Calcium supplementation (other than for preventing or treating hypertension) for improving pregnancy and infant outcomes

Pranom Buppasiri, Pisake Lumbiganon, Jadsada Thinkhamrop, Chetta Ngamjarus, Malinee Laopaiboon, Nancy Medley

Maternal nutrition during pregnancy is known to have an effect on fetal growth and development. It is recommended that women increase their calcium intake during pregnancy and lactation, although the recommended dosage varies among professionals. Currently, there is no consensus on the role of routine calcium supplementation for pregnant women other than for preventing or treating hypertension. To determine the effect of calcium supplementation on maternal, fetal and neonatal outcomes (other than for preventing or treating hypertension) as well as any possible side effects. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30th September 2014). We considered all published, unpublished and ongoing randomised controlled trials (RCTs) comparing maternal, fetal and neonatal outcomes in pregnant women who received calcium supplementation versus placebo or no treatment. Cluster-RCTs were eligible for inclusion but none were identified. Quasi-RCTs and cross-over studies were not eligible for inclusion. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Twenty-five studies met the inclusion criteria, but only 23 studies contributed data to the review. These 23 trials recruited 18,587 women, with 17,842 women included in final analyses. There were no statistically significant differences between women who received calcium supplementation and those who did not in terms of reducing preterm births less than 37 weeks' gestation (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.70 to 1.05; 13 studies, 16,139 women; random-effects model) or less than 34 weeks' gestation (RR 1.04, 95% CI 0.80 to 1.36; four trials, 5669). Most studies were of low risk of bias. We conducted sensitivity analysis for the outcome of preterm birth less than 37 weeks by removing two trials with unclear risk of bias for allocation concealment; the results then favoured treatment with calcium supplementation (RR 0.80, 95% CI 0.65 to 0.99; 11 trials, 15,379 women). There was no significant difference in infant low birthweight between the two treatment groups (RR 0.93, 95% CI 0.81 to 1.07; six trials, 14,162 infants; random-effects model). However, when compared to the control group, women in the calcium supplementation group gave birth to slightly heavier birthweight infants (mean difference 56.40, 95% CI 13.55 to 99.25; 21 trials, 9202 women; random-effects model).Three outcomes were chosen for assessment with the GRADE software: preterm birth less than 37 weeks; preterm birth less than 34 weeks; and low birthweight less than 2500 g. Evidence for these outcomes was assessed as of moderate quality. This review indicates that there are no clear additional benefits to calcium supplementation in prevention of preterm birth or low infant birthweight. While there was a statistically significant difference of 56 g identified in mean infant birthweight, there was significant heterogeneity identified, and the clinical significance of this difference is uncertain.