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Keywords:

  • Calcium;
  • pregnancy;
  • preeclampsia;
  • eclampsia;
  • birthweight;
  • preterm birth;
  • urolithiasis

Abstract

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Comments
  6. Conflicts of interests
  7. References
  8. Appendix
  9. Supporting Information

Gestational hypertensive disorders are the second leading cause of maternal death worldwide. Epidemiological and clinical studies have shown that an inverse relationship exists between calcium intake and development of hypertension in pregnancy. The purpose of this review was to evaluate preventive effect of calcium supplementation during pregnancy on gestational hypertensive disorders and related maternal and neonatal morbidity and mortality. A literature search was carried out on PubMed, WHOLIS, PAHO and Cochrane Library. Only randomised trials were included in the review. Data were extracted into a standardised Excel sheet. Primary outcomes were pre-eclampsia, preterm birth and birthweight. Other neonatal outcomes such as neonatal mortality, small-for-gestational age and low birthweight were also evaluated. A total of 15 randomised controlled trials were included in this review. Pooled analysis showed that calcium supplementation during pregnancy reduced risk of pre-eclampsia by 52% [relative risk (RR) 0.48; 95% confidence interval (CI) 0.34, 0.67] and that of severe pre-eclampsia by 25% (RR 0.75 [95% CI 0.57, 0.98]). There was no effect on incidence of eclampsia (RR 0.73 [95% CI 0.41, 1.27]). There was a significant reduction for risk of maternal mortality/severe morbidity (RR 0.80 [95% CI 0.65, 0.97]). Calcium supplementation during pregnancy was also associated with a significant reduction in risk of pre-term birth (RR 0.76 [95% CI 0.60, 0.97]). There was an extra gain of 85 g in the intervention group compared with control (mean difference 85 g [95% CI 37, 133]). There was no effect of calcium supplementation on perinatal mortality (RR 0.90 [95% CI 0.74, 1.09]). There was a statistically non-significant increased risk of urolithiasis in the intervention group compared with control (RR 1.52 [95% CI 0.06, 40.67]). In conclusion, calcium supplementation during pregnancy is associated with a reduction in risk of gestational hypertensive disorders and pre-term birth and an increase in birthweight. There is no increased risk of kidney stones.

Hypertensive disorders of pregnancy are an important cause of maternal morbidity and mortality especially in developing countries.1 It is the second major cause of maternal deaths worldwide and the number one cause of maternal death in Latin America and Caribbean.1 Hypertensive disorders of pregnancy include a group of conditions associated with high blood pressure and/or proteinuria and in some cases convulsions.2 The most serious consequences for the mother and the baby result from pre-eclampsia and eclampsia.3 The pathophysiology of pre-eclampsia is related to placental hypoxia that leads to release of anti-angiogenic factors, which in turn leads to vasospasm, pathologic vascular lesions in multiple organ systems, increased platelet activation and subsequent activation of the coagulation system in the micro-vasculature.4–6 Eclampsia presents clinically in the form of seizures which often leave the patient unconscious and if left untreated may lead to death.5

Epidemiological and clinical studies have shown that an inverse relationship exists between calcium intake and development of hypertension in pregnancy.7,8 Many trials have been conducted to assess the preventive effect of calcium supplementation for hypertensive disorders in pregnancy.9 There is substantial evidence that supports that calcium supplementation in pregnancy is associated with a reduction in gestational hypertensive disorders,10,11 although the impact varies according to the baseline calcium intake of the population and pre-existing risk factors.9,12 A Cochrane review2 that included 13 randomised trials comprising 15 730 women has shown that calcium supplementation during pregnancy reduces the incidence of pre-eclampsia by 55% [relative risk (RR) 0.45; 95% confidence interval (CI) 0.31, 0.65] and that of gestational hypertension by 35% (RR 0.65 [95% CI 0.53, 0.81]). A review by our team for Live Saved Tool (LiST) model13 included studies from developing countries only and our results showed that calcium supplementation reduces the incidence of pre-eclampsia by 59% (RR 0.41 [95% CI 0.24, 0.69]) and that of gestational hypertension by 45% (RR 0.55 [95% CI 0.36, 0.85]). Another review by Trumbo et al. had shown that beneficial effects of calcium supplementation cannot be generalised to USA populations and suggested that beneficial effects may only be shown for populations with low baseline calcium intake.12

In the above-mentioned reviews, the main focus of investigation was to look at the preventive effect of calcium supplementation for gestational hypertensive disorders. It is however not well investigated that how calcium supplementation affects birth outcomes. For example, it has been shown that calcium supplementation during pregnancy reduces incidence of preterm birth.2,14 Does this prevention of prematurity increase birthweight? Does it increase neonatal survival? Does it reduce severe morbidity in the neonatal period, for example admission to the intensive care unit? The potential side effects of calcium supplementation, for example proposed increased risk of urolithiasis, have also not been evaluated before. The objective of this review was to assess the effect of calcium supplementation during pregnancy for prevention of gestational hypertensive disorders and also to look at birth and maternal outcomes not evaluated before and to evaluate occurrence of any side effects.

