High miR-200a-3p expression has high diagnostic values for hypertensive disorders complicating pregnancy and predicts adverse pregnancy outcomes.

BACKGROUND: Hypertensive disorders complicating pregnancy (HDCP) are various heterogeneous conditions. microRNA (miR)-200a-3p is involved in HDCP diagnosis. This study explored the effects of miR-200a-3p on HDCP patients. METHODS: A total of 126 singleton HDCP patients including 50 cases of gestation hypertension (GH), 42 cases of mild preeclampsia (MP) and 34 cases of severe preeclampsia (SP), were enrolled as study subjects, and 50 normal pregnant women were selected as the control. Serum miR-200a-3p expression was detected and its efficacy in HDCP diagnosis and grading was evaluated. GH, MP and SP patients were allocated to high/low miR-200a-3p expression groups. The correlation between miR-200a-3p expression and general clinical indexes was analyzed. HDCP patients were allocated to high/low miR-200a-3p expression group and maternal and fetal outcomes were followed up. Effects of miR-200a-3p expression on adverse pregnancy outcome incidence were analyzed. RESULTS: miR-200a-3p expression in the serum of HDCP patients was upregulated. The sensitivity and specificity of serum miR-200a-3p level > 1.201 were 87.3% and 96.0%, respectively. Serum miR-200a-3p level in GH, MP and SP patients was increased with the aggravation of the disease. The cut-off value and area under the curve (AUC) of miR-200a-3p for GH, MP and SP diagnosis were 1.145 and 0.9094 (82.0% sensitivity and 88.0% specificity), 1.541 and 0.8126 (73.8% sensitivity and 76.0% specificity), and 1.866 and 0.7367 (64.7% sensitivity and 76.2% specificity), respectively. Serum miR-200a-3p level was correlated with general clinical indexes, fetal birth weight, systolic to diastolic ratio, and fetal growth restriction incidence. High serum miR-200a-3p expression in HDCP patients was associated with increased adverse pregnancy outcomes. CONCLUSION: High miR-200a-3p expression could help to diagnose HDCP, judge severity and was associated with increased adverse pregnancy outcomes.

Diagnostic value of miR-101 levels in blood and urine of patients with hypertensive disorder complicating pregnancy.

OBJECTIVES: This study explored the miR-101 clinical significance in hypertensive disorder complicating pregnancy (HDCP). METHODS: Pregnant women with gestational hypertension (GH)/mild preeclampsia (mPE)/severe preeclampsia (sPE) were included. The miR-101 levels were measured. Correlation between miR-101 and soluble fmslike tyrosine kinase-1 (sFlt-1), miR-101 predictive value, and factors influencing HDCP grade were evaluated. RESULTS: Serum miR-101 was down-regulated and negatively correlated with sFlt-1. miR-101 was an independent risk factor for HDCP and decreased with HDCP severity. The area under the curve of miR-101 in differentiating GH from mPE and mPE from sPE was 0.7764 and 0.8529. CONCLUSION: Serum miR-101 level may be a biomarker for grading HDCP.

Diagnostic value of serum miR-25-3p in hypertensive disorders in pregnancy.

Hypertensive disorders in pregnancy (HDIP) represent one of the leading causes of maternal and perinatal mortality. microRNA (miR)-25-3p plays roles in HDIP diagnosis. We explored miR-25-3p clinical roles in HDIP. HDIP patients [gestation hypertension (GH), mild preeclampsia (mPE), and severe preeclampsia (sPEz)], and normal pregnant women serving as the control were enrolled. Serum miR-25-3p expression patterns were detected by RT-qPCR. The diagnostic efficacy of miR-25-3p on HDIP was analyzed with a ROC curve. Patients were assigned to the high/low miR-25-3p expression groups according to the median value of miR-25-3p expression. All patients were followed up until delivery, and gestational weeks and pregnancy outcomes were recorded at delivery. The effects of miR-25-3p expression on pregnancy outcomes of GH, mPE, and sPEz patients were analyzed by Kaplan-Meier. miR-25-3p expression in GH, mPE, and sPEz patients was up-regulated. In sPEz patients, systolic and diastolic blood pressure, 24-h urine protein, AST, ALT, GGT, and SCr were increased, and PLT was decreased in the high expression group. High miR-25-3p expression was associated with an increased risk of adverse pregnancy outcomes in PE patients. Collectively, high miR-25-3p expression could aid HDIP diagnosis, and associated with an increased risk of adverse pregnancy outcomes in PE patients.

