Panacea Index Logo

Command Palette

Search for a command to run...

Calcium supplementation commencing before or early in pregnancy, or food fortification with calcium, for preventing hypertensive disorders of pregnancy.

The Cochrane database of systematic reviews
January 1, 1970
G Justus Hofmeyr et al. (2 authors)
Journal ArticleResearch Support, Non-U.S. Gov'tReviewSystematic ReviewHuman Study
Study Details

Study Goal

The researchers aimed to determine whether calcium supplementation combined with N-Acetylcysteine and other antioxidants/supplements could reduce pre-eclampsia and adverse pregnancy outcomes.

Results Summary

The study found that calcium plus N-Acetylcysteine and other supplements may slightly reduce pre-eclampsia and early pregnancy loss, but results were uncertain due to wide confidence intervals and small sample size. A reduction in composite outcomes (pre-eclampsia and/or pregnancy loss) was observed, but the effects could not be attributed solely to N-Acetylcysteine.

Population

60 pregnant women with low antioxidant status in early pregnancy (8-12 weeks gestation) at an academic hospital in Indonesia.

Effective Dosage

200 mg N-Acetylcysteine (alongside 800 mg calcium and other supplements), taken twice daily.

Duration

From 8-12 weeks of gestation until delivery.

Interactions

None mentioned

Extracted Claims (7)
InterventionDirectionEndpointPopulationDosageImpactClaim #
calcium supplementation in the second half of pregnancy
decrease
the serious consequences of pre-eclampsia
women with low dietary calcium intake
-
reduces
#1
calcium supplementation in the second half of pregnancy
no change
the overall risk of pre-eclampsia
-
-
has limited effect
#2
calcium supplementation plus antioxidants and other supplements
decrease
pre-eclampsia (gestational hypertension and proteinuria)
women with low antioxidant levels
risk ratio (RR) 0.24, 95% confidence interval (CI) 0.06 to 1.01
may slightly reduce
#3
calcium plus antioxidants and other supplements
decrease
early pregnancy loss before 20 weeks' gestation
-
RR 0.06, 95% CI 0.00 to 1.04
may be slightly reduced
#4
calcium plus antioxidants and other supplements
no change
severe maternal morbidity and mortality index
-
RR 0.36, 95% CI 0.04 to 3.23
no clear difference
#5
calcium plus antioxidants and other supplements
decrease
the composite outcome pre-eclampsia and/or pregnancy loss at any gestational age
-
RR 0.13, 95% CI 0.03 to 0.50
observed a reduction
#6
calcium plus antioxidant/supplement
decrease
pregnancy loss/stillbirth at any gestational age
-
RR 0.06, 95% CI 0.00 to 0.92
observed a reduction
#7
Abstract