Methods

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Comments
  6. Conflicts of interests
  7. References
  8. Appendix
  9. Supporting Information

Searches

An electronic search was conducted on PubMed, Cochrane Library, WHOLIS and PAHO to look for studies relating calcium supplementation with gestational hypertensive related disorders. The search strategies used for these databases are given in Appendix 1. The search was limited to ‘randomised trial’ and ‘humans’. Studies were considered for inclusion irrespective of language of publication. Additional studies were obtained through hand search of references from identified studies and previous reviews.

Inclusion/exclusion criteria

  • • 
    Only randomised controlled trials were considered for inclusion in the review. Studies with quasi-experimental design were excluded.
  • • 
    Calcium supplementation (in the form of oral supplements) started before 32 weeks of pregnancy at the latest.
  • • 
    Those studies were excluded where interventions were to improve dietary intake of calcium and no oral supplements was given.
  • • 
    Those studies were excluded where calcium was supplemented as a therapeutic intervention for gestational hypertensive disorders and not as a preventive measure.
  • • 
    The comparison group was supplemented either with placebo or simply observed as controls (no intervention).

Quantitative data synthesis

The primary outcomes assessed were pre-eclampsia, preterm birth and birthweight. Data on neonatal and other maternal outcome were also collected. Pooled analyses were conducted where data were available from more than one study for an outcome. The pooled results were presented as relative risk (RRs) and 95% confidence intervals (CIs). The assessment of statistical heterogeneity among trials was done by visual inspection, that is, the overlap of the confidence intervals among the studies, and by the chi-square (P-value) of heterogeneity in the meta-analyses. A low P-value (<0.10) or a large chi-squared statistic relative to its degree of freedom was considered as providing evidence of heterogeneity. The I2 values were inspected and values >50% were taken as evidence of substantial statistical heterogeneity. In situations of substantial heterogeneity being present, causes were explored by sensitivity analysis and random effects model were used. Funnel plots were drawn to assess publication bias when pooled studies exceed ten in number for an outcome. The quality of overall evidence for primary outcomes was assessed by GRADE criteria15 and findings were presented in a ‘summary of findings table’. We did two a priori subgroup analysis; low baseline calcium intake (<900 mg/day) vs. adequate calcium (>900 mg/day) intake and; developing countries vs. developed countries. The developing countries were defined as countries with Gross National Income per capita below US$11 905, according to World Bank.16 All analyses were conducted using software RevMan version 5.17

Results

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Comments
  6. Conflicts of interests
  7. References
  8. Appendix
  9. Supporting Information

Trial flow

A total of 4260 titles were identified by searches conducted on all databases (Figure 1). Initially, 29 studies were considered for inclusion in the review. Out of these, seven studies were excluded because of insufficient data on outcomes of interest.18–24 Three studies were excluded because of very low grade quality.25–27 In two trials, calcium was supplemented as a treatment of gestational hypertensive disorder and not as a preventive measure.28,29 Two studies were excluded because calcium was supplemented in combination, either with linoleic acid30 or L-aspartate,31 and it was not possible to separate the specific effect of calcium supplementation. Finally, 15 studies that met our inclusion criteria were included in the review.32–46

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Figure 1. Flow diagram for identification of studies evaluating calcium supplementation during pregnancy.

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Study characteristics

All the studies included in the analyses were randomised controlled trials with a comparison group receiving a placebo or no intervention. Table 1 presents characteristics of included studies. The starting period of calcium supplementation in all the included studies was before 20–32 weeks of gestation and continued till delivery. In three of the included studies,36,39,40,42 the participants were defined as being at a higher risk of developing hypertension in pregnancy (pregnant teenage girls, women with previous pre-eclampsia or women with positive roll over test) compared with the general population. The dose of calcium ranged from 0.5 to 2 g/day. Five of the studies included were from Asia,38,42,43,45,46 four from USA,33–36 four from South America37,39–41 and one from Australia.32 In addition, one large multicentre trial was conducted by World Health Organization (WHO) in Argentina, Egypt, India, Peru, South Africa and Vietnam.44 Table S1 presents risk of bias according to the latest Cochrane handbook.

