Highlights
- Recent meta-analyses demonstrate that calcium supplementation during pregnancy may result in little to no difference in the incidence of pre-eclampsia when compared to placebo, especially in large, high-quality trials.
- Evidence regarding calcium’s effects on maternal mortality, perinatal loss, and preterm delivery is uncertain or indicates minimal impact.
- Low-dose and high-dose calcium supplementation appear similarly effective in preventing hypertensive disorders in pregnant women with low baseline dietary calcium intake.
- Concurrent supplementation of calcium and low-dose aspirin shows promising synergistic benefits in reducing pre-eclampsia and adverse pregnancy outcomes in high-risk women.
Background
Hypertensive disorders of pregnancy, including pre-eclampsia, remain a major cause of maternal and perinatal morbidity and mortality globally. Pre-eclampsia affects approximately 2-8% of pregnancies worldwide, contributing to significant adverse outcomes such as maternal death, preterm birth, fetal growth restriction, and perinatal death. Calcium supplementation has been proposed as a simple, cost-effective measure to mitigate this risk, especially in populations with low dietary calcium intake. This update synthesizes evidence from randomized controlled trials (RCTs) and meta-analyses published or updated through early 2025 evaluating calcium supplementation during pregnancy and its impact on hypertensive disorders and related maternal and child outcomes.
Key Content
Clinical Evidence from Randomized Controlled Trials and Meta-Analyses
Calcium Supplementation Versus Placebo
A comprehensive Cochrane systematic review (Cluver et al., 2025) including 10 RCTs with 37,504 women assessed the effect of calcium supplementation compared to placebo or standard care. The analysis revealed that calcium likely results in little to no difference in risk of pre-eclampsia (RR 0.83; 95% CI 0.67 to 1.04; low-certainty evidence). Sensitivity analyses restricting to larger trials (≥500 participants) yielded a relative risk closer to unity (RR 0.92; 95% CI 0.79 to 1.05) with high-certainty evidence supporting minimal clinical effect.
Regarding other maternal outcomes, the effect on maternal death remains very uncertain due to the rarity of events (RR 0.33; very low-certainty). Similarly, calcium probably causes little to no difference in the composite maternal death or severe morbidity outcome (RR 0.80; moderate-certainty).
For perinatal outcomes, calcium supplementation may result in little to no difference in perinatal loss (RR 0.93; low-certainty) and probably little to no difference in stillbirth (RR 0.91; moderate-certainty). The effect on preterm delivery before 37 weeks is uncertain but sensitivity analyses indicate little to no difference (RR 0.97; high-certainty).
Adverse effects related to calcium supplementation are infrequently reported, with very low-certainty evidence precluding conclusions.
Low-Dose Versus High-Dose Calcium Supplementation
Two large RCTs (totaling over 22,000 women) compared low-dose (<1 g/day) and high-dose (≥1 g/day) calcium regimens. Results showed little to no difference in pre-eclampsia incidence (RR 0.96; 95% CI 0.73 to 1.25; low-certainty). Similarly, no differences were observed for perinatal loss, stillbirth, or preterm birth, with evidence ranging from moderate to high certainty. Importantly, low-dose regimens may offer comparable efficacy with improved tolerability and adherence.
Calcium Supplementation Commenced Before Pregnancy
One large multicenter RCT studied calcium supplementation initiated before conception and continued into early pregnancy in women at high risk for pre-eclampsia. Calcium showed little to no difference in the composite outcome of pre-eclampsia or pregnancy loss (RR 0.85; low-certainty). Sensitivity analysis limited to women who conceived suggested a slight potential reduction. Overall, evidence is insufficient to endorse routine preconception calcium supplementation for pre-eclampsia prevention.
Combination with Other Interventions
Emerging evidence from meta-analyses indicates that combining low-dose aspirin with calcium supplementation enhances prevention of pre-eclampsia and related adverse outcomes compared to aspirin alone, notably reducing gestational hypertension, preterm birth, and fetal growth restriction. These findings suggest synergistic mechanisms warranting further investigation and consideration in clinical guidelines for high-risk pregnancies.
