Asymmetric dimethylarginine levels in preeclampsia - Systematic review and meta-analysis

Objective: Preeclampsia (PE) is the leading cause of maternal and perinatal mortality around the world. The impaired function of fetal-placental vasculature is a key factor in PE. Several studies have investigated the connection between PE and endothelial dysfunction. Also, many authors have examined the changes in asymmetric dimethylarginine (ADMA) as a prominent marker of endothelial dysfunction. Our study aim is to review and analyse the connections between PE and ADMA levels. Methods: To obtain data we performed a comprehensive literature search in Pubmed, Embase and Web of Science. Standardized mean differences were used to estimate the differences in ADMA levels. Results: The quantitative analysis included 10 studies reporting a total number of 631 PE and 498 healthy pregnant individuals. We found significantly higher ADMA levels in PE patients compared to controls, when comparing the ADMA levels of the patients to the ADMA levels of the controls (z=5.93, p < 0.001). This difference was present regardless of the measurement method. Regarding the onset of PE, we found significantly higher ADMA levels in patients suffering from early-onset PE when comparing the ADMA levels of the early-onset PE patients to that of the controls (z=2.82, p=0.005). However, we did not find such difference when we compared late-onset PE patients' ADMA levels to controls. Conclusion: ADMA is significantly higher in PE patients than in the controls. Elevated ADMA levels can play a major role in the development of PE, but more research is needed to clarify the connection between the two.