BACKGROUND: Pre-eclampsia is considerably more prevalent in low- than 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 and is recommended by the World Health Organization (WHO) for women with low dietary calcium intake, but has limited effect on the overall risk of pre-eclampsia. It is important to establish whether calcium supplementation before and in early pregnancy has added benefit. Such evidence would be justification for population-level fortification of staple foods with calcium. OBJECTIVES: To determine the effect of calcium supplementation or food fortification with calcium, commenced before or early in pregnancy and continued at least until mid-pregnancy, on pre-eclampsia and other hypertensive disorders, maternal morbidity and mortality, as well as fetal and neonatal outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Trials Register (10 August 2017), PubMed (29 June 2017), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (10 August 2017) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials of calcium supplementation or food fortification which include women of child bearing age not yet pregnant, or in early pregnancy. Cluster-RCTs, quasi-RCTs and trials published in abstract form only would have been eligible for inclusion in this review but none were identified. Cross-over designs are not appropriate for this intervention.The scope of this review is to consider interventions including calcium supplementation with or without additional supplements or treatments, compared with placebo or no intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: This review is based on one RCT (involving 60 women) which looked at calcium plus additional supplements versus control. The women (who had low antioxidant status) were in the early stages of pregnancy. We did not identify any studies where supplementation commenced pre-pregnancy. Another RCT comparing calcium versus placebo is ongoing but not yet complete. We did not identify any studies looking at any of our other planned comparisons. Calcium plus antioxidants and other supplements versus placeboWe included one small study (involving 60 women with low antioxidant levels) which was conducted in an academic hospital in Indondesia. The study was at low risk of bias for all domains with the exception of selective reporting, for which it was unclear. Women in the intervention group received calcium (800 mg) plus N-acetylcysteine (200 mg), Cu (2 mg), Zn (15 mg), Mn (0.5 mg) and selenium (100 mcg) and vitamins A (1000 IU), B6 (2.2 mg), B12 (2.2 mcg), C (200 mg), and E (400 IU) versus the placebo control group of women who received similar looking tablets containing iron and folic acid. Both groups received iron (30 mg) and folic acid (400 mcg). Tablets were taken twice daily from eight to 12 weeks of gestation and then throughout pregnancy.The included study found that calcium supplementation plus antioxidants and other supplements may slightly reduce pre-eclampsia (gestational hypertension and proteinuria) (risk ratio (RR) 0.24, 95% confidence interval (CI) 0.06 to 1.01; low-quality evidence), but this is uncertain due to wide confidence intervals just crossing the line of no effect, and small sample size. It appears that earlypregnancy loss before 20 weeks' gestation (RR 0.06, 95% CI 0.00 to 1.04; moderate-quality evidence) may be slightly reduced by calcium plus antioxidants and other supplements, but this outcome also has wide confidence intervals, which just cross the line of no effect. Very few events were reported under the composite outcome, severe maternal morbidity and mortality index and no clear difference was seen between groups (RR 0.36, 95% CI 0.04 to 3.23; low-quality evidence). However, the included study observed a reduction in the composite outcome pre-eclampsia and/or pregnancy loss at any gestational age (RR 0.13, 95% CI 0.03 to 0.50; moderate-quality evidence), and pregnancy loss/stillbirth at any gestational age (RR 0.06, 95% CI 0.00 to 0.92; moderate-quality evidence) in the calcium plus antioxidant/supplement group.Other outcomes reported (placental abruption, severe pre-eclampsia and preterm birth (less than 37 weeks' gestation)) were too infrequent for meaningful analysis. No data were reported for the outcomes caesarean section, birthweight < 2500 g, Apgar score less than seven at five minutes, death or admission to neonatal intensive care unit (ICU), or pregnancy loss, stillbirth or neonatal death before discharge from hospital. AUTHORS' CONCLUSIONS: The results of this review are based on one small study in which the calcium intervention group also received antioxidants and other supplements. Therefore, we are uncertain whether any of the effects observed in the study were due to calcium supplementation or not. The evidence in this review was graded low to moderate due to imprecision. There is insufficient evidence on the effectiveness or otherwise of pre- or early-pregnancy calcium supplementation, or food fortification for preventing hypertensive disorders of pregnancy.Further research is needed to determine whether pre- or early-pregnancy supplementation, or food fortification with calcium is associated with a reduction in adverse pregnancy outcomes such as pre-eclampsia and pregnancy loss. Such studies should be adequately powered, limited to calcium supplementation, placebo-controlled, and include relevant outcomes such as those chosen for this review.There is one ongoing study of calcium supplementation alone versus placebo and this may provide additional evidence in future updates.

Medical Subject Headings (MeSH)
Abortion, SpontaneousAcetylcysteineAntioxidantsCalciumCalcium, DietaryCopperDietary SupplementsFemaleFood, FortifiedHumansHypertension, Pregnancy-InducedManganeseMaternal MortalityPre-EclampsiaPregnancyPrenatal CareRandomized Controlled Trials as TopicSeleniumVitaminsZinc
Study Links
Quality Scores
SafetyNot Assessed
Efficacy65/10
Quality70/10
Citation Metrics
Total Citations19
Citations/Year2.4
Relative Citation Ratio1.05
NIH Percentile52%
Research Impact Scores
APT Score0.75
Weight Score1.60
Normalized Score0.60
Related Supplements
Calcium supplementation commencing before or early in pregna... | Panacea Index