Table 1.  Characteristics of included studies
Study (reference)CountryTarget populationBaseline calcium intake as low (<900 mg/day), or adequate (>900 mg/day)Dose of supplementation (cumulative dose)Duration of supplementation
Belizan et al 199137ArgentinaNulliparous pregnant women, <20 weeks of gestation. No co-morbidityLow2 g/day<20 weeks of pregnancy till delivery
Kumar et al 200938IndiaPrimigravida women with gestational age between 12–25 weeksLow2 g/day12–25 weeks of pregnancy till delivery
Lopez-Jaramillo et al. 198941EcuadorNulliparous pregnant women, <24 weeks of gestation. No co-morbidityLow2 g/day23 weeks of pregnancy till delivery
Lopez-Jaramillo et al. 199040EcuadorNulliparous pregnant women in 28–30 weeks of gestation with positive roll over testLow2 g/day28–30 weeks of pregnancy till delivery
Lopez-Jaramillo et al. 199739EcuadorTeenage (<17.5 years) Nulliparous pregnant women <20 weeks of gestation. No co-morbidities or addictionLow2 g/day20 weeks of pregnancy till delivery
Niromanesh et al. 200142Turkey28–32 weeks pregnant women with positive roll over test and with at least one risk factor for pre-eclampsia. No chronic medical conditionNot specified2 g/day28–32 weeks of pregnancy till delivery
Purwar et al. 199643IndiaNulliparous pregnant women <20 weeks of gestation. No co-morbidityLow2 g/day20 weeks of pregnancy till delivery
Villar et al. 200644Multicentre trial (Argentina, Egypt, India, Peru, South Africa and Vietnam)Primiparous women <20 weeks of gestation. No co-morbiditiesLow1.5 g/dayFrom enrolment (< 20 weeks) till delivery
Taherian et al. 200246IranNulliparous pregnant women <20 weeks of gestation. No co-morbiditiesLow500 mg/dayFrom enrolment (< 20 weeks) till delivery
Wanchu et al. 200145IndiaNulliparous pregnant women <20 weeks of gestation. No known co-morbiditiesLow2 g/dayFrom enrolment (< 20 weeks) till delivery
Crowther et al. 199932AustraliaNulliparous women; singleton pregnancy; <24 weeks of gestation; blood pressure <140/90 mmHg; expected to give birth at a collaborating centreAdequate1.8 g/dayFrom 20–24 weeks until birth
Levine et al. 199733USAPregnant nulliparous; blood pressure 134/84 mmHg or less; urine protein dipstick negative or trace; 13–21 weeks of pregnantAdequate2 g/dayFrom 31–21 weeks pregnancy till delivery
Sanchez-Ramos et al. 199434USANormotensive nulliparae; positive roll-over test and positive angiotensin II infusion test at 20–24 weeks’ gestation.Low2 g/dayFrom 20–24 weeks of pregnancy till delivery
Villar et al. 198735USANulliparous or primiparous; known menstrual dates; age 18–30 years; singleton pregnancy; negative roll-over testAdequate1.5 g/dayFrom 26 weeks’ pregnancy till delivery
Villar and Repke 199036USAPregnant women 17 years or youngerAdequate2 g/dayFrom enrolment till delivery

Quantitative data synthesis

Fifteen studies reported data on the effect of calcium supplementation during pregnancy on risk of pre-eclampsia.32–46 The pooled analysis showed a reduction of 52% in the intervention group compared with the control group (RR 0.48 [95% CI 0.34, 0.67]). On visual inspection of the forest plot, six of the included studies showed a clear benefit (Figure 2). There was a substantial heterogeneity in the pooled data (I2 = 70), so random effects models were used. The reduction was more marked in women with low calcium intake (RR 0.42 [95% CI 0.26, 0.69]) compared with women with adequate calcium intake (RR 0.62 [95% CI 0.32, 1.20]). Five studies reported data on incidence of severe pre-eclampsia33,34,44–46 and the pooled results showed a statistically significant reduction of 25% in the intervention group compared with control (RR 0.75 [95% CI 0.57, 0.98]) (Figure 3).

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Figure 2. Effect of calcium supplementation during pregnancy on incidence of pre-eclampsia.

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Figure 3. Effect of calcium supplementation during pregnancy on incidence of severe pre-eclampsia.

