New evidence questions the benefit of calcium supplements in pregnancy for preventing pre-eclampsia

An updated Cochrane review has found that calcium supplementation has no effect on pre-eclampsia, challenging long-held assumptions about the role of calcium in preventing hypertensive disorders in pregnancy.

Researchers from Stellenbosch University have found strong evidence from large trials that calcium supplementation during pregnancy does not reduce the risk of pre-eclampsia.

Pre-eclampsia is a life-threatening condition that can affect women in the second half of their pregnancy. It can be fatal or cause lifelong complications for both mother and baby. Pre-eclampsia is characterised by new onset high blood pressure with end-organ injury. The only cure is to deliver the baby. If the mother develops pre-eclampsia with life-threatening complications, then pre-term delivery is the only option. 

Calcium supplementation has long been considered a potential preventive measure, especially in settings with low calcium intake. Current World Health Organization (WHO) guidelines recommend daily calcium supplementation in such populations. However, evidence supporting this approach has always been mixed, and this review raises further doubts.

Findings cast doubt over benefits of calcium during pregnancy

The updated review included 10 randomized controlled trials with 37,504 participants, looking at the effect of calcium supplementation compared to placebo and comparing high- versus low-dose supplementation. 

Results show that there is high certainty evidence from large trials that calcium supplementation during pregnancy has no effect on preventing pre-eclampsia. 

Even when comparing low and high doses of calcium, outcomes remained largely unchanged. Maternal deaths were rare in the studies, and evidence on other critical outcomes such as neonatal death and severe complications was highly uncertain.

“By applying rigorous and transparent review methods, we found no meaningful difference in key outcomes such as pre-eclampsia, maternal death, preterm birth or neonatal mortality,” says Anke Rohwer, author of the review. “Many of the older studies were of very low quality, and re-evaluating them was essential to ensure that current guidance is based on reliable, up-to-date evidence.”

Untrustworthy and small studies pollute earlier evidence

A previous review update had included far more studies, some of which are now excluded due to changes in eligibility criteria, lack of trustworthiness, or methodological flaws. Earlier analyses that included these small or unreliable studies suggested a stronger protective effect of calcium supplementation.

The authors highlighted that small-study effects and publication bias strongly influenced earlier conclusions. Once these biases were addressed, the apparent benefits of calcium supplementation disappeared. 

“Our updated analysis shows that once you account for issues like small-trial effects and publication bias, the evidence supporting calcium supplementation to prevent pre-eclampsia simply doesn’t hold up,” says Professor Catherine Cluver, co-author of the review. “This marks a major shift from earlier reviews, and it’s crucial that clinicians and policymakers understand how much the evidence base has changed.”

For years, calcium supplementation has been recommended as a preventive measure, especially in populations with low dietary calcium intake. However, this updated review suggests that such benefits may be far less significant — and potentially absent — once untrustworthy evidence is removed.

“This review highlights the importance of applying trustworthiness checks to primary research. Unreliable trials can skew the results of systematic reviews and distort scientific consensus,” adds Professor Cluver. “After excluding unreliable studies, we found that the supposed benefit of calcium supplementation on pre-eclampsia disappeared. We are now show that calcium supplementation does not prevent pre-eclampsia, based on large, reliable trials."

The authors assessed trustworthiness of included studies using the TRACT checklist. Similar tools have since been developed, such as INSPECT-SR,  designed to identify problematic studies. Problematic studies include those affected by human error or research misconduct, where reviewers are not confident that the results are reliable.