We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 March 2013) and contacted study authors for more data where possible. We updated the search in May 2014 and added the results to the 'Awaiting Classification' section of the review.
SELECTION CRITERIA: We assessed eligibility and trial quality, extracted and double-entered data.
MAIN RESULTS: High-dose
calcium supplementation (≥1 g/day)We included 14 studies in the review, however one study contributed no data. We included 13 high-quality studies in our meta-analyses (15,730 women). The average risk of
high blood pressure (BP) was reduced with
calcium supplementation compared with placebo (12 trials, 15,470 women: risk ratio (RR) 0.65, 95% confidence interval (CI) 0.53 to 0.81; I² = 74%). There was also a significant reduction in the risk of
pre-eclampsia associated with
calcium supplementation (13 trials, 15,730 women: RR 0.45, 95% CI 0.31 to 0.65; I² = 70%). The effect was greatest for women with low
calcium diets (eight trials, 10,678 women: average RR 0.36, 95% CI 0.20 to 0.65; I² = 76%) and women at high risk of
pre-eclampsia (five trials, 587 women: average RR 0.22, 95% CI 0.12 to 0.42; I² = 0%). These data should be interpreted with caution because of the possibility of small-study effect or publication bias.The composite outcome
maternal death or serious morbidity was reduced (four trials, 9732 women; RR 0.80, 95% CI 0.65 to 0.97; I² = 0%).
Maternal deaths were not significantly different (one trial of 8312 women:
calcium group one death versus placebo group six deaths). There was an anomalous increase in the risk of HELLP (
haemolysis, elevated liver
enzymes and low platelets) syndrome (two trials, 12,901 women: RR 2.67, 95% CI 1.05 to 6.82; I² = 0%) in the
calcium group, however, the absolute number of events was low (16 versus six).The average risk of
preterm birth was reduced in the
calcium group (11 trials, 15,275 women: RR 0.76, 95% CI 0.60 to 0.97; I² = 60%) and amongst women at high risk of developing
pre-eclampsia (four trials, 568 women: average RR 0.45, 95% CI 0.24 to 0.83; I² = 60%), but no significant reduction in neonatal high care admission. There was no overall effect on the risk of
stillbirth or
infant death before discharge from hospital (11 trials 15,665 babies: RR 0.90, 95% CI 0.74 to 1.09; I² = 0%).One study showed a reduction in childhood systolic BP greater than 95th percentile among children exposed to
calcium supplementation in utero (514 children: RR 0.59, 95% CI 0.39 to 0.91). In a subset of these children,
dental caries at 12 years old was also reduced (195 children, RR 0.73, 95% CI 0.62 to 0.87). Low-dose
calcium supplementation (< 1 g/day)We included 10 trials (2234 women) that evaluated low-dose supplementation with
calcium alone (4) or in association with
vitamin D (3),
linoleic acid (2), or
antioxidants (1). Most studies recruited women at high risk for
pre-eclampsia, and were at high risk of bias, thus the results should be interpreted with caution. Supplementation with low doses of
calcium significantly reduced the risk of
pre-eclampsia (RR 0.38, 95% CI 0.28 to 0.52; I² = 0%). There was also a reduction in
hypertension, low
birthweight and neonatal intensive care unit admission.
AUTHORS' CONCLUSIONS:
Calcium supplementation (≥ 1 g/day) is associated with a significant reduction in the risk of
pre-eclampsia, particularly for women with low
calcium diets. The treatment effect may be overestimated due to small-study effects or publication bias. It also reduces
preterm birth and the occurrence of the composite outcome '
maternal death or serious morbidity'. We considered these benefits to outweigh the increased risk of
HELLP syndrome, which was small in absolute numbers. The World Health Organization recommends
calcium 1.5 g to 2 g daily for pregnant women with low
dietary calcium intake.The limited evidence on low-dose
calcium supplementation suggests a reduction in
pre-eclampsia, but needs to be confirmed by larger, high-quality trials. Pending such results, in settings of low
dietary calcium where high-dose supplementation is not feasible, the option of lower-dose supplements (500 to 600 mg/day) might be considered in preference to no supplementation.