Calcium supplementation for the prevention of pre‐eclampsia: Challenging the evidence from meta‐analyses
D. Wright, Alan Wright, Laura A. Magee, Peter von Dadelszen, K. H. Nicolaides
Abstract
Abstract Objective 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. Design 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. Setting Systematic review and meta‐analysis. Population 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). Methods We carried out a sensitivity analysis of evidence from the relevant Cochrane review, to examine the impact of study size. Main outcome measures pre‐eclampsia. Results 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 ( I 2 = 0). With inclusion of the smaller studies, mean RR decreased to 0.45 and I 2 increased to 70%. Conclusions 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.