Background
High blood pressure with or without proteinuria are major causes of maternal death and morbidity worldwide (HMSO 1994; NHMRC 1993), and perinatal morbidity and mortality. Hypertension has been estimated to complicate 5% of all pregnancies and 11% of first pregnancies, half associated with pre-eclampsia, and accounting for up to 40,000 maternal deaths annually (Villar 2004). For this reason, strategies to reduce the risk of hypertensive disorders of pregnancy have received considerable attention (Bucher 1996; Carroli 1994; CLASP 1994; ECCPA 1996).
Preterm birth, a common association with hypertensive disorders, is the leading cause of early neonatal death and infant mortality, particularly in low-income countries (Villar 1994). Preterm survivors are at high risk of significant morbidity, especially respiratory disease and its sequelae, and long-term neurological morbidity (Johnson 1993). Interventions to reduce preterm birth have been reviewed by Villar et al (Villar 1998).
During early pregnancy, blood pressure normally falls, climbing slowly in later pregnancy to reach pre-pregnancy levels at term (Villar 1989). These normal changes in blood pressure make the diagnosis of hypertension during pregnancy difficult. Clinical methods of measuring blood pressure are also subject to considerable inaccuracy (Villar 2004). A widely accepted definition, however, is a diastolic blood pressure equal to or greater than 90 mmHg before the onset of labour, or an increase in systolic blood pressure of 30 mmHg or more, or in diastolic blood pressure of 15 mmHg or more. The consequences of high blood pressure are more serious if there is associated proteinuria. Hypertension and significant proteinuria (2+ by dipstick testing, equal to or greater than 300 mg per 24 hours, or equal to or greater than 500 mg per litre) usually indicate the presence of pre-eclampsia. Recently, the urine protein to creatinine ratio has been used increasingly as a measure of proteinuria (Yamasmit 2004). Predictors of poor outcome include low gestational age and high levels of proteinuria (von Dadelszen 2004).
An inverse relationship between calcium intake and hypertensive disorders of pregnancy was first described in 1980 (Belizan 1980). This was based on the observation that Mayan Indians in Guatemala, who traditionally soak their corn in lime before cooking, had a high calcium intake and a low incidence of pre-eclampsia and eclampsia. A very low prevalence of pre-eclampsia had been reported from Ethiopia where the diet, among other features, contained high levels of calcium (Hamlin 1962). These observations were supported by other epidemiological and clinical studies (Belizan 1988; Hamlin 1952; Repke 1991; Villar 1983; Villar 1987; Villar 1993), and led to the hypothesis that an increase in calcium intake during pregnancy might reduce the incidence of high blood pressure and pre-eclampsia among women with low calcium intake. An association has been found between pre-eclampsia and hypocalciuria (Segovia 2004); lower urine calcium to creatinine ratio (Kazerooni 2003); hypocalcaemia (Kumru 2003); lower plasma and higher membranous calcium (Kisters 2000); lower dietary milk intake (Duvekot 2002); and between eclampsia and hypocalcaemia (Isezuo 2004).
Low calcium intake may cause high blood pressure by stimulating either parathyroid hormone or renin release, thereby increasing intracellular calcium in vascular smooth muscle (Belizan 1988) and leading to vasoconstriction. A possible mode of action for calcium supplementation is that it reduces parathyroid release and intracellular calcium, and so reduces smooth muscle contractility. By a similar mechanism, calcium supplementation could also reduce uterine smooth muscle contractility and prevent preterm labour and delivery (Villar 1990). Calcium might also have an indirect effect on smooth muscle function by increasing magnesium levels (Repke 1989).
Calcium supplementation is attractive as a potential intervention to reduce the risk of a woman developing pre-eclampsia. Furthermore, the possibility of a protective effect on the risk of hypertension during childhood makes this even more important (Belizan 1997). It is relatively cheap and readily available. Also, it is likely to be safe for the woman and her child, although this safety would need to be clearly demonstrated in pregnant women before any attempt at widespread introduction into clinical practice. A theoretical risk of increased renal tract stone formation has not been substantiated, and no other adverse effects of calcium supplementation have been documented.
