Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems.
Study Goal
The researchers aimed to assess the effects of calcium supplementation (including low-dose calcium with antioxidants) during pregnancy on hypertensive disorders and related maternal and child outcomes.
Results Summary
Low-dose calcium supplementation (including one trial with antioxidants) reduced the risk of pre-eclampsia and hypertension but had unclear effects on preterm birth and stillbirth. The evidence was limited by small sample sizes and high risk of bias in some trials.
Population
Pregnant women, particularly those at high risk for pre-eclampsia.
Effective Dosage
Low-dose calcium (< 1 g/day), with one trial combining calcium and antioxidants (specific dosage not detailed).
Duration
Duration varied by trial (not specified in abstract).
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
High-dose calcium supplementation (≥ 1 g/day) | decrease | risk of high blood pressure | women | RR 0.65, 95% CI 0.53 to 0.81 | reduced | #1 |
High-dose calcium supplementation (≥ 1 g/day) | decrease | risk of pre-eclampsia | women | average RR 0.45, 95% CI 0.31 to 0.65 | reduced | #2 |
High-dose calcium supplementation (≥ 1 g/day) | decrease | risk of pre-eclampsia | women with low calcium diets | average RR 0.36, 95% CI 0.20 to 0.65 | reduced | #3 |
High-dose calcium supplementation (≥ 1 g/day) | decrease | risk of pre-eclampsia | women at higher risk of pre-eclampsia | average RR 0.22, 95% CI 0.12 to 0.42 | reduced | #4 |
High-dose calcium supplementation (≥ 1 g/day) | decrease | composite outcome maternal death or serious morbidity | women | RR 0.80, 95% CI 0.66 to 0.98 | reduced | #5 |
High-dose calcium supplementation (≥ 1 g/day) | no change | maternal deaths | women | - | no different | #6 |
High-dose calcium supplementation (≥ 1 g/day) | increase | risk of HELLP syndrome | women | RR 2.67, 95% CI 1.05 to 6.82 | anomalous increase | #7 |
High-dose calcium supplementation (≥ 1 g/day) | decrease | average risk of preterm birth | women | RR 0.76, 95% CI 0.60 to 0.97 | reduced | #8 |
High-dose calcium supplementation (≥ 1 g/day) | decrease | risk of preterm birth | women at higher risk of developing pre-eclampsia | average RR 0.45, 95% CI 0.24 to 0.83 | reduced | #9 |
High-dose calcium supplementation (≥ 1 g/day) | no change | admission to neonatal intensive care | babies | - | no clear effect | #10 |
High-dose calcium supplementation (≥ 1 g/day) | no change | risk of stillbirth or infant death before discharge from hospital | babies | RR 0.90, 95% CI 0.74 to 1.09 | no clear effect | #11 |
High-dose calcium supplementation (≥ 1 g/day) | decrease | childhood systolic BP greater than 95th percentile | children exposed to calcium supplementation in utero | RR 0.59, 95% CI 0.39 to 0.91 | reduction | #12 |
High-dose calcium supplementation (≥ 1 g/day) | decrease | dental caries at 12 years old | children | RR 0.73, 95% CI 0.62 to 0.87 | reduced | #13 |
Low-dose calcium supplementation (< 1 g/day) | decrease | risk of pre-eclampsia | women | RR 0.38, 95% CI 0.28 to 0.52 | reduced | #14 |
Low-dose calcium supplementation (< 1 g/day) | decrease | high BP | women | RR 0.53, 95% CI 0.38 to 0.74 | reduction | #15 |
Low-dose calcium supplementation (< 1 g/day) | decrease | admission to neonatal intensive care unit | babies | RR 0.44, 95% CI 0.20 to 0.99 | reduction | #16 |
Low-dose calcium supplementation (< 1 g/day) | no change | preterm birth | women | average RR 0.83, 95% CI 0.34 to 2.03 | not reduced | #17 |
Low-dose calcium supplementation (< 1 g/day) | no change | stillbirth or death before discharge | babies | RR 0.48, 95% CI 0.14 to 1.67 | not reduced | #18 |
High-dose (≥ 1 g) calcium supplementation | decrease | risk of pre-eclampsia | women | RR 0.42, 95% CI 0.18 to 0.96 | reduced | #19 |
High-dose (≥ 1 g) calcium supplementation | no change | preterm birth | women | RR 0.31, 95% CI 0.09 to 1.08 | no differences | #20 |
High-dose (≥ 1 g) calcium supplementation | no change | eclampsia | women | RR 0.32, 95% CI 0.07 to 1.53 | no differences | #21 |
High-dose (≥ 1 g) calcium supplementation | no change | stillbirth | babies | RR 0.48, 95% CI 0.13 to 1.83 | no differences | #22 |
