In pregnant women with low dietary calcium intake, should calcium supplementation of about 1000 mg elemental calcium daily be recommended to prevent hypertensive disorders such as pre‑eclampsia?

Calcium Supplementation in Pregnancy for Preeclampsia Prevention

Yes, pregnant women with low dietary calcium intake should receive 1000-1500 mg of elemental calcium daily to prevent preeclampsia and hypertensive disorders of pregnancy. 1

Primary Recommendation

The WHO strongly recommends calcium supplementation for pregnant women in populations with low dietary calcium intake, as this intervention prevents approximately 50% of preeclampsia cases. 2, 1 This represents the first evidence-based nutritional intervention to prevent preeclampsia, a leading cause of maternal mortality globally. 2

Target Population

• Implement calcium supplementation when habitual dietary calcium intake is unknown or likely <900 mg/day, which applies to most low- and middle-income populations. 1
• In populations where dietary calcium has been studied, 35 of 42 studies found mean intake <900 mg/day, consistent across Asia, Africa, and Latin America. 2
• Do not wait for dietary intake assessment data before implementing supplementation, as limited data should not impede implementation in at-risk populations. 1

Optimal Dosing Protocol

Dose Selection

Prescribe 1.0-1.5 g of elemental calcium daily, depending on local dietary calcium intake, logistical feasibility, and acceptability. 2, 1 While WHO guidelines recommend 1.5-2.0 g daily 2, practical implementation considerations support the 1.0-1.5 g range as effective and more feasible. 2

Formulation and Administration

• Use calcium carbonate as the preferred formulation due to lower cost and high bioavailability (40% elemental calcium). 1, 3
• Administer in divided doses of no more than 500 mg elemental calcium per dose, as single doses above 500 mg are poorly absorbed. 1
• This translates to 2-3 doses per day for optimal absorption. 1
• Consider calcium citrate for patients with GERD or gastrointestinal sensitivity, though it can be taken with or without food. 1

Timing

• Start supplementation from the earliest contact in pregnancy and continue until delivery. 2, 1
• The WHO recommends starting from 20 weeks gestation onwards 2, but earlier initiation is prudent for ease of prescribing and adherence. 2
• Starting 3-6 months before conception ensures adequate maternal mineral stores for continuous fetal mineral accretion. 4

Critical Practice Point: Co-Administration with Iron

Calcium and iron-folic acid supplements can and should be taken together. 4, 1 This is a crucial implementation detail that differs from older guidance:

• While calcium acutely inhibits iron absorption in laboratory studies, this translates to minimal clinical effects. 2, 4
• Do not counsel women to separate calcium and iron supplements by several hours, as this creates an unnecessarily complex regimen that reduces adherence. 2, 1
• Simplifying the regimen by allowing concurrent administration facilitates adherence without compromising iron status. 2

Clinical Benefits

Maternal Outcomes

• High blood pressure is reduced by 30% (RR 0.70) with calcium supplementation in populations with low dietary calcium. 5
• Preeclampsia risk is reduced by 52% overall (RR 0.48), with even greater effects in high-risk women (78% reduction, RR 0.22) and those with low baseline calcium intake (64% reduction, RR 0.36). 5
• Maternal death or serious morbidity is reduced by 20% (RR 0.80). 5
• Improved maternal bone mineral density postpartum. 6

Neonatal Outcomes

• Lower risk of preterm birth in populations with low calcium intake. 3, 6
• Longer pregnancy duration and higher neonatal birth weight. 6

Safety Considerations

The benefits of calcium supplementation substantially outweigh the risks, considering the magnitude and severity of preeclampsia-related maternal and perinatal mortality. 1

Potential Adverse Effects

• Ensure total daily calcium intake (diet plus supplements) does not exceed 2000-2500 mg to avoid adverse effects. 1
• Common side effects include constipation and bloating, which are generally mild. 1
• Calcium supplements modestly increase kidney stone risk (RR 1.17). 1
• One trial noted increased HELLP syndrome (RR 2.67), though this finding requires further investigation. 5

Evidence Quality and Nuances

The recommendation is based on moderate quality evidence from multiple randomized controlled trials involving over 15,000 women. 2, 5 However, important nuances exist:

• Effect size varies by baseline calcium intake: The greatest benefits occur in populations with low dietary calcium (<900 mg/day), where preeclampsia risk is reduced by 64-68%. 5, 7
• In populations with adequate calcium intake (>900 mg/day), the effect is much smaller (RR 0.86 for preeclampsia). 7
• There is heterogeneity in trial results, with less effect observed in larger trials. 5
• Lower doses (500 mg/day) are being studied and may prove sufficient, which could simplify implementation, though current evidence supports 1000-1500 mg daily. 3

Common Pitfalls to Avoid

• Do not delay implementation waiting for local dietary assessment data in populations where low calcium intake is likely. 1
• Do not recommend separating calcium from iron supplements, as this creates unnecessary complexity. 2, 1
• Do not use retinol form of vitamin A concurrently during pregnancy due to teratogenicity risk; beta-carotene form is preferred. 4
• Do not prescribe single doses exceeding 500 mg elemental calcium, as absorption is poor above this threshold. 1

Implementation in Resource-Limited Settings

Despite strong evidence and WHO recommendations, only 29 of 92 countries with published antenatal care guidelines include calcium supplementation recommendations, with most being upper-middle or high-income countries. 8 This represents a critical implementation gap where the intervention is most needed. 8

Calcium supplementation is a low-risk, relatively inexpensive preventive intervention suitable for widespread implementation in community-based and primary-care settings, with substantial potential effects on maternal and newborn health. 2