Epidural-related maternal fever and metabolomic changes: a pilot exploratory study

The causes of intrapartum fever associated with labor epidural analgesia remain unclear. Metabolomics enables the qualitative and quantitative analysis of small-molecule metabolites in living organisms. We aimed to apply metabolomic analysis in this pilot exploratory study to explore the preliminary pathophysiological mechanisms underlying fever during labor epidural analgesia.

Non-targeted metabolomic analysis was performed on plasma samples from parturients in both groups: the control group included parturients who did not develop fever after labor epidural analgesia, and the fever group included parturients with a body temperature ≥ 37.3 °C after labor epidural analgesia. Principal component analysis and orthogonal partial least squares discriminant analysis were performed on the processed data. Model reliability was assessed using 200 permutation tests, and differential metabolites were screened and identified using ultra-high-performance liquid chromatography-quadrupole Orbitrap mass spectrometry.

ChiCTR2500103459; May 29, 2025.

A total of 79 differential metabolites were identified. Glutamate, glutathione, arginine, and metabolites involved in the ammonia and urea cycles showed significant differences between the two groups of parturients. The top enriched pathways were arginine biosynthesis, glutamate metabolism, linoleic acid metabolism, glycerophospholipid metabolism, and the urea cycle.

This pilot study preliminarily observed metabolite alterations in the blood of parturients who developed fever after labor epidural analgesia. Changes in the arginine metabolic pathway may be associated with the development of fever, warranting further large-scale validation.