Low-dose calcium supplementation for preventing pre-eclampsia: a systematic review and commentary

Background: Epidemiological data link low dietary calcium with pre-eclampsia. Current recommendations are for 1.5-2 g/day calcium supplementation for low-intake pregnant women, based on randomised controlled trials of ≥1 g/day calcium supplementation from 20 weeks of gestation. This is problematic logistically in low-resource settings; excessive calcium may be harmful; and 20 weeks may be too late to alter outcomes.

Objectives: To review the impact of lower dose calcium supplementation on pre-eclampsia risk.

Search strategy and selection criteria: We searched PubMed and the Cochrane Pregnancy and Childbirth Group trials register.

Data collection and analysis: Two authors extracted data from eligible randomised and quasi-randomised trials of low-dose calcium (LDC, <1 g/day), with or without other supplements.

Main results: Pre-eclampsia was reduced consistently with LDC with or without co-supplements (nine trials, 2234 women, relative risk [RR] 0.38; 95% confidence interval [95% CI] 0.28-0.52), as well as for subgroups: LDC alone (four trials, 980 women, RR 0.36; 95% CI 0.23-0.57]); LDC plus linoleic acid (two trials, 134 women, RR 0.23; 95% CI 0.09-0.60); LDC plus vitamin D (two trials, 1060 women, RR 0.49; 0.31-0.78) and a trend for LDC plus antioxidants (one trial, 60 women, RR 0.24; 95% CI 0.06-1.01). Overall results were consistent with the single quality trial of LDC alone (171 women, RR 0.30; 95% CI 0.06-1.38). LDC plus antioxidants commencing at 8-12 weeks tended to reduce miscarriage (one trial, 60 women, RR 0.06; 95% CI 0.00-1.04).

Conclusions: These limited data are consistent with LDC reducing the risk of pre-eclampsia; confirming this in sufficiently powered randomised controlled trials would have implications for current guidelines and their global implementation.