BACKGROUND: Pre-eclampsia and eclampsia are common causes of serious morbidity and death. Calcium supplementation may reduce the risk of pre-eclampsia, and may help to prevent preterm birth. This is an update of a review last published in 2014. OBJECTIVES: To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child outcomes. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (18 September 2017), and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs), including cluster-randomised trials, comparing high-dose calcium supplementation (at least 1 g daily of calcium) during pregnancy with placebo. For low-dose calcium we included quasi-randomised trials, trials without placebo, trials with cointerventions and dose comparison trials. DATA COLLECTION AND ANALYSIS: Two researchers independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two researchers assessed the evidence using the GRADE approach. MAIN RESULTS: We included 27 studies (18,064 women). We assessed the included studies as being at low risk of bias, although bias was frequently difficult to assess due to poor reporting and inadequate information on methods.High-dose calcium supplementation (≥ 1 g/day) versus placeboFourteen studies examined this comparison, however one study contributed no data. The 13 studies contributed data from 15,730 women to our meta-analyses. 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 reduction in the risk of pre-eclampsia associated with calcium supplementation (13 trials, 15,730 women: average RR 0.45, 95% CI 0.31 to 0.65; I² = 70%; low-quality evidence). This effect was clear for women with low calcium diets (eight trials, 10,678 women: average RR 0.36, 95% CI 0.20 to 0.65; I² = 76%) but not those with adequate calcium diets. The effect appeared to be greater for women at higher risk of pre-eclampsia, though this may be due to small-study effects (five trials, 587 women: average RR 0.22, 95% CI 0.12 to 0.42). These data should be interpreted with caution because of the possibility of small-study effects or publication bias. In the largest trial, the reduction in pre-eclampsia was modest (8%) and the CI included the possibility of no effect.The composite outcome maternal death or serious morbidity was reduced with calcium supplementation (four trials, 9732 women; RR 0.80, 95% CI 0.66 to 0.98). Maternal deaths were no different (one trial of 8312 women: one death in the calcium group versus six in the placebo group). There was an anomalous increase in the risk of HELLP syndrome in the calcium group (two trials, 12,901 women: RR 2.67, 95% CI 1.05 to 6.82, high-quality evidence), however, the absolute number of events was low (16 versus six).The average risk of preterm birth was reduced in the calcium supplementation group (11 trials, 15,275 women: RR 0.76, 95% CI 0.60 to 0.97; I² = 60%; low-quality evidence); this reduction was greatest amongst women at higher risk of developing pre-eclampsia (four trials, 568 women: average RR 0.45, 95% CI 0.24 to 0.83; I² = 60%). Again, these data should be interpreted with caution because of the possibility of small-study effects or publication bias. There was no clear effect on admission to neonatal intensive care. There was also no clear 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).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) versus placebo or no treatmentTwelve trials (2334 women) evaluated low-dose (usually 500 mg daily) supplementation with calcium alone (four trials) or in association with vitamin D (five trials), linoleic acid (two trials), or antioxidants (one trial). 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 reduced the risk of pre-eclampsia (nine trials, 2234 women: RR 0.38, 95% CI 0.28 to 0.52). There was also a reduction in high BP (five trials, 665 women: RR 0.53, 95% CI 0.38 to 0.74), admission to neonatal intensive care unit (one trial, 422 women, RR 0.44, 95% CI 0.20 to 0.99), but not preterm birth (six trials, 1290 women, average RR 0.83, 95% CI 0.34 to 2.03), or stillbirth or death before discharge (five trials, 1025 babies, RR 0.48, 95% CI 0.14 to 1.67).High-dose (=/> 1 g) versus low-dose (< 1 g) calcium supplementationWe included one trial with 262 women, the results of which should be interpreted with caution due to unclear risk of bias. Risk of pre-eclampsia appeared to be reduced in the high-dose group (RR 0.42, 95% CI 0.18 to 0.96). No other differences were found (preterm birth: RR 0.31, 95% CI 0.09 to 1.08; eclampsia: RR 0.32, 95% CI 0.07 to 1.53; stillbirth: RR 0.48, 95% CI 0.13 to 1.83). AUTHORS' CONCLUSIONS: High-dose calcium supplementation (≥ 1 g/day) may reduce the risk of pre-eclampsia and preterm birth, particularly for women with low calcium diets (low-quality evidence). The treatment effect may be overestimated due to small-study effects or publication bias. It reduces the occurrence of the composite outcome 'maternal death or serious morbidity', but not stillbirth or neonatal high care admission. There was an increased risk of HELLP syndrome with calcium supplementation, which was small in absolute numbers.The limited evidence on low-dose calcium supplementation suggests a reduction in pre-eclampsia, hypertension and admission to neonatal high care, but needs to be confirmed by larger, high-quality trials.