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Calcium supplementation commencing before or early in pregnancy, for preventing hypertensive disorders of pregnancy.

The Cochrane database of systematic reviews
January 1, 1970
G Justus Hofmeyr et al. (4 authors)
Journal ArticleResearch Support, Non-U.S. Gov'tSystematic ReviewHuman Study
Study Details

Study Goal

The researchers aimed to determine whether calcium supplementation before or early in pregnancy reduces the risk of pre-eclampsia and other hypertensive disorders, maternal morbidity and mortality, and adverse fetal and neonatal outcomes.

Results Summary

The study found that calcium supplementation may slightly reduce the risk of the composite outcome of pre-eclampsia or pregnancy loss, but results were inconclusive for most other outcomes. No significant differences were observed in severe maternal morbidity, pregnancy loss, or neonatal outcomes.

Population

Non-pregnant women with previous pre-eclampsia from Argentina, South Africa, and Zimbabwe.

Effective Dosage

500 mg daily before conception until 20 weeks' gestation, then 1.5 g daily until birth.

Duration

From pre-conception until birth.

Interactions

None mentioned

Extracted Claims (13)
InterventionDirectionEndpointPopulationDosageImpactClaim #
calcium supplementation in the second half of pregnancy
decrease
the serious consequences of pre-eclampsia
-
-
reduces
#1
calcium supplementation in the second half of pregnancy
no change
the overall risk of pre-eclampsia
-
-
has limited effect on
#2
calcium supplementation commencing before conception
no change
the risk of pre-eclampsia
non-pregnant women with previous pre-eclampsia
RR 0.80, 95% CI 0.61 to 1.06
may make little or no difference to
#3
calcium supplementation
decrease
pre-eclampsia or pregnancy loss or stillbirth (or both) at any gestational age
non-pregnant women with previous pre-eclampsia
RR 0.82, 95% CI 0.66 to 1.00
may slightly reduce the risk of
#4
calcium supplementation
no change
the severe maternal morbidity and mortality index
non-pregnant women with previous pre-eclampsia
RR 0.93, 95% CI 0.68 to 1.26
may make little or no difference to
#5
calcium supplementation
no change
pregnancy loss or stillbirth at any gestational age
non-pregnant women with previous pre-eclampsia
RR 0.83, 95% CI 0.61 to 1.14
may make little or no difference to
#6
calcium supplementation
no change
caesarean section
non-pregnant women with previous pre-eclampsia
RR 1.11, 95% CI 0.96 to 1.28
may make little or no difference to
#7
calcium supplementation
no change
birthweight < 2500 g
non-pregnant women with previous pre-eclampsia
RR 1.00, 95% CI 0.76 to 1.30
may make little or no difference to
#8
calcium supplementation
no change
preterm birth < 37 weeks
non-pregnant women with previous pre-eclampsia
RR 0.90, 95% CI 0.74 to 1.10
may make little or no difference to
#9
calcium supplementation
no change
early preterm birth < 32 weeks
non-pregnant women with previous pre-eclampsia
RR 0.79, 95% CI 0.56 to 1.12
may make little or no difference to
#10
calcium supplementation
no change
pregnancy loss, stillbirth or neonatal death before discharge
non-pregnant women with previous pre-eclampsia
RR 0.82, 95% CI 0.61 to 1.10
may make little or no difference to
#11
calcium supplementation
no change
perinatal death, or neonatal intensive care unit admission for > 24h, or both
non-pregnant women with previous pre-eclampsia
RR 1.11, 95% CI 0.77 to 1.60
may make little or no difference to
#12
calcium supplementation
decrease
women experiencing the composite outcome pre-eclampsia or pregnancy loss at any gestational age
non-pregnant women with previous pre-eclampsia
-
may reduce the risk of
#13
Abstract

