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Meta-Analysis
. 2024 Nov 19;11(11):CD007079.
doi: 10.1002/14651858.CD007079.pub4.

Calcium supplementation (other than for preventing or treating hypertension) for improving pregnancy and infant outcomes

Kiattisak Kongwattanakul  1 , Chatuporn Duangkum  1 , Chetta Ngamjarus  2 , Pisake Lumbiganon  1 , Anna Cuthbert  3 , Jo Weeks  3 , Jen Sothornwit  1
Affiliations
Meta-Analysis

Calcium supplementation (other than for preventing or treating hypertension) for improving pregnancy and infant outcomes

Kiattisak Kongwattanakul et al. Cochrane Database Syst Rev. .

Abstract

Background: Maternal nutrition during pregnancy is known to have an effect on fetal growth and development. It is recommended that women increase their calcium intake during pregnancy and lactation, although the recommended dosage varies among professionals. Currently, there is no consensus on the role of routine calcium supplementation for pregnant women other than for preventing or treating hypertension.

Objectives: To determine the effect of calcium supplementation on maternal, fetal and neonatal outcomes, excluding women with multiple gestation (other than for preventing or treating hypertension), including the occurrence of adverse effects.

Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (which includes results of comprehensive searches of CENTRAL, MEDLINE, Embase, CINAHL, two trials registers and relevant conference proceedings) on 3 December 2022. We also searched the reference lists of retrieved studies.

Selection criteria: We considered all published, unpublished and ongoing randomised controlled trials (RCTs) comparing maternal, fetal and neonatal outcomes in pregnant women who received calcium supplementation versus placebo or no treatment. Cluster-RCTs were eligible for inclusion but none were identified. Quasi-RCTs and cross-over studies were not eligible for inclusion.

Data collection and analysis: Two review authors independently assessed trials for inclusion. At least one review author assessed trials meeting the inclusion criteria for trustworthiness, consulting another review author in cases that were not immediately clear. Two review authors independently assessed the studies for risk of bias, extracted data, and checked trials for accuracy. We assessed the certainty of the evidence using GRADE.

Main results: Twenty-one studies met the inclusion criteria, but only 19 studies contributed data to the review. These 19 trials recruited 17,370 women, with 16,625 women included in the final analyses. The trials were generally at low risk of bias for randomisation and allocation concealment. We chose three outcomes for GRADE assessment: preterm birth less than 37 weeks, preterm birth less than 34 weeks and low birthweight (less than 2500 g). All trials compared calcium supplementation with placebo or no treatment with 17 trials comparing high-dose calcium (greater than 1000 mg/day). Calcium supplementation probably slightly reduces the risk of preterm birth less than 37 weeks (average risk ratio (RR) 0.80, 95% confidence interval (CI) 0.65 to 0.99; 11 trials, 15,379 women; moderate-certainty evidence), but probably has little effect on the risk of preterm birth less than 34 weeks (average RR 1.03, 95% CI 0.79 to 1.35; 3 trials, 5569 women; moderate-certainty evidence), and may have little or no effect on low birthweight (less than 2500 g) (average RR 0.93, 95% CI 0.81 to 1.07; 6 trials, 14,162 women; low-certainty evidence; 1 study reported low birthweight (less than 2500 g) but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 5 studies rather than 6). We downgraded the evidence for imprecision (wide CIs crossing the line of no effect) and inconsistency (high levels of heterogeneity between the studies). There was no evidence that calcium supplementation had any effect on maternal weight gain during pregnancy; increasing bone mineral density in pregnant women; rate of intrauterine growth restriction; perinatal mortality; stillbirth or fetal death rate; increase birth length or fetal head circumference; and adverse effects such as postpartum haemorrhage, gall stones, gastrointestinal symptoms, headache, urinary stones, urinary tract infection or impaired renal function.

Authors' conclusions: This review indicates that calcium supplementation probably reduces preterm birth before 37 weeks. There are no clear additional benefits to calcium supplementation in preterm birth before 34 weeks or prevention of low birthweight. Large multicentre trials to detect the effect of calcium supplementation on fetal birthweight and preterm birth before 34 weeks as the primary outcomes are needed. Further research into the short- and long-term effects of calcium supplementation would also be beneficial.