Serum catestatin level is increased in women with preeclampsia.

Catestatin can inhibit catecholamine release from chromaffin cells and adrenergic neurons. Catestatin can also have a strong vasodilator effect. This may be useful in understanding the pathophysiology of preeclampsia and its treatment. In this study, we investigated the serum catestatin levels in pregnant women with and without preeclampsia. Fifty consecutive women with mild preeclampsia, 50 consecutive women with severe preeclampsia, and 100 consecutive pregnant women with a gestational age-matched (±1 week) uncomplicated pregnancy were evaluated in a cross-sectional study. Mean serum catestatin was significantly increased in the preeclampsia group compared to the control group (290.7 ± 95.5 pg/mL vs. 182.8 ± 72.0 pg/mL). Mean serum catestatin was comparable in mild and severe preeclampsia groups (282.7 ± 97.9 pg/mL vs. 298.7 ± 93.4 pg/mL, p = .431). Serum catestatin levels had positive correlations with systolic and diastolic blood pressure, urea, uric acid, and creatinine. In conclusion, serum catestatin levels are increased in preeclamptic pregnancies compared to gestational age-matched controls.IMPACT STATEMENTWhat is already known on this subject? The role of autonomic nervous system dysregulation in the pathophysiology of preeclampsia is known. The most obvious part of this dysregulation is the sympathetic nervous system activation. The adrenal medulla is one of the locations of the sympathetic nervous system in the body.What do the results of this study add? Serum catestatin levels were found to be correlated with clinical and laboratory data of preeclampsia. This highlights the importance of chromaffin cell secretions in the adrenal medulla in preeclampsia.What are the implications of these findings for clinical practice and/or further research? This study will help understand the role of the adrenal medulla in the autonomic nervous system dysregulation in preeclampsia. Also, control of serum catestatin levels may support the treatment of hypertension in preeclampsia.

Correlation of elevated levels of lipoprotein(a), high-density lipoprotein and low-density lipoprotein with severity of preeclampsia: a prospective longitudinal study.

The aim of this study was to examine a possible association between the levels of total serum cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and lipoprotein(a), and the development of severe preeclampsia. We measured the levels of these lipoproteins in a prospective observational longitudinal cohort study that recruited 50 third-trimester pregnant women with mild preeclampsia at the time of recruitment. Two assessments were performed; the first measurement was at 29-31 weeks of pregnancy (at recruitment), and the second took place 4 weeks later. Patients with BMI 30, those < 20 years of age and those > 35 years of age were not included in the study. Eight mildly preeclamptic women developed severe preeclampsia within 4 weeks. In these patients, lipoprotein(a) level showed a twofold increase. A serum lipoprotein(a) level > 40.5 mg/dL in a mildly preeclamptic patient predicted the development of severe preeclampsia later on in the pregnancy, whereas a serum lipoprotein(a) level > 52.5 mg/dL was a marker of severity with high sensitivity and specificity. We suggest through our results that that lipoprotein(a) level correlates with the severity of the disease.IMPACT STATEMENTWhat is already known on this subject? Changes in blood lipids have been reported in preeclampsia. Abnormal lipoprotein levels are thought to play a role in the pathophysiology of the disease.What the results of this study add? In this study, we showed that a serum lipoprotein(a) level >40.5 mg/dL in a mildly preeclamptic patient predicted the development of severe preeclampsia later on in the pregnancy, whereas a serum lipoprotein(a) level >52.5 mg/dL was a marker of severity with high sensitivity and specificity.What the implications are of these findings for clinical practice and/or further research? Our results suggest that blood lipids, and especially lipoprotein(a), are involved in the pathogenesis of preeclampsia. The lipoprotein(a) level correlates with the severity of the disease. Hence, lipoprotein(a) could be used as a predictor of severe preeclampsia and a marker of the severity of preeclampsia. This should be validated through prospective studies recruiting an adequate sample size.

