dimethylarginine and Pre-Eclampsia

Patients with preeclampsia have higher circulating asymmetric dimethylarginine (ADMA). However, whether circulating ADMA is elevated before the diagnosis of preeclampsia has not been determined.. 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.. 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 (I2 = 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.. Circulating ADMA is elevated before the development of preeclampsia. Studies are needed to evaluate the predictive efficacy of ADMA for the incidence of preeclampsia.

Topics: Arginine; Biomarkers; Case-Control Studies; Female; Humans; Incidence; Pre-Eclampsia; Pregnancy; Prognosis; Reproducibility of Results; Risk

L-homoarginine (hARG) is involved in nitric oxide biosynthesis, but its role and concentration in preeclampsia (PE) have not been fully revealed. The purpose of this study was to develop and validate a feasible clinical assay to quantify serum hARG, arginine (ARG), asymmetric (ADMA) and symmetric dimethylarginines (SDMA) levels by LC-MS/MS and investigate their differences at different stages of pregnancy with or without preeclampsia. Serum samples were collected from 84 pregnant women without complications (controls), 84 with mild preeclampsia (MPE), and 81 with severe preeclampsia (SPE) at various gestation stages (before the 20th week, during the 20th-28th week or after the 28th week of gestation). No significant difference in ARG levels was observed between PE and controls at any stage (P > 0.05). The serum hARG levels and hARG/ADMA ratios of MPE before the 20th week were higher than those of controls (P < 0.001). ADMA levels of MPE were higher than those of controls during the 20th-28th week (P < 0.01). SDMA levels of SPE were higher than those of MPE (P < 0.01) and controls (P < 0.05) after the 28th week. Elevated serum hARG before the 20th week was identified as an independent predictor for PE (OR = 1.478, 95% CI 1.120-1.950). ROC curve analysis showed serum hARG before the 20th week had a good potential to predict MPE (AUC = 0.875, 95% CI 0.759-0.948). In conclusion, our study indicated that elevated serum hARG and dimethylarginine levels detected by LC-MS/MS might serve as potential biomarkers for the early prediction of PE.

Topics: Arginine; Chromatography, Liquid; Female; Homoarginine; Humans; Pre-Eclampsia; Pregnancy; Tandem Mass Spectrometry

The objective of this study is to investigate maternal serum and neonatal umbilical cord asymmetric dimethylarginine (ADMA) levels in prediction of perinatal prognosis in pregnancies with preeclampsia (PE) and fetal intrauterine growth retardation (IUGR) accompanying PE (PE + IUGR).. Maternal serum ADMA (msADMA) and neonatal umbilical cord ADMA (ucADMA) levels were studied from 34 patients with PE, 25 patients with PE + IUGR, and 30 healthy pregnant controls in this prospective case-control study. Umbilical artery Doppler indices of fetuses, birth weights, Apgar scores, umbilical artery pH measurements of neonates, and admissions to neonatal intensive care unit (NICU) were recorded.. Median msADMA was significantly higher in PE and PE + IUGR groups (p = 0.024 and p = 0.011, respectively), and ucADMA was significantly higher in PE and PE + IUGR groups than the control group (p = 0.029 and p = 0.018, respectively). Median msADMA and ucADMA levels were significantly higher in the PE + IUGR group than the PE group (p = 0.019 and 0.021, respectively). ucADMA levels did not correlate with fetal umbilical arterial blood flow neither in the PE nor in the PE + IUGR group (p = 0.518 and p = 0.892, respectively). None was related with neonatal umbilical artery pH or NICU admission rates.. msADMA and ucADMA correlated with severity of PE. msADMA and ucADMA failed to predict perinatal outcome in patients with PE and PE + IUGR.

Topics: Adult; Arginine; Case-Control Studies; Female; Fetal Growth Retardation; Gestational Age; Humans; Infant, Newborn; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Prospective Studies; Umbilical Arteries; Umbilical Cord; Young Adult

Asymmetric dimethylarginine (ADMA) is a key regulator of nitric oxide production. Elevations of ADMA have previously been associated with endothelial dysfunction in pre-eclamptic women. ADMA is degraded mainly by dimethylarginine dimethylaminohydrolase (DDAH), which is also expressed in placental tissue. Therefore, we measured placental DDAH expression and activity in pre-eclampsia and normal pregnancies in order to determine whether impairment of this enzyme in the pre-eclamptic placenta could contribute to elevations of ADMA levels in these women.. ADMA plasma levels were measured by LC-MS/MS in 18 pre-eclamptic patients and 28 controls. Placental DDAH activity was determined by measuring the degradation of [(2)H(6)]-labeled ADMA in tissue homogenates from placental biopsies in 15 women with pre-eclampsia and 16 controls. Placental mRNA expression of DDAH 1, DDAH 2, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and protein-arginine methyltransferase 1 (PRMT1) was determined in tissue biopsies by RT-PCR.. Placental DDAH activity was almost undetectable in pre-eclampsia, and it was significantly higher in controls. ADMA plasma levels were higher in pre-eclampsia as compared to normal pregnancies (0.51±0.15μmol/l vs. 0.42±0.07μmol/l; p=0.005), and the difference between maternal and fetal ADMA levels (feto-maternal ADMA gradient) was lower in pre-eclampsia (0.63±0.20μmol/l vs. 0.80±0.18μmol/l; p=0.02). Furthermore, mRNA expression levels of DDAH 2 were significantly lower in pre-eclamptic women (p=0.04), while PRMT1 expression levels were the same. In pre-eclampsia, we found only weak correlations between maternal ADMA levels and DDAH 1 (r=-0.41; p=0.22) and DDAH 2 expressions (r=-0.45; p=0.17) but a slightly stronger correlation between DDAH 2 expression and feto-maternal ADMA gradient (r=0.60; p=0.07).. Decreased DDAH activity in the pre-eclamptic placenta might contribute to elevated ADMA levels in these patients.

Topics: Adult; Amidohydrolases; Arginine; Female; Fetal Blood; Gene Expression; Humans; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Placenta; Pre-Eclampsia; Pregnancy; Protein-Arginine N-Methyltransferases; Repressor Proteins; RNA, Messenger; Statistics, Nonparametric

To aim of our study is to support the correlation between blood pressure and asymmetric dimethyl argine (ADMA) concentrations as a possible marker for early diagnosis of the preeclampsia syndrome.. We attempted to calculate in 38 pregnant women with preeclampsia (group A) plasma levels of the main inhibitor to nitric oxide synthase (NOS), which is ADMA, and to compare our findings with the levels of ADMA in 36 non preeclamptic pregnant women (group C) and also with the levels in 29 pregnant women who had a history of preeclampsia in previous pregnancies (group B). Maternal venous EDTA plasma samples of 5 ml were collected and analyzed to measure the ADMA concentrations in each subject. Statistical analysis was performed using the Graph Pad Instat Mann-Whitney test, unpaired, non parametric test, two-tail p values.. There was no statistical difference between the three groups regarding maternal and gestational age (24-32 weeks). There was a significant statistical difference between the three groups regarding ADMA levels. The two-tailed p value between group A and group C (normal group) was < 0.001, between group A and group B < 0.002 and between group B and group C < 0.002.. In conclusion we have observed that ADMA probably fulfills many of the criteria to be characterized as a preeclamptic factor and an accurate cut-off point matched to each week of pregnancy should be determined.

Topics: Arginine; Biomarkers; Case-Control Studies; Female; Humans; Pre-Eclampsia; Pregnancy; Pregnancy Complications