Who randomized trial of calcium supplementation among low calcium intake pregnant women


      To determine if calcium supplementation to low calcium intake pregnant women reduces the incidence of preeclampsia.

      Study design

      First we verified systematic reviews of randomised trials of prenatal calcium supplementation that suggested such treatment prevents preeclampsia, when dietary calcium intake is deficient. Then a randomized, double blinded trial was conducted through the World Health Organization collaborating institutions in Argentina, Egypt, India, Peru, South Africa and Vietnam, in populations with mean dietary calcium intake <600 mg/day. Nulliparous normotensive women received either 1.5g Ca/day or placebo throughout pregnancy starting before week 20. Primary outcomes were preeclampsia and preterm delivery, secondary were eclampsia, gestational hypertension. After the trial a secondary analysis of composite outcomes stressing severity was performed.


      8,325 women were randomised. Both groups had similar gestational age and demographic characteristics at entry. Compliance (both 85%) and follow-up loss rates were similar (calcium 3.4%, placebo 3.7%). Supplementation was associated with a reduction in preeclampsia starting at gestational week 32, most evident by 35 weeks (p=0.04), but these changes failed to achieve significance in the overall sample. However reduction in severe preeclamptic complications did (RR=0.76; 95%CI 0.66-89). Eclampsia and severe gestational hypertension were significantly lower as were adverse outcomes measured through a composite index of severe maternal morbidity and mortality (RR=0.80; 95%CI 0.70-0.91), and neonatal death (RR=0.70; 95%CI 0.56-0.88). In a stratified analysis, preterm delivery was only reduced in women <20 years of age (RR=0.82; 95%CI 0.67-1.01).


      A 1.5g calcium/day supplement started before midpregnancy may prevent preeclampsia, but most importantly reduces its severity and maternal and/or neonatal morbidity and mortality in low calcium intake women. An easily implemented intervention could prevent preeclampsia-associated morbidity and mortality especially in developing countries.