BACKGROUND: The hypertensive disorders of pregnancy include pre-eclampsia, gestational hypertension, chronic hypertension, and undefined hypertension. Pre-eclampsia is considerably more prevalent in low-income than in high-income countries. One possible explanation for this discrepancy is dietary differences, particularly calcium deficiency. Calcium supplementation in the second half of pregnancy reduces the serious consequences of pre-eclampsia, but has limited effect on the overall risk of pre-eclampsia. It is important to establish whether calcium supplementation before, and in early pregnancy (before 20 weeks' gestation) has added benefit. Such evidence could count towards justification of population-level interventions to improve dietary calcium intake, including fortification of staple foods with calcium, especially in contexts where dietary calcium intake is known to be inadequate. This is an update of a review first published in 2017. OBJECTIVES: To determine the effect of calcium supplementation, given before or early in pregnancy and for at least the first half of pregnancy, on pre-eclampsia and other hypertensive disorders, maternal morbidity and mortality, and fetal and neonatal outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Trials Register (31 July 2018), PubMed (13 July 2018), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP; 31 July 2018), and reference lists of retrieved studies. SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCT) of calcium supplementation, including women not yet pregnant, or women in early pregnancy. Cluster-RCTs, quasi-RCTs, and trials published as abstracts were eligible, but we did not identify any. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy. They assessed the quality of the evidence for key outcomes using the GRADE approach. MAIN RESULTS: Calcium versus placeboWe included one study (1355 women), which took place across multiple hospital sites in Argentina, South Africa, and Zimbabwe. Most analyses were conducted only on 633 women from this group who were known to have conceived, or on 579 who reached 20 weeks' gestation; the trial was at moderate risk of bias due to high attrition rates pre-conception. Non-pregnant women with previous pre-eclampsia received either calcium 500 mg daily or placebo, from enrolment until 20 weeks' gestation. All participants received calcium 1.5 g daily from 20 weeks until birth.Primary outcomes: calcium supplementation commencing before conception may make little or no difference to the risk of pre-eclampsia (69/296 versus 82/283, risk ratio (RR) 0.80, 95% confidence interval (CI) 0.61 to 1.06; low-quality evidence). For pre-eclampsia or pregnancy loss or stillbirth (or both) at any gestational age, calcium may slightly reduce the risk of this composite outcome, however the 95% CI met the line of no effect (RR 0.82, 95% CI 0.66 to 1.00; low-quality evidence). Supplementation may make little or no difference to the severe maternal morbidity and mortality index (RR 0.93, 95% CI 0.68 to 1.26; low-quality evidence), pregnancy loss or stillbirth at any gestational age (RR 0.83, 95% CI 0.61 to 1,14; low-quality evidence), or caesarean section (RR 1.11, 95% CI 0.96 to 1,28; low-quality evidence).Calcium supplementation may make little or no difference to the following secondary outcomes: birthweight < 2500 g (RR 1.00, 95% CI 0.76 to 1.30; low-quality evidence), preterm birth < 37 weeks (RR 0.90, 95% CI 0.74 to 1.10), early preterm birth < 32 weeks (RR 0.79, 95% CI 0.56 to 1.12), and pregnancy loss, stillbirth or neonatal death before discharge (RR 0.82, 95% CI 0.61 to 1.10; low-quality evidence), no conception, gestational hypertension, gestational proteinuria, severe gestational hypertension, severe pre-eclampsia, severe pre-eclamptic complications index. There was no clear evidence on whether or not calcium might make a difference to perinatal death, or neonatal intensive care unit admission for > 24h, or both (RR 1.11, 95% CI 0.77 to 1.60; low-quality evidence).It is unclear what impact calcium supplementation has on Apgar score < 7 at five minutes (RR 0.43, 95% CI 0.15 to 1.21; very low-quality evidence), stillbirth, early onset pre-eclampsia, eclampsia, placental abruption, intensive care unit admission > 24 hours, maternal death, hospital stay > 7 days from birth, and pregnancy loss before 20 weeks' gestation. AUTHORS' CONCLUSIONS: The single included study suggested that calcium supplementation before and early in pregnancy may reduce the risk of women experiencing the composite outcome pre-eclampsia or pregnancy loss at any gestational age, but the results are inconclusive for all other outcomes for women and babies. Therefore, current evidence neither supports nor refutes the routine use of calcium supplementation before conception and in early pregnancy.To determine the overall benefit of calcium supplementation commenced before or in early pregnancy, the effects found in the study of calcium supplementation limited to the first half of pregnancy need to be added to the known benefits of calcium supplementation in the second half of pregnancy.Further research is needed to confirm whether initiating calcium supplementation pre- or in early pregnancy is associated with a reduction in adverse pregnancy outcomes for mother and baby. Research could also address the acceptability of the intervention to women, which was not covered by this review update.

Medical Subject Headings (MeSH)
Calcium, DietaryDietary SupplementsFemaleHumansHypertensionPre-EclampsiaPregnancyPregnancy Complications, CardiovascularPremature BirthRandomized Controlled Trials as Topic
Study Links
Quality Scores
Safety85
Efficacy60/10
Quality75/10
Citation Metrics
Total Citations40
Citations/Year6.7
Relative Citation Ratio2.04
NIH Percentile75.1%
Research Impact Scores
APT Score0.95
Weight Score1.76
Normalized Score0.73
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