Calcium supplementation does little to reduce pre-eclampsia risk

Initiating supplementation with calcium before or during pregnancy falls short of reducing the risk of pre-eclampsia, according to an individual participant data (IPD) meta-analysis.

Researchers searched multiple online databases for randomized controlled trials wherein pregnant people were assigned to receive calcium (at any dose, with or without additional supplements or treatments) or to placebo, aspirin, routine care, or no calcium supplementation. The intervention was started before or during pregnancy.

IPD were requested for all available maternal characteristics, details of the intervention, and all relevant maternal and perinatal outcomes. A total of seven trials for which IPD were shared were included in the meta-analysis. The population comprised 16,828 participants in total. The trials were conducted in Argentina, Egypt, Gambia, India, Iran, Mexico, Peru, South Africa, US, and Zimbabwe.

Pooled data showed no clear evidence of a reduction in the odds of pre-eclampsia (odds ratio [OR], 0.89, 95 percent confidence interval [CI], 0.73–1.07; p=0.43; five trials, n=14,763) or early-onset pre-eclampsia (OR, 0.90, 95 percent CI, 0.25–3.27; p=0·093; three trials, n=13,413) with calcium supplementation vs controls.

Gestational age at start of supplementation had a significant nonlinear interaction with treatment effects, such that when calcium supplementation was started at 10 weeks of gestation, the odds of pre-eclampsia appeared to be reduced by 35 percent compared with control (OR, 0.65, 95 percent CI, 0.48–0.90). Effects did not vary by participant-level (maternal age, BMI, parity, or maternal risk factors) or trial-level characteristics (population dietary calcium intake, calcium dose, adherence, or population risk status).

The findings demonstrate that calcium supplementation in pregnancy has limited benefit in terms of reducing the risk of pre-eclampsia. However, there is potential for calcium to prevent pre-eclampsia when started early in pregnancy, particularly in the first trimester.