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Data on preterm births were included from 11 trials32–40,43,44 and the pooled analysis showed a significant reduction of 24% (RR 0.76 [95% CI 0.60, 0.97]) in the intervention group compared with the control group (Figure 4). Risk of low birthweight was reported by six studies32,33,36–38,44 and analyses showed a reduction of 15% (RR 0.85 [95% CI 0.72, 1.01]) following calcium supplementation. However, the results were statistically non-significant (Figure 5). Thirteen studies reported data on birthweight and pooled effect size showed an extra gain of 85 g in the intervention group compared with control (Figure 6). Data from seven studies did not show a statistically significant effect of calcium supplementation on incidence of small-for-gestational-age babies (Figure 7). There was no significant effect on incidence of perinatal mortality in the intervention group compared with control (Figure 8). Pooled results from two studies showed that there is no significant increased risk of urolithiasis or renal colic (RR 1.75 [95% CI 0.51, 5.99] and RR 1.52 [95% CI 0.06, 40.67], respectively) in the calcium-supplemented group compared with placebo. Table 2 shows some other maternal and neonatal outcomes evaluated in this review. Table 3 gives results of subgroup analysis; developed countries vs. developing countries. Table 4 presents a summary of finding table according to the GRADE criteria for selected outcome.

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Figure 4. Effect of calcium supplementation during pregnancy on incidence of preterm birth.

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Figure 5. Effect of calcium supplementation during pregnancy on incidence of low birthweight babies.

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Figure 6. Effect of calcium supplementation during pregnancy on birthweight (g).

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Figure 7. Effect of calcium supplementation during pregnancy on incidence of small-for-gestational-age babies.

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Figure 8. Effect of calcium supplementation during pregnancy on incidence on perinatal mortality.

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Table 2.  Summary estimates of other maternal and neonatal outcomes
OutcomeNo. of studiesNo. of participantsSummary estimate, RR [95% CI]Fixed/random model
  • a

    Include any one of the following; admission to intensive or special care unit, eclampsia, severe pre-eclampsia, placental abruption, HELLP (haemolysis, elevated liver enzyme and low platelet count) syndrome, renal failure or maternal death.

  • PPROM, preterm premature rupture of membrane; NICU, neonatal intensive care unit; RR, relative risk; NA, not applicable.

Eclampsia313 4250.73 [0.41, 1.27]Fixed
Maternal death/severe morbiditya297320.80 [0.65, 0.97]Fixed
Maternal mortality170.17 [0.02, 0.76]NA
Induction of labour560400.91 [0.81, 1.03]Fixed
PPROM250450.76 [0.22, 2.67]Random
Neonatal mortality212 4981.07 [0.39, 2.95]Random
NICU admissions357501.09 [0.96, 1.24]Fixed
Urolithiasis212 9011.52 [0.06, 40.67]Random
Renal colic212 9011.75 [0.51, 5.99]Fixed
Table 3.  Subgroup analysis for developed countries vs. developing countries
OutcomeDeveloped countriesDeveloping countries
No. of studiesEffect size, RR [95% CI]No. of studiesEffect size, RR [95% CI]
  1. RR, relative risk; MD, mean difference.

Pre-eclampsia50.52 [0.27, 1.00]100.41 [0.24, 0.69]
Preterm birth50.63 [0.33, 1.19]60.79 [0.59, 1.05]
Perinatal mortality51.08 [0.65, 1.82]60.87 [0.70, 1.07]
Birthweight (g)3MD = 35.77 [−65.33, 136.88]10MD = 94.23 [49.97, 138.49]
Low birthweight30.59 [0.31, 1.13]30.95 [0.85, 1.05]
Small-for-gestational age21.16 [0.90, 1.49]50.85 [0.65, 1.12]
Table 4.  Quality assessment of calcium supplementation during pregnancy on maternal and neonatal outcomes
No. of studiesStudy designLimitationsConsistencyGeneralisability to population of interestGeneralisability to intervention of interestCalciumControlRelative risk [95% CI]
  1. RCT, randomised controlled trial.