This hypothesis was tested in several randomised trials commencing in the late 1980s which suggested a promising beneficial effect for calcium supplementation. The first systematic reviews highlighted the need for larger trials to assess the effects on important clinical outcomes in addition to pre-eclampsia and preterm delivery, such as perinatal mortality (Carroli 1994; Duley 1995). A subsequent systematic review (Bucher 1996) came to more enthusiastic conclusions, but this optimism was not confirmed by a large trial in the USA (CPEP 1997). These discrepancies have elicited discussion in the literature (Villar 2000). More recently, a large trial in communities with low dietary calcium intake has been reported (WHO 2006).
There is thus a need for an updated systematic review of the current evidence concerning the effectiveness of calcium supplementation in pregnancy.
Objectives
To determine, from the best available evidence, the effect of calcium supplementation during pregnancy on the risk of high blood pressure and related maternal and fetal or neonatal adverse outcomes. Subgroup analyses tested whether these effects were influenced by whether:
- women were at low or average risk of hypertensive disorders, or at high risk;
- women had low or adequate dietary calcium intake prior to trial entry.
Methods
Criteria for considering studies for this review
Types of studies
All published, unpublished and ongoing trials with random allocation to calcium supplementation during pregnancy versus placebo (see 'Methods of the review'). Quasi-random designs were excluded.
Types of participants
Pregnant women, regardless of the risk of hypertensive disorders of pregnancy. Women with diagnosed hypertensive disorders of pregnancy were excluded.
Prespecified subgroups to be compared.
- Women at low or average risk of hypertensive disorders of pregnancy (unselected).
- Women at above average risk of hypertensive disorders of pregnancy. These included women selected by the trial authors on the basis of an increased risk of hypertensive disorders of pregnancy (eg teenagers, women with previous pre-eclampsia, women with increased sensitivity to angiotensin II, women with pre-existing hypertension). Primiparity alone was not regarded as a high risk factor.
- Women or populations with low baseline dietary calcium intake (as defined by trial authors, or if not defined, mean intake less than 900 mg per day).
- Women or populations with adequate dietary calcium intake (as defined by trial authors, or if not defined, mean intake equal to or greater than 900 mg per day).
Types of interventions
Supplementation with calcium from at the latest 34 weeks of pregnancy; compared with placebo treatment. We excluded studies with no placebo.
We limited the initial analysis to intended supplementation with at least one gram of calcium per day. Future updates of this review will include an analysis of effect by dosage, including lower dosage regimens.
Types of outcome measures
In the original protocol we prespecified 15 clinical measures of maternal and fetal or neonatal morbidity and mortality. In October 2004 we added seven additional outcomes (marked * below):
For the women
(1) High blood pressure as defined by trial authors, with or without proteinuria. Ideally, high blood pressure would be defined as diastolic blood pressure equal to or greater than 90 mmHg, or an increase in systolic blood pressure of 30 mmHg or more, or in diastolic blood pressure of 15 mmHg or more.
(2) High blood pressure with significant proteinuria, as defined by trial authors. Ideally, proteinuria would be defined as 2+ by dipstick testing, equal to or greater than 300 mg per 24 hours, or equal to or greater than 500 mg per litre. Although the strict definition of pre-eclampsia includes confirmation of no hypertension or proteinuria outside pregnancy, for convenience the above definition will be referred to in this review as pre-eclampsia.
(3) Maternal death or serious morbidity. Serious morbidity includes eclampsia; renal failure; syndrome of haemolysis, elevated liver enzymes and low platelets (HELLP syndrome); and admission to intensive care. This will be a composite outcome of death or at least one measure of serious morbidity. In addition each individual outcome will be presented.
(4) Placental abruption.
(5) Caesarean section.
(6) *Proteinuria.
(7) *Severe pre-eclampsia as defined by trial authors.
(8) *Eclampsia.
(9) *HELLP syndrome.
(10) *Intensive care unit admission.
(11) *Maternal death.
(12) Mother's hospital stay seven days or more.
For the child
(13) Preterm birth (birth before 37 weeks of estimated gestation).
(14) Low birthweight (the first weight obtained after birth less than 2500 g).
(15) Neonate small-for-gestational age as defined by trial authors.
(16) Admission to neonatal intensive care unit (ICU).
(17) Neonate in intensive care unit seven days or more.
(18) Stillbirth or death before discharge from hospital.
(19) *Death or severe neonatal morbidity.
Long-term outcomes
(20) Childhood disability.
(21) Systolic blood pressure greater than 95th percentile during childhood.
(22) Diastolic blood pressure greater than 95th percentile during childhood.
