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 1.5-2g/day calcium supplementation for low-intake pregnant women, based on randomised controlled trials of 1g/day calcium supplementation from 20weeks of gestation. This is problematic logistically in low-resource settings; excessive calcium may be harmful; and 20weeks 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, <1g/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 8-12weeks 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.