Outcome: pre-eclampsia: quality of evidence: moderate
15RCTsTwo of the pooled studies did not have a placebo group and the comparison group was simply observed as control45,46Significant heterogeneity (I2 = 70%)10 studies from developing countries and 5 studies from developed countriesYes3985430.48 [0.34, 0.67]
Five studies showing a clear benefit
Outcome: severe pre-eclampsia: quality of evidence: moderate
5RCTsTwo of the included studies did not have a placebo groupNo heterogeneity (I2 = 0%)2 studies from developed countries and one from developing countriesYes891200.75 [0.57, 0.98]
Outcome: gestational hypertension: quality of evidence: moderate
12RCTsNoneHeterogeneity (I2 = 74%)5 studies from developed countries and 7 from developing countriesYes126014720.65 [0.53, 0.81]
Four studies showing a clear benefit
Outcome: preterm birth: quality of evidence: moderate
11RCTsAllocation concealment was unclear in one study40Significant heterogeneity (I2 = 60%)4 studies from developed countries and 7 from developing countriesYes7227950.76 [0.60, 0.97]
Outcome: birthweight (g):quality of evidence: moderate
13RCTsTwo of the pooled studies did not have a placebo group but the comparison group was simply observed as controlsSignificant heterogeneity (I2 = 89%)3 studies from developed countries and 10 from developing countries.YesMean difference 85.75 [37.91, 133.58]
Outcome: small-for-gestational age: quality of evidence: moderate
7RCTsTwo of the pooled studies did not have a placebo group but the comparison group was simply observed as controlsNo heterogeneity (I2 = 0%)2 studies from developed countries and 5 from developing countries.Yes2182151.01 [0.84, 1.21]
Outcome: low birthweight (<25 00 g): quality of evidence: moderate
6RCTsNoneSignificant heterogeneity (I2 = 50%)2 studies from developed countries and 4 studies from developing countriesYes8108780.85 [0.72, 1.01]
Random model used

Comments

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Comments
  6. Conflicts of interests
  7. References
  8. Appendix
  9. Supporting Information

The role of calcium supplementation for prevention of gestational hypertensive disorders has been evaluated in several studies in recent years. The review by Hofmeyr et al.2 included studies from both developed and developing countries, and their pooled estimate had shown that calcium supplementation during pregnancy significantly reduced occurrence of gestational hypertension (RR 0.65 [95% 0.53, 0.81]); pre-eclampsia (RR 0.45 [95% CI 0.31, 0.65]) and preterm birth (RR 0.76 [95% CI 0.60, 0.97]). Another review by our team14 for LiST included studies from developing countries only and our results showed that calcium supplementation during pregnancy reduced risk of gestational hypertension by 45% (RR 0.55 [95% CI 0.36, 0.85]) and that of pre-eclampsia by 59% (RR 0.41 [95% CI 0.24, 0.69]). There was also a significant reduction in risk of pre-term birth (RR 0.88 [95% CI 0.78, 0.99]). On the other hand, a review by Trumbo and Ellwood for the US Food and Drug Administration (FDA) has shown that the beneficial effects of calcium supplementation during pregnancy cannot be generalised to populations with adequate calcium intake and suggested that effect lies only for populations with low calcium intake.12 This conclusion was based on critical evaluation of studies conducted in similar setting as that of USA; however, no meta-analysis was performed.

The findings of our current analysis are broadly confirmatory for the aforementioned reviews. Although the direction and magnitude of effect size for gestational hypertension, pre-eclampsia and that of preterm birth are comparable with previous reviews,2,14 we have conducted few additional analyses in this review. These include effect of calcium supplementation during pregnancy on birthweight; admission to neonatal intensive care unit; induction of labour; preterm premature rupture of membrane; incidence of urolithiasis and renal colic. Figure 6 shows the forest plot for the effect of calcium supplementation on birthweight. The pooled results showed an extra gain of 85 g in the intervention group compared with control (mean difference 85 g [95% CI 37, 133]). The effect was more prominent in women with low calcium intake compared with those with adequate calcium intake. These findings of increased birthweight in the calcium group compared with control are consistent with findings of decrease in gestational hypertensive disorders. It has been shown previously that pre-eclamptic women have 2.7 times increased risk of having babies with intrauterine growth restriction.47 If calcium reduces incidence of gestational hypertensive disorders, it should also decrease intrauterine growth restriction which in turn would increase mean birthweight.

Side effects of calcium supplementation during pregnancy have not been well reported in the randomised studies. The most feared complication of increase calcium intake is development of calcium renal stones. Two large studies33,44 reported data on incidence of urolithiasis and renal colic and the pooled results showed a non-significant increased risk in the intervention group compared with control (RR 1.52 [95% CI 0.06, 40.67] and RR 1.75 [95% CI 0.51, 5.99], respectively] (Table 2). This shows that there is no increased risk of calcium stones in the intervention group compared with control.

