Key messages
-
We found little to no difference in the number of women developing pre-eclampsia when they were given calcium during pregnancy, and we are uncertain about poor outcomes for mothers and babies.
-
Most participants started calcium in the middle 3 months of pregnancy, so we don't have information in this review about the effectiveness of calcium supplementation in very early pregnancy. We don't have information about women with enough calcium in their diet versus those who do not, nor those who are at high risk versus low risk of getting pre-eclampsia.
-
We found good evidence when we analysed only large studies, with more than 500 women. It is unlikely that further research would change the current evidence. Therefore, in future, research could focus on other ways to prevent blood pressure disorders during pregnancy.
Why is high blood pressure a problem during pregnancy?
High blood pressure in pregnancy is a leading cause of death and severe illness in mothers and babies. Pre-eclampsia is the most serious complication. It affects the placenta and can affect other organs, such as the kidneys, liver and brain. There is currently no treatment for pre-eclampsia apart from delivering the baby.
How might calcium help?
Some evidence suggests that calcium can lower blood pressure in people whose blood pressure is normal and in women who have had pre-eclampsia before, but other evidence does not support this. However, calcium is readily available, cheap and likely to be safe for mothers and babies. Calcium tablets are taken orally (swallowed). If calcium can prevent pre-eclampsia, it may reduce death and severe illness in mothers and babies.
What did we want to find out?
We wanted to know whether calcium is effective in preventing pre-eclampsia and other high blood pressure disorders when taken during pregnancy, and if it causes unwanted effects. We were also interested in whether calcium reduces the number of babies who die during or soon after birth, the number of mothers and babies who died or became ill, and babies who were born early.
What did we do?
We searched for studies that investigated calcium supplements during pregnancy. We used a checklist to make sure we only included studies that we could trust. We made judgements about the quality of the studies before comparing and summarising their results. Lastly, we rated our confidence in the findings.
What did we find?
We found 10 studies with 37,504 women that looked at the effects of calcium supplementation alongside standard care. Eight studies compared calcium supplementation to placebo (a dummy treatment), and two compared low-dose (500 mg daily) to high-dose (1500 mg daily) calcium supplementation. Studies took place worldwide, in high- and low-income countries. Some women in the studies had enough calcium in their diets and others did not. Some women were at high risk of pre-eclampsia and others weren't.
Calcium compared to placebo (8 studies, 15,504 women)
Evidence from 6 studies (15,364 women) showed that calcium may make little to no difference to pre-eclampsia compared to placebo. However, when we analysed only large studies with more than 500 women (4 studies, 14,730 women), we found strong evidence confirming that calcium makes little to no difference to pre-eclampsia compared to placebo.
Calcium probably results in little to no difference in the overall risk of a mother dying or developing severe complications of pre-eclampsia. It may result in little to no difference in death of the baby during pregnancy and early life.
We are very uncertain about the effect of calcium on the risk of mothers dying, on birth before 37 weeks, and also on unwanted effects.
Low- compared to high-dose calcium (2 studies, 22,000 women)
A lower dose of calcium may make little to no difference to pre-eclampsia compared to a higher dose. We are very uncertain about the effect of low-dose calcium on mothers dying compared to a higher dose. Taking a lower dose makes no difference to loss of the baby during pregnancy and early life, and probably makes little to no difference to birth before 37 weeks.
What are the limitations of the evidence?
Because most participants started calcium in the middle 3 months of pregnancy, we do not have information in this review about the effectiveness of calcium supplementation in very early pregnancy. This is the same for women who live in areas where people have enough calcium in their diet versus those who do not, and those who are at high risk versus low risk of getting pre-eclampsia.
How up to date is this evidence?
The evidence is current to January 2025.
Read the full abstract
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 strategy
We searched CENTRAL, MEDLINE, Embase, four other databases and two trials registries to 7 January 2025, and screened reference lists of retrieved studies and relevant systematic reviews.
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 placebo
Fourteen 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 treatment
Twelve 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 supplementation
We 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
Calcium supplementation versus placebo
Meta-analyses showed that calcium supplementation compared to placebo may result in little to no difference in pre-eclampsia, but we are very uncertain about its effect on preterm delivery before 37 weeks. However, high-certainty evidence from sensitivity analyses with only large trials (> 95% of participants in the main analyses), showed little to no difference in both pre-eclampsia and preterm delivery before 37 weeks. Maternal death was rare, so evidence about it is very uncertain.
Calcium supplementation probably results in little to no difference in the composite outcome maternal death or severe morbidity, may result in little to no difference in perinatal loss, and probably results in little to no difference in stillbirth. Evidence about adverse effects and neonatal death is very uncertain.
No trials measured neonatal death or severe morbidity.
Baseline calcium intake level and pre-eclampsia risk status did not impact our findings.
Low- versus high-dose calcium supplementation
Low- compared to high-dose calcium supplementation made no difference to outcomes in women at high risk for pre-eclampsia in low calcium-intake populations. Low-dose calcium supplementation may result in little to no difference in pre-eclampsia. Maternal death (5 per 10,000 women) was rare; the evidence is very uncertain. Low-dose calcium results in little to no difference in perinatal loss and stillbirth, and probably results in little to no difference in preterm delivery before 37 weeks. No trials measured severe maternal morbidity, neonatal death, severe neonatal morbidity, or adverse effects.
Funding
This review was part-funded by the World Health Organization.
Registration
Updated protocol (2024) PROSPERO: CRD42024623889
Review update (2018) DOI: 10.1002/14651858.CD001059.pub5
Original review (2002) DOI: 10.1002/14651858.CD001059