The primary outcomes are high blood pressure, pre-eclampsia, preterm birth, admission to neonatal intensive care unit, and stillbirth of neonatal death. Subgroup analyses are limited to the primary outcomes.
Only those outcomes with data appear in the analysis table.
Search methods for identification of studies
Electronic searches
We searched the Cochrane Pregnancy and Childbirth Group Trials Register by contacting the Trials Search Co-ordinator (February 2006). We updated this search on 31 October 2009 and added the results to Studies awaiting classification.
The Cochrane Pregnancy and Childbirth Group’s Trials Register is maintained by the Trials Search Co-ordinator and contains trials identified from:
- quarterly searches of the Cochrane Central Register of Controlled Trials (CENTRAL);
- weekly searches of MEDLINE;
- handsearches of 30 journals and the proceedings of major conferences;
- weekly current awareness alerts for a further 44 journals plus monthly BioMed Central email alerts.
Details of the search strategies for CENTRAL and MEDLINE, the list of handsearched journals and conference proceedings, and the list of journals reviewed via the current awareness service can be found in the ‘Specialized Register’ section within the editorial information about the Cochrane Pregnancy and Childbirth Group.
Trials identified through the searching activities described above are each assigned to a review topic (or topics). The Trials Search Co-ordinator searches the register for each review using the topic list rather than keywords.
In addition, we searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2005, Issue 4) using the terms calcium AND pregnan* AND (hypertens* or blood press*).
We included additional information obtained from the trialists in the previous version of this review (Duley 1995) for five studies (Belizan 1991; L-Jaramillo 1989; Marya 1987; Villar 1987; Villar 1990).
We did not apply any language restrictions.
Data collection and analysis
Two review authors independently assessed the methodological quality and other inclusion criteria of the identified trials. At least one of these authors had no involvement in the trial. We resolved disagreements by consensus. The primary assessment for inclusion was based on concealment of allocation and whether the trial was placebo controlled.
Two authors independently extracted and cross-checked the data. Descriptive data included authors, year of publication, country, time span of the trial, maternal age, parity, type of placebo, baseline dietary calcium intake, type, dose, onset and duration of calcium supplementation, compliance, co-interventions, trial quality assessments, and number randomised and analysed.
We compared categorical data using relative risks and their 95% confidence intervals. We tested for statistical heterogeneity between trials using the I-squared statistic, with values greater than 50% indicating significant heterogeneity. In the absence of significant heterogeneity, data were pooled using a fixed-effect model. If there was significant heterogeneity, a random-effects model was used and an attempt made to identify potential sources of heterogeneity (Greenland 1994; Villar 1995) based on subgroup analyses by risk of hypertensive disorders, baseline dietary calcium intake, trial quality and trial size.
For continuous data, we calculated pooled estimates of effect size from a weighted average, with weight based on the inverse of the variance (Early Breast Ca 1990). We identified comparisons, outcomes and subgroups other than those prespecified in the original protocol as 'post hoc' analyses.
Results
Description of studies
See: Characteristics of included studies; Characteristics of excluded studies; Characteristics of ongoing studies.
We included twelve studies. Four were multicentre studies, one in Argentina (Belizan 1991), one in the USA (CPEP 1997), another in Australia (Crowther 1999) and the fourth was international (WHO 2006). Most of the 15,206 women recruited to these studies were low risk (14,619 women) and had a low dietary intake of calcium (10,154). Most studies only recruited women who were nulliparous or primiparous. One study did not state the parity of women recruited (Niromanesh 2001) and another commented that most women were nulliparous (Villar 1990). For most studies the intervention was 1.5 g to 2 g per day of calcium.
One included study has conducted long-term follow up of the children whose mothers were recruited to these trials (Belizan 1991). In this study, only the subset of women recruited in private clinics were contacted.
One other study has reported outcome for a small subset of women (CPEP 1997), but these data did not meet the inclusion criteria for this review.
Twenty-three studies were excluded from the review. (Fourteen reports from an updated search in October 2009 have been added to Studies awaiting classification.)
Risk of bias in included studies
See table of 'Characteristics of included studies'. All were well designed, double-blind, placebo-controlled trials. Prespecified outcome data were not available from all trials. The possibility of reporting bias must be kept in mind for those outcomes with unreported data from some trials.
In Lopez-Jaramillo (L-Jaramillo 1990), a large discrepancy in numbers allocated to each group is not accounted for.
