findings.…”

Section: Introductionmentioning

confidence: 99%

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

Villar¹,

Belizán²

2000

The American Journal of Clinical Nutrition

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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.

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“…Several recent examples (5)(6)(7)(8) have been encountered where large randomized trials reached entirely different conclusions when compared with metaanalyses of earlier trials of small or even large sample size on the same question. For example, recent large trials seemed to invalidate our prior beliefs about the efficacy of treatments such as magnesium salts and nitrates for reducing overall mortality in acute myocardial infarction (9) or aspirin (10) and calcium supplementation (11) for the prevention of preeclampsia during pregnancy. Prior expectations of 30-60% reductions in mortality and preeclampsia, respectively, based on early trials, were not confirmed.…”

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confidence: 99%

Evolution of treatment effects over time: Empirical insight from recursive cumulative metaanalyses

Ioannidis¹

2001

Proceedings of the National Academy of Sciences

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Evidence on how much medical interventions work may change over time. It is important to determine what fluctuations in the treatment effect reported by randomized trials and their metaanalyses may be expected and whether extreme fluctuations signal future major changes. We applied recursive cumulative metaanalysis of randomized controlled trials to evaluate the relative change in the pooled treatment effect (odds ratio) over time for 60 interventions in two medical fields (pregnancy͞perinatal medicine, n ‫؍‬ 45 interventions; myocardial infarction, n ‫؍‬ 15 interventions). We evaluated the scatter of relative changes for different numbers of total patients in previous trials. Outlier cases were noted with changes greater than 2.5 standard deviations of the expected. With 500 accumulated patients, the pooled odds ratio may change by 0.6-to 1.7-fold in the immediate future. When 2000 patients have already been randomized, the respective figures are between 0.74-and 1.35-fold for pregnancy͞ perinatal medicine and between 0.83-and 1.21-fold for myocardial infarction studies. Extreme early fluctuations in the treatment effect were observed in three interventions (magnesium in myocardial infarction, calcium and antiplatelet agents for prevention of preeclampsia), where recent mega-trials have contradicted prior metaanalyses, as well as in four other examples where early large treatment effects were dissipated when more data appeared. Past experience may help quantify the uncertainty surrounding the treatment effects reported in early clinical trials and their metaanalyses. Early wide oscillations in the evolution of the treatment effect for specific interventions may sometimes signal further major changes in the future. mega-trials ͉ heterogeneity ͉ randomized trials R andomized trials and metaanalyses are often considered primary means for assessing the efficacy of medical interventions (1-4). However, clinical evidence evolves over time: new trials continue to be performed, replacing, updating, and supplementing the knowledge obtained from earlier ones. Heterogeneity (i.e., variability) among trial results is unavoidable. New trials may strengthen our prior beliefs about the magnitude of a treatment effect (i.e., how much a treatment works), or, in some cases, they may alter these beliefs or invalidate them. Several recent examples (5-8) have been encountered where large randomized trials reached entirely different conclusions when compared with metaanalyses of earlier trials of small or even large sample size on the same question. For example, recent large trials seemed to invalidate our prior beliefs about the efficacy of treatments such as magnesium salts and nitrates for reducing overall mortality in acute myocardial infarction (9) or aspirin (10) and calcium supplementation (11) for the prevention of preeclampsia during pregnancy. Prior expectations of 30-60% reductions in mortality and preeclampsia, respectively, based on early trials, were not confirmed.Important questions arise: Could we have anticipated th...

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Trial of Calcium to Prevent Preeclampsia

Abstract: Calcium supplementation during pregnancy did not prevent preeclampsia, pregnancy-associated hypertension, or adverse perinatal outcomes in healthy nulliparous women.

Cited by 551 publications

References 21 publications

Calcium supplementation in pregnancy and prevention of hypertensive disorders in elderly women

Calcium supplementation in pregnancy and prevention of hypertensive disorders in elderly women

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

Evolution of treatment effects over time: Empirical insight from recursive cumulative metaanalyses

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