Dietary calcium supplementation for prevention of pre‐eclampsia and related problems: a systematic review and commentary

BACKGROUND: Calcium supplementation during pregnancy may reduce the risk of hypertensive disorders of pregnancy. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Central Register of Controlled Trials (March 2006). SELECTION CRITERIA: Randomised trials comparing at least 1 g of calcium daily during pregnancy with placebo. Eligibility and trial quality were assessed. DATA COLLECTION AND ANALYSIS: Data were extracted and analysed using Review Manager software. MAIN RESULTS: Twelve studies (15,528 women) were included, all of good quality. Most women were at low risk and had low dietary calcium. High blood pressure was reduced with calcium supplementation rather than placebo (11 trials, 14,946 women: relative risk RR random effects model 0.70; 95% CI 0.57-0.86), as was pre-eclampsia (12 trials, 15,206 women: RR 0.48; 95% CI 0.33-0.69). The effect was greatest for women at high risk (five trials, 587 women: RR 0.22; 95% CI 0.12-0.42) and for those with low baseline calcium intake (seven trials, 10,154 women: RR 0.36; 95% CI 0.18-0.70). There was heterogeneity, with less effect in the larger trials. The composite outcome maternal death or serious morbidity was reduced (four trials, 9732 women: RR 0.80; 95% CI 0.65-0.97). The syndrome of haemolysis, elevated liver enzymes and low platelets was increased (two trials, 12,901 women: RR 2.67; 95% CI 1.05-6.82). There was no overall effect on the risk of preterm birth or stillbirth or death before discharge from hospital. CONCLUSIONS: Calcium supplementation appears to reduce the risk of pre-eclampsia and to reduce the rare occurrence of the composite outcome 'maternal death or serious morbidity'. There were no other clear benefits or harms. COMMENTARY: We present the hypothesis that adequate dietary calcium before and in early pregnancy may be needed to prevent the underlying pathology responsible for pre-eclampsia. We suggest that the research agenda be redirected towards calcium supplementation at a community level.