Trial trustworthiness assessment: commentary on the Cochrane 2025 systematic review on calcium supplementation during pregnancy.

Authors

Maria Regina Torloni, Gabriela Cormick, Alvaro Nagib Atallah

Published in

Reproductive health. Volume 23. Issue 1. Jun 27, 2026. Epub Jun 27, 2026.

Abstract

Hypertensive disorders of pregnancy remain a major cause of maternal and perinatal morbidity and mortality worldwide. Calcium supplementation during pregnancy is recommended by guidelines and the World Health Organization to prevent preeclampsia largely based on successive versions of a Cochrane systematic review (SR). However, the 2025 update of this SR reported that calcium supplementation may result in little to no reduction in preeclampsia risk, a conclusion that diverges from all previous versions. This change was driven primarily by the exclusion from meta-analyses of several previously included trials due to concerns about study trustworthiness.
We critically examine trustworthiness assessments in the 2025 SR and identify inconsistencies in how criteria were interpreted and applied across trials. Using two trials as illustrative examples, we show that concerns related to ethics and effect size were applied inconsistently. We further demonstrate that the same trials were deemed trustworthy and included in another Cochrane SR updated in 2024, on calcium supplementation during pregnancy for related outcomes. Sensitivity analyses illustrate how the inclusion of these two excluded trials would significantly change the pooled effect estimates for preeclampsia in the 2025 SR. We argue that reliance on unvalidated trial trustworthiness assessment tools risks subjective exclusion of evidence, potentially impacting guidelines and policies. We recommend that the review authors reassess all trials excluded from the meta-analyses due to trustworthiness issues and conduct sensitivity analyses to transparently assess their impact on the 2025 SR conclusions and related policy recommendations.

PMID:
42374462
Bibliographic data and abstract were imported from PubMed on 30 Jun 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.