Bold takeaway: Calcium supplementation during pregnancy does not prevent pre-eclampsia, even in large trials, challenging decades of assumptions about its protective role. And this is where the conversation gets nuanced, because legacy studies and guidelines now require careful re-examination.
A recent update to the Cochrane review, led by researchers from Stellenbosch University, indicates that calcium supplementation during pregnancy has no significant effect on reducing the risk of pre-eclampsia. This conclusion comes from a synthesis of large randomized controlled trials involving 37,504 participants, comparing calcium to placebo and high-dose versus low-dose calcium regimens.
Pre-eclampsia is a serious, potentially life-threatening condition that typically emerges in the later stages of pregnancy. It is defined by new-onset hypertension accompanied by evidence of organ dysfunction. The only definitive cure is delivery of the baby. When pre-eclampsia progresses to life-threatening complications, early birth may become necessary to protect the mother.
For years, calcium supplementation has been considered a preventive strategy, particularly in populations with low dietary calcium intake. The World Health Organization has endorsed daily calcium supplementation in such settings. Yet the evidence base for these recommendations has always been mixed, and this new review adds to the growing doubt.
What the updated analysis found
- The review analyzed 10 randomized controlled trials with 37,504 participants, examining calcium supplementation versus placebo and comparing high-dose to low-dose regimens.
- Across the board, there was high-certainty evidence that calcium supplementation during pregnancy does not prevent pre-eclampsia.
- When comparing different doses (low vs. high), the results remained largely unchanged. Overall, maternal deaths were rare, while evidence about other critical outcomes like neonatal death and severe complications was uncertain.
Anke Rohwer of Stellenbosch University emphasizes the robustness of the methods: “By applying rigorous and transparent review processes, we found no meaningful differences in key outcomes such as pre-eclampsia, maternal death, preterm birth, or neonatal mortality.” She notes that many older trials were small or of questionable quality, and re-evaluating them was crucial to ensure current guidance rests on reliable, up-to-date evidence.
Why earlier conclusions differed
Earlier reviews included a broader set of studies, some of which no longer meet current eligibility criteria due to methodological flaws, reduced trustworthiness, or other biases. When these smaller or less reliable studies are excluded, the apparent protective benefit of calcium supplementation tends to vanish. Small-study effects and publication bias had historically skewed the picture in favor of calcium's benefits.
Professor Catherine Cluver, co-author of the review, explains: “Once biases such as small-trial effects and publication bias are accounted for, the evidence supporting calcium supplementation to prevent pre-eclampsia simply does not hold up.” This represents a significant shift from prior conclusions, underscoring the need for clinicians and policymakers to reevaluate recommendations in light of new, more trustworthy data.
Trustworthiness and evolving methodologies
The authors assessed study trustworthiness with the TRACT checklist. Since then, newer tools like INSPECT-SR have been developed to flag problematic studies, including those affected by human error or misconduct, where reliability is uncertain. The goal is to prevent unreliable trials from skewing systematic reviews and clinical guidance.
Bottom line: current, reliable evidence from large trials does not support calcium supplementation as a means to prevent pre-eclampsia. This challenges longstanding guidelines, particularly in settings with low calcium intake, and calls for a reconsideration of preventive strategies.
Source:
Cluver, C. A., et al. (2025). Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database of Systematic Reviews. DOI:10.1002/14651858.cd001059.pub6.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001059.pub6/full.