Additional Observations from Related Studies
– Observational and shorter-term studies suggest calcium supplementation improves maternal and neonatal outcomes in populations with low baseline calcium intake.
– Calcium’s role in modulating blood pressure regulation via vascular smooth muscle function supports its mechanistic plausibility.
– The interaction between calcium and iron supplementation is complex but does not appear clinically significant for anemia risk when both are administered during pregnancy.
Expert Commentary
Calcium supplementation during pregnancy has been conventionally recommended in some settings, particularly where dietary calcium intake is inadequate, aiming to reduce pre-eclampsia incidence. However, recent high-quality evidence challenges the robustness of this benefit when assessed exclusively by large, rigorously conducted RCTs. The Cochrane review update underscores that calcium supplementation, compared to placebo, may not significantly reduce pre-eclampsia incidence or improve other critical maternal and neonatal outcomes. Notably, sensitivity analyses with larger trials provide higher certainty suggesting negligible effects.
Discrepancies across studies may be attributable to differences in baseline calcium intake, trial quality, population risk profiles, and timing/dose of supplementation. Network meta-analyses affirm calcium’s comparable efficacy to other prophylactic interventions and highlight that both low and high doses effectively reduce pre-eclampsia risk in low calcium intake populations.
The low incidence of maternal mortality and severe morbidity in trials limits definitive conclusions about calcium’s effect on these endpoints.
Calcium supplementation’s safety profile appears favorable, though adverse events remain underreported. Practitioners should also consider possible interactions with other micronutrients and the importance of comprehensive maternal nutrition.
Guidelines such as the WHO currently endorse calcium supplementation in pregnant women at high risk of pre-eclampsia or with low dietary calcium intake but acknowledge the nuanced evidence. Emerging data supporting combined low-dose aspirin and calcium supplementation warrant further guideline incorporation.
Conclusion
Current evidence indicates that calcium supplementation during pregnancy may result in little to no reduction in pre-eclampsia risk, preterm delivery, or perinatal loss when compared to placebo, especially in well-conducted large trials. Low-dose and high-dose calcium regimens demonstrate similar efficacy in populations with low baseline dietary calcium. Calcium’s impact on maternal mortality, severe morbidity, and neonatal outcomes remains uncertain due to event rarity and limited data.
Combination therapy with low-dose aspirin and calcium shows promise in pre-eclampsia prevention among high-risk pregnant women.
Given the variability of findings and population heterogeneity, routine calcium supplementation should be contextualized by dietary calcium intake levels and individual risk status. Large-scale, high-quality, prospective RCTs evaluating long-term maternal and offspring outcomes, optimal dosing, supplementation timing, and combination interventions are needed to refine guidelines and clinical practice.
References
- Cluver CA, Rohwer C, Rohwer AC. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst Rev. 2025 Dec 3;12(12):CD001059. doi: 10.1002/14651858.CD001059.pub6. PMID: 41330480; PMCID: PMC12672055.
- Zhao M et al. Association between calcium supplementation and gestational hypertension, and preeclampsia: A Meta-analysis of 26 randomized controlled trials. Curr Probl Cardiol. 2024 Mar;49(3):102217. doi: 10.1016/j.cpcardiol.2023.102217. PMID: 38013011.
- Cluver CA, et al. Calcium supplementation commenced before pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst Rev. 2025 Sep 18;9(9):CD011192. doi: 10.1002/14651858.CD011192.pub4. PMID: 40965861; PMCID: PMC12445409.
- Li W, et al. Clinical efficacy of low-dose aspirin combined with calcium in preventing preeclampsia: A systematic review and meta-analysis. Medicine (Baltimore). 2023 Aug 25;102(34):e34620. doi: 10.1097/MD.0000000000034620. PMID: 37653760.
- Nascimento LF, et al. Calcium for pre-eclampsia prevention: A systematic review and network meta-analysis to guide personalised antenatal care. BJOG. 2022 Oct;129(11):1833-1843. doi: 10.1111/1471-0528.17222. PMID: 35596262.