In some trials, individual denominators were not given for specific outcomes. Where it was clear that the outcomes were not measured in the entire group, we have adjusted the denominators accordingly.
In other respects, the methodology of the studies included appears sound.
Effects of interventions
We included twelve studies. Significant heterogeneity of results occurred for four outcomes: pre-eclampsia; high blood pressure; preterm birth and birthweight less than 2500 g. Factors accounting for the heterogeneity appeared to be maternal risk at trial entry and dietary calcium. The small trials have more extreme results than large trials, but as all the small trials recruited high-risk women this could also be related to risk status. In view of the heterogeneity, we used a random-effects model for these four outcomes.
(1) High blood pressure with or without proteinuria
The results follow a similar pattern to those for pre-eclampsia (see below). Overall there was less high blood pressure with calcium supplementation rather than placebo (11 trials, 14,946 women: relative risk (RR) random-effects model 0.70, 95% confidence interval (CI) 0.57 to 0.86). The reduction in relative risk was greatest for the small trials (fewer than 400 women: 7 trials, 675 women, RR 0.38, 95% CI 0.21 to 0.68), for women at high risk of developing pre-eclampsia (4 trials, 327 women: RR 0.47, 95% CI 0.22 to 0.97), and for those with low baseline dietary calcium (6 trials, 9894 women: RR 0.47, 95% CI 0.29 to 0.76).
(2) Pre-eclampsia
Overall, there was a reduction in the risk of pre-eclampsia (12 trials, 15,206 women: RR 0.48, 95% CI 0.33 to 0.69). This reduction in relative risk was greatest for women at high risk of pre-eclampsia (5 trials, 587 women: RR 0.22, 95% CI 0.12 to 0.42), and for those with low baseline calcium intake (7 trials, 10,154 women: RR 0.36, 95% CI 0.18 to 0.70).
When subgrouped by both dietary calcium intake and study size, the effect size appeared to be associated most strongly with study size (in the small studies, relative risks 0.21 for the low calcium trials and 0.26 for the adequate calcium trials, and in the large studies 0.87 and 0.70 respectively).
(3) Maternal death or serious morbidity
The relative risk of having the composite outcome maternal death or serious morbidity was reduced for women allocated calcium supplementation compared with placebo (4 trials, 9732 women: RR 0.80, 95% CI 0.65 to 0.97).
(4) Placental abruption
In the five trials reporting this outcome, there was no clear difference between the groups (14,309 women: RR 0.86 95% CI 0.55 to 1.34).
(5) Caesarean section
There was no statistically significant effect on the relative risk of caesarean section (7 trials, 14,710 women: RR 0.95, 95% CI 0.88 to 1.01).
6) *Proteinuria
Proteinuria was reported in only one trial (WHO 2006), and there was no overall difference between the groups (8312 women: RR 1.04, 95% CI 0.86 to 1.26).
(7) *Severe pre-eclampsia as defined by trial authors
Severe pre-eclampsia was reported in only one trial (WHO 2006). Again, there was no clear difference between the groups (1 trial, 8302 women: RR 0.74, 95% CI 0.48 to 1.15).
(8) *Eclampsia
Eclampsia was reported by the two largest trials (CPEP 1997; WHO 2006). There was no clear difference between the groups (2 trials, 12,901 women: RR 0.73, 95% CI 0.41 to 1.27).
(9) *HELLP syndrome
HELLP syndrome was also reported only by the two largest studies (CPEP 1997; WHO 2006). The relative risk was higher for women allocated calcium supplementation, rather than placebo (2 trials, 12,901 women: RR 2.67, 95% CI 1.05 to 6.82).
(10) *Maternal intensive care unit admission
Admission to intensive care was reported only by one trial (WHO 2006). There was no clear difference between the groups (1 trial, 8312 women: RR 0.84, 95% CI 0.66 to 1.07).
(11) *Maternal death
Maternal deaths were reported only by one trial (WHO 2006). One death occurred in the calcium group and six in the placebo group, a difference which was not statistically significant (RR 0.17, 95% CI 0.02 to 1.39).
(12) Mother's hospital stay seven days or more
Data were not available for this outcome.
(13) Preterm birth
There was no overall effect on preterm birth (10 trials 14,751 women; RR 0.81, 95% CI 0.64 to 1.03). However, the relative risk of preterm birth was reduced amongst women at high risk of developing pre-eclampsia recruited to four small trials (568 women: RR 0.45, 95% CI 0.24 to 0.83).
