Abstract
OBJECTIVE: To investigate the alterations in lipid metabolites and circulating inflammatory factors associated with preterm birth, elucidate their interactions, and uncover the underlying pathophysiologic mechanisms. By identifying potential predictive biomarkers and informing the development of effective therapeutic interventions, this research seeks to improve maternal and neonatal health outcomes. METHODS: This study included 179 lipid species (n = 7174) and 91 circulating inflammatory factors (n = 14 824) as exposure variables, with preterm birth data from the FinnGen database (n = 186 212) serving as the outcome variable. We applied a two-sample Mendelian randomization approach and mediation analysis techniques to identify specific biomarkers causally associated with preterm birth and to investigate the relationships between them from a genetic perspective. RESULTS: In this study, we identified 11 lipid metabolites that show a significant causal association with preterm birth, of which eight are positively correlated and three are negatively correlated. Additionally, we identified 18 circulating inflammatory factors with a significant causal relationship to preterm birth, with 10 showing a negative correlation and eight a positive correlation. Adenosine deaminase (ADA) served as a crucial protective factor against preterm birth (P = 0.006, 95% confidence interval [CI] 0.90-0.98) and mediated the causal relationships between various lipid metabolites and preterm birth. CONCLUSION: This Mendelian randomization study identifies dysregulated lipid metabolism and inflammatory pathways influencing preterm birth. It identifies dysregulated lipid metabolism and inflammatory pathways influencing preterm birth. ADA is a significant protective factor against preterm birth. Specific phosphatidylcholine subtypes exert their protective effects against preterm birth through an ADA-dependent pathway. The mediation effect was -0.005 (95% CI -0.01 to -0.001). This finding not only deepens our understanding of the inflammatory origins of preterm birth but also provides direct evidence for the development of precision prevention strategies based on the regulation of the lipid-inflammation axis.