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

BACKGROUND: Preeclampsia is associated with higher levels of asymmetric (ADMA) and symmetric (SDMA) dimethylarginines. Dimethylarginines are inhibitors of nitric oxide, a uterine smooth muscles relaxant. Women with preeclampsia experience a shorter labor duration compared with normotensive women. However, very little is known about the possible biochemical mechanisms behind these differences. 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, 2009-2018. 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 such as C-reactive protein, tumor necrosis factor (TNF)-R1, TNF-R2, and growth differentiation factor (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 with controls. Furthermore, 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 arginines, negative correlation of arginines to labor duration, 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 labor duration in preeclampsia.