Preterm birth was not a pre-specified outcome for this recommendation. However:

• Low-certainty evidence from the aforementioned Cochrane review suggests preterm birth (< 37 weeks’ gestation) may be reduced with supplementation with lower dose calcium (one study, 422 women; 12/212 vs 30/210; RR 0.40, 95% CI 0.21 to 0.75) (15).
• A separate Cochrane review has examined the effects of calcium supplementation in pregnancy (other than for preventing or treating hypertension) (17). The review included data from 23 trials involving 18 587 pregnant women and informed the GDG panel for the WHO antenatal care recommendations (2). No effects were identified for prioritized outcomes, however the antenatal care (ANC) recommendation (A3) states that “moderate-certainty evidence shows that high-dose calcium supplementation probably reduces preterm birth (12 trials, 15 379 women, RR 0.81 95% CI: 0.66 – 0.99).” However, the GDG agreed that the effect of calcium on preterm birth is probably not distinct from the effect on preventing pre-eclampsia, as preterm birth is frequently a consequence of pre-eclampsia.

Evidence from a qualitative systematic review of what women want from antenatal care showed that women from high-, middle- and low-resource settings valued having a positive pregnancy experience, the components of which included the provision of effective clinical practices (interventions and tests, including nutritional supplements), relevant and timely information (including dietary and nutritional advice) and psychosocial and emotional support, by knowledgeable, supportive and respectful healthcare practitioners, to optimize maternal and newborn health (high confidence in the evidence) (18).

Pre-eclampsia can increase the risk of adverse outcomes to mother and baby, as well as increase the use of additional interventions and hospital admission. Considering these risks, the GDG considers it unlikely that there would be important variability in how women value this outcome.

The Cochrane review did not include studies or collate data related to cost-effectiveness of calcium supplementation in pregnancy. No cost-effectiveness studies were identified.

The following assumptions are taken from the WHO OneHealth tool:(19)

• Using the MSH International drug price calculator, the unitary cost of 600 mg calcium is 0.0213 USD/tablet
• Thus, 3 × 600 mg tablets per day for 20 weeks is estimated to cost US$ 8.95

The cost of calcium is relatively high compared with other supplements such as iron and folate. The weight and volume of the supplement may have cost and logistics implications with respect to storage and transport for health services. Calcium supplements may be available in other doses (e.g.: 500 mg tablets) (20).

A systematic review assessed global inequities in calcium intake during pregnancy, updating a 2005 systematic review on calcium intake by pregnant women worldwide (13). The review included 105 studies of calcium intake during pregnancy. The weighed arithmetic mean was 948.3 mg/day (95% CI 872.1–1024.4 mg/day) for high income countries and 647.6 mg/day (95% CI 568.7–726.5 mg/day) for LMICs. Considering an estimated average calcium requirement of 800 mg/day, 14 (25.9%) studies from high-income countries report calcium intakes below this value, whereas 39 (76.5%) from LMICs did so.

In LMICs, women who are poor, least educated, and residing in rural areas have lower health intervention coverage and worse health outcomes than the more advantaged women. In the 2015 WHO State of Inequalities Report, antenatal care (ANC) coverage of at least four visits differed by at least 25% between the most and least educated, and the richest and poorest in half the LMICs studied (21). Inequalities in ANC coverage of at least one visit were also demonstrated, though to a lesser extent. It is therefore likely that adverse consequences of calcium deficiency in pregnancy are worse in women living in disadvantaged circumstances. Effective, equitable implementation of this recommendation could potentially reduce health inequities.

None

A systematic review of qualitative research exploring women’s views and experiences of antenatal care suggests that they tend to view antenatal care as a source of knowledge and information and generally appreciate any advice (including dietary or nutritional) that may lead to a healthy baby and a positive pregnancy experience (high confidence in the evidence) (2).

However, calcium carbonate tablets might be unpalatable to many women, as they can be large and have a powdery texture (15). In addition, this intervention usually involves taking three tablets a day, which significantly increases the number of tablets a woman is required to take on a daily basis (in addition to other supplements such as iron and folic acid). These factors could have implications for both acceptability and compliance, which needs to be assessed in a programmatic context.

None

Where there are likely to be additional costs associated with supplementation (high confidence in the evidence) or where the recommended interventions are unavailable because of resource constraints (low confidence in the evidence) women may be less likely to engage with services (2).

In addition to the cost, providing calcium supplements may be associated with logistical issues (e.g. supplements are bulky and require adequate transport and storage to maintain stock in medical facilities) and other challenges (e.g. forecasting). Also, multiple pills are needed to reach the recommended dosage, therefore the feasibility of women using this intervention may be affected.

Qualitative evidence on healthcare providers’ views suggests that resource constraints (lack of supplement availability, and lack of trained staff) may limit implementation (high confidence in the evidence) (2).

None.