Association between Maternal ABO Blood Group and Preeclampsia: Protocol for an Updated Systematic Review and Meta-analysis (Preprint)

BACKGROUND Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide. ABO blood group phenotypes have been associated with thrombosis, endothelial dysfunction, and inflammation, which are key mechanisms implicated in preeclampsia pathogenesis. Observational studies have reported inconsistent associations between maternal ABO blood group and preeclampsia, and several new studies have been published since the last comprehensive meta-analysis in 2021. OBJECTIVE An updated systematic review and meta-analysis is warranted to provide robust evidence on this association. METHODS This protocol follows the PRISMA-P 2015 guidelines and has been prospectively registered in the Open Science Framework (OSF) under the identifier 10.17605/OSF.IO/E3KTG (https://osf.io/zm4nf). Observational studies (case-control, cohort, and cross-sectional) reporting maternal ABO blood group and preeclampsia outcomes will be included. A systematic search will be conducted in PubMed/Medline, Embase, Scopus, Web of Science, and the Cochrane Library for studies published from January 2000 to October 31, 2025. Grey literature sources including Google Scholar, ProQuest Dissertations, and conference abstracts will also be searched. Two independent reviewers will perform study selection, data extraction, and risk of bias assessment using the Newcastle-Ottawa Scale. A random-effects meta-analysis will be performed to pool odds ratios for each blood group, and heterogeneity will be assessed using Cochran’s Q and I² statistics. Subgroup and sensitivity analyses will be conducted, and publication bias will be evaluated using funnel plots, Egger’s test, and trim-and-fill method. The certainty of evidence will be assessed using the GRADE approach. CONCLUSIONS This review will provide updated evidence on whether maternal ABO blood group is associated with preeclampsia risk. The findings may help determine whether ABO blood group could serve as a risk marker for preeclampsia and inform future research and clinical practice. CLINICALTRIAL OSF 10.17605/OSF.IO/E3KTG