The dose of calcium supplementation ranged from 500 mg/day to 2 g/day (Table 1). There were four studies32,35,44,46 that used a cumulative dose of <2 g/day. A subgroup analysis for incidence of pre-eclampsia according to dosage (<2 g/day vs. 2g/day) showed that effect is more pronounced and statistically significant in studies that used a dose of 2 g/day (RR 0.39 [95% CI 0.23, 0.67]) compared with those that used a dose <2 g/day (RR 0.56 [95 CI 0.30, 1.03]) (data not shown). This indicates that the most effective dose for calcium supplementation during pregnancy is 2 g/day. In most of the studies this amount of calcium was given in divided doses, usually in the form of two 500 mg tablets given twice daily.

Table 3 presents the results of subgroup analysis for developing countries vs. developed countries. It can be noted that effect of calcium supplementation during pregnancy was more marked and statistically significant for developing countries vs. developed countries. This observation is in accordance with the finding of the previous reviews that suggested that effect of calcium supplementation may only be relevant for populations with low baseline calcium intake,2,12,14 which is the most likely case for developing countries. It can thus be inferred that calcium supplementation during pregnancy should largely be recommended for developing countries or populations at risk of low dietary calcium intake.

The studies included in this review were in general of good methodological quality. Methods of sequence generation and allocation concealment were adequate in most of the studies (Table S1). The sample size ranged from 56 participants in study by Lopez-Jaramillo et al. 199040 to 8325 in study by Villar et al. 2006.44 A funnel plot drawn for risk of pre-eclampsia was asymmetric (data not shown). Studies with low standard error (SE) contributed the most to the pooled effect size; however, two studies with high SE had the highest protective effect. Publication bias may be one of the reasons of this asymmetry of the funnel plot; however, this may also be due to smaller sample size of some of the included studies.

Results of this review and that of previous reviews prove the efficacy of calcium supplementation in reducing gestational hypertensive disorders in populations with low calcium intake. Future research should focus on delivery platforms, regimens and programmatic aspect of the intervention. This should include consideration of dietary intake of calcium in particular populations and availability of fortified foods. For example, it would be relevant to assess the bioavailability of calcium when delivered via dietary modification or food fortification.48 It would be relevant to determine effectiveness of calcium supplementation by dietary modification/diversification populations based on access to dairy products compared with largely vegetarian sources. It is also important to calculate an internationally accepted value to define adequacy given the large variations in calcium recommendations in different countries of the world. Other issues of programmatic relevance include consideration of vehicles for fortification and cost-effectiveness of other forms of calcium supplementation.

Conflicts of interests

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Comments
  6. Conflicts of interests
  7. References
  8. Appendix
  9. Supporting Information

All the authors declare that they do not have a conflict of interest.

References

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Comments
  6. Conflicts of interests
  7. References
  8. Appendix
  9. Supporting Information
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Appendix

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Comments
  6. Conflicts of interests
  7. References
  8. Appendix
  9. Supporting Information

Appendix 1

  • 1.
    PubMed:
    Search strategy used: (Date of search September 15 2010)
    (Calcium OR ‘Calcium’[Mesh] OR ‘Calcium, Dietary’[Majr] and (‘Hypertension, Pregnancy-Induced’[Mesh] OR ‘Pre-Eclampsia’[Mesh] OR ‘Pregnancy, High-Risk’[Mesh]) OR ‘Pregnancy Complications’[Mesh]): Limits Human and Randomised controlled trial
  • 2.
    Cochrane library:
    Search strategy used: (Date of search October 7, 2010)
    #1 pregnancy, #2 Calcium, #3 (#1 AND #2), #4Hypertension, #5 Preeclampsia, #6Eclampsia, #7 Blood pressure, #8(#4 OR #5 OR #6 OR #7) (#3 AND #8)
  • 3.
    WHOLIS:
    Search Strategy Used: (Date of search October 7, 2010)
    (‘Calcium’ AND ‘pregnancy’) AND (‘Hypertension’ OR ‘pre-eclampsia’ OR ‘blood pressure’ OR ‘neonatal death’ OR ‘preterm ‘OR ‘low birth weight’)
  • 4.
    PAHO:
    Search term used: (Date of search October 7, 2010)
    ‘Calcium’ and ‘Pregnancy’

Supporting Information

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Comments
  6. Conflicts of interests
  7. References
  8. Appendix
  9. Supporting Information

Table S1. Risk of bias table for included studies according to latest Cochrane handbook.

FilenameFormatSizeDescription
PPE_1274_sm_TS1.doc76KSupporting info item

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