Causal relationship between 91 inflammatory factors and fetal growth restriction: a bidirectional Mendelian randomization study

PURPOSE: Current studies have indicated a potential association between inflammatory cytokines and Fetal Growth Restriction (FGR), but the causal relationship between specific inflammatory cytokines and FGR remains uncertain. In this study, we used Mendelian randomization (MR) to further investigate the causal link between 91 inflammatory cytokines and FGR. METHODS: We included data from a sample of 14,824 Europeans and FinnGen consortium fetal growth restriction data (4054 cases vs. 226,256 controls) encompassing 91 inflammatory cytokines. The primary analysis method used was inverse-variance weighted (IVW). Additionally, MR Egger, Weighted median, Simple mode, and Weighted mode were utilized as auxiliary analyses to reinforce the final results. Furthermore, sensitivity analysis was conducted to assess the robustness of the data. RESULTS: Our study revealed that C-C motif chemokine 4 (CCL4), C-X-C motif chemokine 1 (CXCL1), Fibroblast growth factor 19 (FGF-19), IL-10, IL-20, IL-24, and Monocyte chemoattractant protein-4 (CCL13) exhibited associations with FGR risk; however, due to horizontal pleiotropy concerns regarding CCL13 it was excluded from further investigation. Conversely, reverse MR results demonstrated no significant association between inflammatory factors and FGR. CONCLUSION: This MR study provides evidence for an association between CCL4,CXCL1,FGF-19,IL-10, IL-20, IL-24, and FGR risk.More research is needed to evaluate the potential role of these cytokines in preventing and treating FGR.