Calcium supplementation for the prevention of pre-eclampsia: Challenging the evidence from meta-analyses.

Abstract

To investigate the validity of the conclusion from Cochrane reviews and meta-analyses that treatment with calcium supplementation during pregnancy reduces the risk for pre-eclampsia by 55%, which has been influential in international guidelines and future research. Sensitivity analysis of data from Cochrane reviews of trials evaluating high-dose calcium supplementation (of at least 1 g/day) for reduction of pre-eclampsia risk. Systematic review and meta-analysis. The Cochrane reviews and meta-analyses included 13 trials enrolling a total of 15 730 women. Random-effects meta-analysis of these studies resulted in a mean risk ratio (RR, calcium/placebo) of 0.45 (95% confidence interval [CI] 0.31-0.65; p < 0.0001). We carried out a sensitivity analysis of evidence from the relevant Cochrane review, to examine the impact of study size. pre-eclampsia. In the three largest studies, accounting for 13 815 (88%) of total recruitment, mean RR was 0.92 (95% CI 0.80-1.06) and there was no evidence of heterogeneity between studies (I² = 0). With inclusion of the smaller studies, mean RR decreased to 0.45 and I² increased to 70%. In assessment of the effect of calcium supplementation on pre-eclampsia risk, the naive focus on the mean of the random-effects meta-analysis in the presence of substantial heterogeneity is highly misleading.