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

2024-11-19
The Cochrane database of systematic reviews 2024(11)
- Kiattisak Kongwattanakul
- Chatuporn Duangkum
- Chetta Ngamjarus
- Pisake Lumbiganon
- Anna Cuthbert
- Jo Weeks
- Jen Sothornwit

PubMed: 39560075
DOI: 10.1002/14651858.cd007079.pub4

Study Design

Type: Meta-Analysis
Sample size: n = 5,569
Population: pregnant women
Methods: Cochrane systematic review of randomised controlled trials comparing calcium supplementation versus placebo or no treatment

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We considered all published, unpublished and ongoing randomised controlled trials (RCTs) comparing maternal, fetal and neonatal outcomes in pregnant women who received calcium supplementation versus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.

Research Insights

Calcium→Increased Birth Length
increase birth length or fetal head circumference
Effect
Neutral
Effect size
Small
Dose
greater than 1000 mg/day (high-dose) in 17 of 19 trials
Calcium→Increased Bone Mineral Density
increasing bone mineral density in pregnant women
Effect
Neutral
Effect size
Small
Dose
mostly high-dose (greater than 1000 mg/day)
Calcium→Increased Fetal Head Circumference
increase birth length or fetal head circumference
Effect
Neutral
Effect size
Small
Dose
greater than 1000 mg/day (high-dose) in 17 of 19 trials
Calcium→Increased Maternal Weight Gain During Pregnancy
There was no evidence that calcium supplementation had any effect on maternal weight gain during pregnancy
Effect
Neutral
Effect size
Small
Dose
greater than 1000 mg/day (high-dose) in 17 of 19 trials
Calcium→Increased Total Hip Bone Mineral Density
increasing bone mineral density in pregnant women
Effect
Neutral
Effect size
Small
Dose
greater than 1000 mg/day (high-dose) in 17 of 19 trials
Calcium→Reduced Intrauterine Growth Restriction
rate of intrauterine growth restriction
Effect
Neutral
Effect size
Small
Dose
greater than 1000 mg/day (high-dose) in 17 of 19 trials
Calcium→Reduced Low Birthweight
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)
Effect
Neutral
Effect size
Small
Dose
greater than 1000 mg/day (high-dose) in 17 of 19 trials
Calcium→Reduced Perinatal Mortality
perinatal mortality
Effect
Neutral
Effect size
Small
Dose
greater than 1000 mg/day (high-dose) in 17 of 19 trials
Calcium→Reduced Preterm Birth
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)
Effect
Beneficial
Effect size
Small
Dose
greater than 1000 mg/day (high-dose) in 17 of 19 trials
Calcium→Reduced Preterm Birth Less Than 34 Weeks
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)
Effect
Neutral
Effect size
Small
Dose
greater than 1000 mg/day (high-dose) in 17 of 19 trials
Calcium→Reduced Stillbirth
stillbirth or fetal death rate
Effect
Neutral
Effect size
Small
Dose
greater than 1000 mg/day (high-dose) in 17 of 19 trials
Calcium→Reduced Stillbirth or Fetal Death
stillbirth or fetal death rate
Effect
Neutral
Effect size
Small
Dose
mostly high-dose (greater than 1000 mg/day)

Adverse Events Reported

Calcium→gall stones
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.
Finding
No significant difference
Significant
No
Calcium→gastrointestinal symptoms
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.
Finding
No significant difference
Significant
No
Calcium→headache
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.
Finding
No significant difference
Significant
No
Calcium→impaired renal function
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.
Finding
No significant difference
Significant
No
Calcium→low birthweight
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)
Finding
No significant difference
Magnitude
average RR 0.93, 95% CI 0.81 to 1.07
Significant
No
Calcium→postpartum haemorrhage
There was no evidence that calcium supplementation had any effect on ... adverse effects such as postpartum haemorrhage, gall stones, gastrointestinal symptoms, headache, urinary stones, urinary tract infection or impaired renal function.
Finding
No significant difference
Calcium→postpartum hemorrhage
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.
Finding
No significant difference
Significant
No
Calcium→preterm birth less than 34 weeks
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)
Finding
No significant difference
Magnitude
average RR 1.03, 95% CI 0.79 to 1.35
Significant
No
Calcium→preterm birth less than 37 weeks
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)
Finding
No significant difference
Magnitude
average RR 0.80, 95% CI 0.65 to 0.99
Significant
Yes
Calcium→urinary stones
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.
Finding
No significant difference
Significant
No
Calcium→urinary tract infection
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.
Finding
No significant difference
Significant
No