(14) Birthweight less than 2500 g
There was no overall effect on the risk of having a baby with birthweight less than 2500 g (8 trials, 14,359 women: RR 0.84, 95% CI 0.68 to 1.03).
(15) Neonate small-for-gestational age
There was no overall effect on the relative risk of the baby being born small-for-gestational age (3 trials 13,091 women: RR 1.10, 95% CI 0.88 to 1.37).
(16) Admission to neonatal intensive care unit
There was no overall effect on the relative risk of admission to a neonatal intensive care unit (4 trials 13,406 women: RR 1.05, 95% CI 0.94 to 1.18).
(17) Neonate in intensive care unit seven days or more
Data were not available for this outcome.
(18) Stillbirth or death before discharge from hospital
There was no overall effect on the relative risk of a stillbirth or the baby dying before discharge from hospital (10 trials, 15,141 women: RR 0.89 95% CI 0.73 to 1.09).
(19) *Death or severe neonatal morbidity
No data were available for this outcome.
(20) Childhood disability
Data were not available for this outcome.
(21) Childhood systolic blood pressure greater than 95th percentile
One trial has assessed during childhood a subset of the children recruited whilst in utero (Belizan 1991). At about seven years of age diastolic blood pressure greater than 95th percentile was reduced (1 trial, 514 women: RR 0.59, 95% CI 0.39 to 0.91). While the baseline calcium intake in the original study was low (calcium group mean 646 mg, standard deviation (SD) 396, placebo group 642, SD 448 in a sample assessed during the first four months of the study), the group followed up were only from among the 614 women from the private hospital, not the 580 from the public hospitals. Their dietary calcium intake may have differed from the mean (more likely to be higher in more affluent women). The baseline calcium status of the women in this part of the study therefore cannot be classified.
A limited follow up of mothers and infants from the CPEP 1997 study found reduced systolic blood pressure at two years of age in the calcium supplementation group (mean 95.4 mmHg, SD 7.6, n = 35 versus 100.2, 7.9, n = 18). The data have not been included in this review because the low and unequal follow-up rate (35 and 18 from 497 invited to participate) limit the reliability of the results. In another report of (CPEP 1997), Hatton 2003 reduced systolic blood pressure was found in the offspring of the calcium supplementation group at two years of age. These data have also not been included because of the high losses to follow up.
(22) Childhood diastolic blood pressure greater than 95th percentile
Data were available only from the Belizan 1991 study. The difference was not statistically significant.
Discussion
Calcium supplementation with at least one gram of calcium is associated with a halving in the relative risk of pre-eclampsia, with the confidence intervals putting the true effect anywhere between a 31% reduction and a 67% reduction. Women with an adequate dietary intake of calcium were the only subgroup for which this was not statistically significant, nevertheless the point estimate for this subgroup of women was a 38% reduction. The greatest reduction in risk was for women at high risk and those with low baseline dietary calcium intake. There was also a 30% reduction in the risk of gestational hypertension, with again the greatest effect being amongst women at high risk and those with a low calcium intake at trial entry. There was no overall effect on the relative risk of preterm birth, although a moderate reduction associated with calcium supplementation remains possible. There was a halving in the relative risk of preterm birth for women at high risk of pre-eclampsia. This result should be interpreted with caution, as the numbers of women in the subgroup are small and the result may therefore reflect the play of chance.
Although pre-eclampsia was reduced, this was not clearly reflected in any reduction in severe pre-eclampsia, eclampsia, or admission to intensive care. Nevertheless, the point estimates for these outcomes favoured calcium supplementation, and so moderate reductions in these outcomes remain possible. Also, the relative risk of the composite outcome 'maternal death or severe morbidity' was reduced by 20% (95% CI 35% to 3%) for women allocated calcium supplementation. In the two trials reporting HELLP syndrome, the relative risk of this outcome seemed to be increased in association with calcium supplementation.
No side-effects of calcium supplementation have been recorded in the trials reviewed. There is little information about the long-term follow up of children within these trials, with the exception of a reduction in childhood systolic hypertension in the one study to measure this outcome. There is no information about any possible changes in the use of healthcare resources associated with calcium supplementation. It would seem plausible that a reduction in gestational hypertension and pre-eclampsia might lead to fewer antenatal visits, less admission for antenatal care and fewer inductions of labour. However, these trials do not provide data on these outcomes.
