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Calcium supplementation for the prevention of pre-eclampsia: Challenging the evidence from meta-analyses
David Wright1, Alan Wright1, Laura A Magee2
1Institute of Health Research, University of Exeter, Exeter, UK.
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 (I2 = 0). With inclusion of the smaller studies, mean RR decreased to 0.45 and I2 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.
