Introduction:
Preeclampsia-eclampsia (PE) poses serious risks to maternal and fetal health. Inflammatory markers—such as WBC counts, macrophage-related factors (e.g., serum clusters, MIF, CSF proteins, and inflammatory proteins), and procalcitonin—are implicated in PE, but their causal roles remain unclear. This study investigates these potential causal relationships.

Material and methods:
Using summary statistics from the FINNGEN R12 cohort database for outcomes and previously published Genome-wide association studies (GWAS) for a comprehensive panel of circulating inflammatory markers, a two-sample Mendelian randomization (MR) analysis was performed. The primary analytical method was inverse-variance weighted (IVW), supplemented by weighted median, weighted mode, and MR-Egger regression. Sensitivity analyses included MR-Egger, MR-PRESSO, Cochran’s Q test, and leave-one-out analysis to assess pleiotropy, heterogeneity, and the robustness of the findings.

Results:
The IVW method, following rigorous outlier correction and sensitivity analyses, revealed a significant protective causal association between genetically predicted macrophage inflammatory protein-1α (MIP-1α) levels and eclampsia (odds ratio = 0.16, 95% confidence interval 0.05 - 0.46, P<0.001, PFDR=0.024). Conversely, no robust causal associations were observed for other investigated exposures, including circulating white blood cell counts, procalcitonin, other macrophage-related cytokines such as MIP-1β, serum differentiation clusters, MIF, or CSF proteins, with either preeclampsia or eclampsia. After the removal of outliers, no pleiotropic variants were detected. Leave-one-out analysis further confirmed the absence of influential genetic variants, substantiating the robustness of the findings.

Conclusions:
This study supports a significant causal link between MIP-1α levels and Eclampsia, highlighting the role of specific inflammatory pathways in its development.