Trial registration: ClinicalTrials.gov NCT00320125.

PubMed Disclaimer

Conflict of interest statement

KK: none.

CD: none.

CN: none.

PL: none.

AC: was employed by the Cochrane Pregnancy and Childbirth Group, at the University of Liverpool, for a project that included work on this review. The project was also funded by the Children's Investment Foundation Fund (CIFF). Anna Cuthbert has no conflicts of interest to declare.

JW: was employed by the University of Liverpool for a project that included the work on this review. The project was also funded by the Children's Investment Foundation Fund (CIFF). Jo Weeks has no conflicts of interest to declare.

JS: none.

Figures

1
1
Process for using the Cochrane Pregnancy and Childbirth criteria for assessing the trustworthiness of a study.
2
2
Study flow diagram.
3
3
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
4
4
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
5
5
Funnel plot of comparison: 1 Calcium supplementation versus placebo or no treatment (maternal outcomes), outcome: 1.1 Preterm birth < 37 weeks' gestation.
1.1
1.1. Analysis
Comparison 1: Calcium supplementation versus placebo or no treatment (maternal outcomes), Outcome 1: Preterm birth < 37 weeks' gestation
1.2
1.2. Analysis
Comparison 1: Calcium supplementation versus placebo or no treatment (maternal outcomes), Outcome 2: Preterm birth < 37 weeks' gestation by dose of calcium
1.3
1.3. Analysis
Comparison 1: Calcium supplementation versus placebo or no treatment (maternal outcomes), Outcome 3: Preterm birth < 37 weeks' gestation by started to take calcium
1.4
1.4. Analysis
Comparison 1: Calcium supplementation versus placebo or no treatment (maternal outcomes), Outcome 4: Preterm birth < 37 weeks' gestation by type of calcium
1.5
1.5. Analysis
Comparison 1: Calcium supplementation versus placebo or no treatment (maternal outcomes), Outcome 5: Preterm birth < 34 weeks' gestation
1.6
1.6. Analysis
Comparison 1: Calcium supplementation versus placebo or no treatment (maternal outcomes), Outcome 6: Maternal weight gain (g/week)
1.7
1.7. Analysis
Comparison 1: Calcium supplementation versus placebo or no treatment (maternal outcomes), Outcome 7: Maternal bone mineral density (g/cm2) – first phalanx (calcium 300 mg)
1.8
1.8. Analysis
Comparison 1: Calcium supplementation versus placebo or no treatment (maternal outcomes), Outcome 8: Maternal bone mineral density (g/cm2) – second metacarpal (calcium 300 mg)
1.9
1.9. Analysis
Comparison 1: Calcium supplementation versus placebo or no treatment (maternal outcomes), Outcome 9: Maternal bone mineral density (g/cm2) – fourth metacarpal (calcium 300 mg)
1.10
1.10. Analysis
Comparison 1: Calcium supplementation versus placebo or no treatment (maternal outcomes), Outcome 10: Maternal bone mineral density (g/cm2) – first phalanx (calcium 600 mg)
1.11
1.11. Analysis
Comparison 1: Calcium supplementation versus placebo or no treatment (maternal outcomes), Outcome 11: Maternal bone mineral density (g/cm2) – second metacarpal (calcium 600 mg)
1.12
1.12. Analysis
Comparison 1: Calcium supplementation versus placebo or no treatment (maternal outcomes), Outcome 12: Maternal bone mineral density (g/cm2) – fourth metacarpal (calcium 600 mg)
1.13
1.13. Analysis
Comparison 1: Calcium supplementation versus placebo or no treatment (maternal outcomes), Outcome 13: Maternal admission to intensive care unit
1.14
1.14. Analysis
Comparison 1: Calcium supplementation versus placebo or no treatment (maternal outcomes), Outcome 14: Maternal death
1.15
1.15. Analysis
Comparison 1: Calcium supplementation versus placebo or no treatment (maternal outcomes), Outcome 15: Mode of birth: vaginal birth
1.16
1.16. Analysis
Comparison 1: Calcium supplementation versus placebo or no treatment (maternal outcomes), Outcome 16: Mode of birth: instrumental vaginal birth
1.17
1.17. Analysis
Comparison 1: Calcium supplementation versus placebo or no treatment (maternal outcomes), Outcome 17: Mode of birth: caesarean section
2.1
2.1. Analysis
Comparison 2: Calcium supplementation versus placebo or no treatment (infant outcomes), Outcome 1: Low birthweight (< 2500 g)
2.2
2.2. Analysis
