Prepregnancy and early pregnancy calcium supplementation among women at high risk of pre-eclampsia: a multicentre, double-blind, randomised, placebo-controlled trial

Multicentre, parallel-arm, double-blind, randomized, placebo-controlled trial conducted in South Africa, Zimbabwe, and Argentina. Participants were adult (>=18 years), parous women whose previous pregnancy was complicated by preeclampsia or eclampsia and who intended to become pregnant; not currently pregnant at enrolment.

Calcium carbonate; 500 mg elemental calcium per day, taken as a chewable tablet, from prepregnancy randomisation until 20 weeks gestation; from 20 weeks gestation to birth, 1500 mg elemental calcium daily; tablets chewed in the evening, away from meals and iron supplements; no additional calcium supplements.

Calcium started before pregnancy and continued through early pregnancy did not significantly reduce recurrent preeclampsia compared with placebo (pre-eclampsia: 23% vs 29%; RR 0.80; p = 0.121). No significant differences in secondary outcomes. Per-protocol analysis with >=80% adherence suggested a potential reduction in pre-eclampsia (RR 0.66; 95% CI 0.44-0.98). Authors conclude that a small-to-moderate effect cannot be ruled out and that higher adherence may influence outcomes; overall, prepregnancy calcium did not produce a statistically significant reduction in recurrent preeclampsia in this high-risk population. Further research is warranted.

Trial powered to detect a large effect (≈40% reduction); may have missed small-to-moderate effects. Adherence varied, with potential benefit in those with high compliance. Open-label calcium after 20 weeks could dilute effects. Randomisation occurred before conception, with exposure limited to those who conceived and carried beyond 20 weeks. Generalisability may be limited to populations with low dietary calcium intake and prior preeclampsia; some misclassification and protocol deviations occurred (eight randomised in error).