Heterogeneity in the results seems to be largely associated with study size, with the small studies having the most positive results. As the small studies tended to recruit high risk women, at least some of the heterogeneity may be explained by calcium having a greater, effect for high-risk women. An alternative explanation may be that there is publication bias, with small studies that failed to report an effect for calcium supplementation not being published. The data on heterogeneity related to sample size should be interpreted with caution, as the sensitivity analysis was post-hoc, and the cut-off point for sample size (400) was arbitrary.
There are no clear differences in any other outcomes, although for several outcomes the confidence intervals are approaching statistical significance. So, for caesarean section, a small (5%) reduction in relative risk associated with calcium supplementation is possible. For preterm birth, the point estimate is for a 19% reduction in risk, and for stillbirth and death before discharge from hospital 11%, although for both these outcomes no effect or a small increase in risk has not been excluded.
Taken together, these trials show a halving in the relative risk of pre-eclampsia. This is reflected in more modest reductions in the relative risk of gestational hypertension and of maternal death or serious morbidity. There are no clear effects on other substantive outcomes at discharge from hospital
These modest results contrast with the large epidemiological differences between populations with adequate and low dietary calcium intake (Belizan 1980; Hamlin 1952; Hamlin 1962). Possible explanations include the following:
(1) Dietary calcium may be a marker for other aetiological factors.
(2) Starting supplementation in the middle trimester of pregnancy may be too late to be fully effective.
The finding of reduced childhood hypertension needs replication, but if true has far-reaching implications for public health. Although based on only a partial follow up in one study, this finding is supported by a very limited follow up in two studies (CPEP 1997), as well as observational (McGarvey 1991) and animal (Bergel 2002) studies.
Authors' conclusions
Implications for practice The reduction in pre-eclampsia, and in maternal death or severe morbidity, support the use of calcium supplementation, particularly for those with low dietary intake. |
Implications for research Any future trials should collect information about the use of health service resources, as well as other clinical outcomes. The minimum dose in this review was one gram of calcium daily. It would now be relevant to assess whether supplementation via dietary modification, for women with low calcium intake, has the same benefits as the tablets administered in these trials. Further research is also needed provide reassurance that calcium supplementation during pregnancy does not have any adverse effects for the children exposed whilst in utero, and to verify the whether it reduces childhood hypertension. Research into the effects of calcium supplementation combined with low-dose aspirin would be of interest. [Note: The 15 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.] |
Acknowledgements
We thank the trial authors who have contributed additional data for this review, and Jose Villar for constructive criticism of the protocol.
Data and analyses
- Top of page
- Background
- Objectives
- Methods
- Results
- Discussion
- Authors' conclusions
- Acknowledgements
- Data and analyses
- What's new
- History
- Contributions of authors
- Declarations of interest
- Sources of support
- Index terms
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
What's new
Last assessed as up-to-date: 1 March 2006.
| |||||||||
History
Protocol first published: Issue 2, 1998
Review first published: Issue 3, 1998
| |||||||||||||||||||||
Contributions of authors
Lelia Duley prepared the original review in the Oxford Database of Perinatal Trials.
Alvaro Atallah and Justus Hofmeyr prepared the protocol for the current Cochrane review.
Justus Hofmeyr prepared the data analysis and is primarily responsible for maintaining the review, with input from Lelia Duley and Alvaro Atallah.
Declarations of interest
Justus Hofmeyr is a collaborator in the WHO Calcium Trial (WHO 2006), which was included in this review.
Sources of support
Internal sources
- Universidade Federal de Sao Paulo/Escola Paulista de Medicina, Brazil.
- Medical Research Council, UK.
- Department for International Development, UK.
- (GJH) Effective Care Research Unit, University of the Witwatersrand/Fort Hare, Eastern Cape Department of Health, South Africa.
External sources
- UNDP/UNFPA/WHO/World Bank (HRP), Switzerland.
Index terms
Medical Subject Headings (MeSH)
*Dietary Supplements; Calcium, Dietary [*administration & dosage]; Hypertension [*prevention & control]; Pre-Eclampsia [*prevention & control]; Pregnancy Complications, Cardiovascular [*prevention & control]; Randomized Controlled Trials as Topic
MeSH check words
Female; Humans; Pregnancy
* Indicates the major publication for the study