Aspirin for pre-eclampsia: beware of subgroup meta-analysis

Findings from this most recent review by Roberge et al.3 cannot be taken as conclusive, given the relatively small amount of data, and missing data, in the ≤ 16-week subgroup, as well as the potential impact of other factors such as variable outcome definitions for perinatal death and possible systematic differences between the women in the two gestational age subgroups. It would be reassuring to see these data confirmed by the currently available IPD data. We would appeal to the PARIS Collaboration to make these data publicly available to reduce uncertainty in this area. Although multiple subgroup analyses carry the risk of finding significant effects by chance, we feel the current debate justifies further analysis of the IPD data in this case. Finally, we predict an avalanche of small RCTs and subgroup meta-analyses based on biomarker risk factors as the search to find better tests for prediction of preeclampsia continues. Whether women identified in this way benefit from low-dose aspirin will remain unknown for some time. We would, therefore, appeal to those undertaking research in this area to ensure that sample sizes are adequate in order to answer this question with certainty, rather than resorting to subgroup meta-analyses of small trials.