Elevated Plasma Level of Arginine and Its Metabolites at Labor Among Women With Preeclampsia: A Prospective Cohort Study

Abstract

Background Preeclampsia complicates 3-5% of all pregnancies and is associated with higher levels of asymmetric (ADMA) and symmetric (SDMA) dimethylarginines. Dimethylarginines are inhibitors of nitric oxide, which is a uterine smooth muscles relaxant. Women with hypertensive disorders experience a shorter labor duration compared to normotensive women. However, very little is known about the possible biochemical mechanisms behind differences in labor duration. In this study we aimed to investigate if women with preeclampsia had higher levels of arginines (ADMA, SDMA and L-arginine) at labor than controls, and also investigate the association between arginines and labor duration. Methods The study was based on data from the Swedish, Uppsala County population-based, prospective cohort BASIC, between 2009 and 2018. Arginines were analyzed by Ultra-High Performance Liquid Chromatography using plasma samples taken at labor from women with preeclampsia (n=47) and normotensive pregnancy (n=90). We also analyzed inflammation markers CRP, TNF-R1, TNF-R2 and GDF-15. Results Women with preeclampsia had higher levels of ADMA (p<0.001), SDMA (p<0.001), L-arginine (p<0.001), TNF-R1 (p<0.001), TNF-R2 (p=0.03) and GDF-15 (p<0.01) compared to controls. Further, ADMA and SDMA, not inflammation markers, were negatively correlated to labor duration in preeclampsia. No correlations were observed when comparing arginines and inflammation markers. Conclusions Among women with preeclampsia, our novel findings of higher level of arigines, negative correlation of arginines to duration of labor and absence of correlation of arginines to inflammation markers might support the theory that it is not inflammation but arginines which could be associated with shorter duration of labor in preeclampsia.