Comparison 2: Calcium supplementation versus placebo or no treatment (infant outcomes), Outcome 2: Low birthweight (< 2500 g) by starting time of taking calcium
2.3
2.3. Analysis
Comparison 2: Calcium supplementation versus placebo or no treatment (infant outcomes), Outcome 3: Low birthweight (< 2500 g) by type of calcium
2.4
2.4. Analysis
Comparison 2: Calcium supplementation versus placebo or no treatment (infant outcomes), Outcome 4: Stillbirth or fetal death
2.5
2.5. Analysis
Comparison 2: Calcium supplementation versus placebo or no treatment (infant outcomes), Outcome 5: Perinatal mortality
2.6
2.6. Analysis
Comparison 2: Calcium supplementation versus placebo or no treatment (infant outcomes), Outcome 6: Admission to neonatal intensive care unit
2.7
2.7. Analysis
Comparison 2: Calcium supplementation versus placebo or no treatment (infant outcomes), Outcome 7: Birthweight (g)
2.8
2.8. Analysis
Comparison 2: Calcium supplementation versus placebo or no treatment (infant outcomes), Outcome 8: Birth length (cm)
2.9
2.9. Analysis
Comparison 2: Calcium supplementation versus placebo or no treatment (infant outcomes), Outcome 9: Head circumference (cm)
2.10
2.10. Analysis
Comparison 2: Calcium supplementation versus placebo or no treatment (infant outcomes), Outcome 10: Intrauterine growth restriction
2.11
2.11. Analysis
Comparison 2: Calcium supplementation versus placebo or no treatment (infant outcomes), Outcome 11: Neonatal bone mineral density (g/cm2)
3.1
3.1. Analysis
Comparison 3: Calcium supplementation versus placebo or no treatment (adverse outcomes), Outcome 1: Adverse effects of calcium supplementation – maternal cholestatic jaundice
3.2
3.2. Analysis
Comparison 3: Calcium supplementation versus placebo or no treatment (adverse outcomes), Outcome 2: Urinary stones
3.3
3.3. Analysis
Comparison 3: Calcium supplementation versus placebo or no treatment (adverse outcomes), Outcome 3: Urinary tract infection
3.4
3.4. Analysis
Comparison 3: Calcium supplementation versus placebo or no treatment (adverse outcomes), Outcome 4: Renal colic
3.5
3.5. Analysis
Comparison 3: Calcium supplementation versus placebo or no treatment (adverse outcomes), Outcome 5: Impaired renal function
3.6
3.6. Analysis
Comparison 3: Calcium supplementation versus placebo or no treatment (adverse outcomes), Outcome 6: Maternal anaemia
See this image and copyright information in PMC

Update of

References

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References to studies excluded from this review

Adegboye 2020 {published data only}
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Asemi 2012 {published data only}
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CTRI/2016/10/007373 {published data only}
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CTRI/2019/09/021372 {published data only}
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CTRI/2021/03/032434 {published data only}
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IRCT20100102002954N11 {published data only}
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ISRCTN12033893 {published data only}
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ISRCTN25268811 {published data only}
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    1. IRCT2013040810324N12. The effect of vitamin D and calcium plus vitamin D for leg cramps in pregnant women: a randomised controlled trial. trialsearch.who.int/Trial2.aspx?TrialID=IRCT2013040810324N12 (first received 4 May 2013). [CENTRAL: CN-01838148] 10738035
    1. Mansouri A, Mirghafourvand M, Alizadeh Charandabi SM, Najafi M. The effect of vitamin D and calcium plus vitamin D on leg cramps in pregnant women: a randomized controlled trial. Journal of Research in Medical Sciences 2016;21:1-7. [CENTRAL: CN-02111792] 13657354 - PMC - PubMed
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TCTR20221001001 {published data only}
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References to studies awaiting assessment

Aghamohammady 2010 {published data only}
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References to ongoing studies

NCT02338687 {published data only}
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