Abstract
Background:
Calcium supplementation reduces the risk of pre-eclampsia, but questions remain about the dosage to prescribe and who would benefit most.
Objective:
To evaluate the effectiveness of high- (≥1 g/d) and low-dose (<1 g/d) calcium for pre-eclampsia prevention, and according to baseline dietary calcium, pre-eclampsia risk, and co-interventions, and intervention timing.
Search strategy:
CENTRAL, PubMed, Global Index Medicus, and CINAHL from inception to Feb/2/2021, clinical trial registries, reference lists, and expert input (CRD42018111239).
Selection criteria:
Randomised controlled trials of calcium supplementation for pre-eclampsia prevention, for women before or during pregnancy. Network meta-analysis (NMA) also included trials of different calcium doses.
Data collection and analysis:
Two independent reviewers extracted published data. The meta-analysis employed random effects models, and the NMA, a Bayesian random-effects model to obtain direct and indirect effect estimates.
Main results:
The meta-analysis included 30 trials (n=20,445 women), and the NMA to evaluate calcium dosage included 25 trials (n=15,038). Calcium supplementation prevented pre-eclampsia similarly in high (risk ratio 0.49 [0.36-0.66]) or low dose (risk ratio 0.49 [0.36-0.65]). By NMA, high- (vs. low-) dose calcium did not differ in effect (risk ratio 0.79 [0.43-1.40]). Calcium was similarly effective regardless of baseline pre-eclampsia risk, vitamin D co-administration, or timing of calcium initiation, but calcium was ineffective among women with adequate average baseline calcium intake.
Conclusions:
Low- and high-dose calcium supplementation are effective for pre-eclampsia prevention in women with low calcium intake. This has implications for population-level implementation where dietary calcium is low, and targeted implementation where average intake is adequate.
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