Circulating asymmetric dimethylarginine and the risk of preeclampsia: a meta-analysis based on 1338 participants

// Jing Yuan 1, * , Xinguo Wang 2, * , Yudou Xie 3 , Yuzhi Wang 3 , Lei Dong 4 , Hong Li 5 and Tongyu Zhu 3 1 Department of Medical Information, General Hospital of Jinan Military Command, Shandong 250031, China 2 Department of Medical Information, The Jiaotong Hospital of Shandong Province, Shandong 250031, China 3 Department of Obstetrics and Gynecology, General Hospital of Jinan Military Command, Shandong 250031, China 4 Department of Ultrasonic Medicine, General Hospital of Jinan Military Command, Shandong 250031, China 5 Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China * These authors have contributed equally to this work Correspondence to: Tongyu Zhu, email: adep2016@163.com Keywords: preeclampsia, asymmetric dimethylarginine, endothelial function, meta-analysis Received: December 28, 2016     Accepted: February 08, 2017     Published: March 24, 2017 ABSTRACT Background: Patients with preeclampsia have higher circulating asymmetric dimethylarginine (ADMA). However, whether circulating ADMA is elevated before the diagnosis of preeclampsia has not been determined. Methods: A meta-analysis of observational studies that reported circulating ADMA level before the onset of preeclampsia was performed. Pubmed and Embase were searched. Standardized mean differences (SMD) with 95% confidence intervals (CI) were used to estimate the differences in circulating ADMA. A random effect model or a fixed effect model was applied depending on the heterogeneity. The predictive efficacy of circulating ADMA for the incidence of preeclampsia was also explored. Results: Eleven comparisons with 1338 pregnant women were included. The pooled results showed that the circulating ADMA was significantly higher in women who subsequently developed preeclampsia as compared with those did not (SMD: 0.71, p < 0.001) with a moderate heterogeneity (I 2 = 43%). Stratified analyses suggested elevation of circulating ADMA is more remarkable in studies with GA of ADMA sampling ≥ 20 weeks (SMD: 0.89, p < 0.01) as compared those with GA of ADMA sampling < 20 weeks (SMD: 0.56, p < 0.01; p for subgroup interaction = 0.03). Differences of maternal age, study design, and ADMA measurement methods did not significantly affect the results. Only two studies evaluated the potential predicting ability of circulating ADMA for subsequent preeclampsia, and retrieved moderate predictive efficacy. Conclusions: Circulating ADMA is elevated before the development of preeclampsia. Studies are needed to evaluate the predictive efficacy of ADMA for the incidence of preeclampsia.