Should magnesium sulfate be administered to women with mild pre-eclampsia? A systematic review of published reports on eclampsia.

AIM: Magnesium sulfate is an evidence-based anticonvulsant drug used to prevent and control eclampsia. Controversy persists on routine administration of magnesium sulfate in cases of pre-eclampsia without severe features. Our objective was to assess the pattern of blood pressure and maternal symptoms preceding eclamptic seizure based on the current published work. MATERIAL AND METHODS: A comprehensive computer-based publication search was conducted in the African Journals Online, Google scholar, HINARI, PubMed, and MEDLINE databases and the Cochrane library to identify descriptive study reports for blood pressure, severity symptoms or stage of pregnancy during convulsion in women with eclampsia. RESULTS: A total of 59 publications were eligible for this review. Overall, 21,149 eclamptic women from 26 countries were included for the interest of one or more of the selected variables. Out of 18,488 eclamptic women, the proportion of antepartum, intrapartum and post-partum eclampsia was 59%, 20% and 21%, respectively. Out of 3443 eclamptic women, 25% were normotensive; 20% had mild-to-moderate hypertension; 32% had severe hypertension; and 21% were hypertensive but unclassified. Out of 2163 eclamptic women, 66% and 27% had a headache and visual disturbance, respectively, preceding the occurrence of convulsion. Out of 2053 eclamptic women, 25% had epigastric area pain, and out of 1092 women with eclampsia, 25% were asymptomatic. CONCLUSION: Although eclampsia is known to result from severe pre-eclampsia with or without organ function derangement, this review has revealed that a significant number of eclamptic women had either normal blood pressure or mild-to-moderate hypertension immediately before seizure. The findings are apparently in support of initiating magnesium sulfate prophylaxis to all women with mild pre-eclampsia.

Role of vascular endothelial growth factor and placental growth factor expression on placenta structure in pre-eclamptic pregnancy.

AIM: Pre-eclampsia is a hypertensive disease that is characterized by high blood pressure and proteinuria after 20 gestational weeks and complicates 3-8% of all pregnancies. It is classified as either mild or severe pre-eclampsia according to severity, and the aim of this study was to investigate the structural differences between these two classifications. METHODS: Placenta samples were collected from 68 women who underwent cesarean delivery. Total volume of villi and numerical density of vascular endothelial growth factor (VEGF)- and placental growth factor (PIGF)-positive cells were estimated on stereology and evaluated using one-way ANOVA. RESULTS: There was no significantly difference in total villi volumes between the groups (P > 0.05). In contrast, on immunohistochemistry, the numerical density of VEGF-positive cells in severe pre-eclampsia was significantly different to the control and mild pre-eclampsia groups (P<0.05). Additionally, the numerical density of PIGF-positive cells in the mild and severe pre-eclampsia group was significantly higher than in the control group (P<0.01). CONCLUSION: There is no relationship between villi volume and pre-eclampsia, although growth factors play a role in placental changes. The present results were supported by histopathology and several studies in the literature.

miR-27b-3p is Highly Expressed in Serum of Patients with Preeclampsia and has Clinical Significance.

BACKGROUND: Preeclampsia (PE) is defined as a salient complication of late pregnancy. microRNAs (miRNAs) have emerged as critical biological regulators in PE. This study determined miR-27b-3p expression in serum of PE patients and investigated its clinical significance in PE. METHODS: This study enrolled a total of 130 pregnant women, including 90 PE patients (51 mild PE and 39 severe PE) and 40 healthy controls. miR-27b-3p expression in the serum of PE patients and healthy controls was detected using RT-qPCR. The correlation among miR-27b-3p expression and 24-h urine protein, systolic blood pressure (SBP), diastolic blood pressure (DBP), serum creatinine, and fetal birth weight was analyzed using Pearson's correlation coefficient. The targeting relationship between miR-27b-3p and PPARG was verified. PPARG protein level in PE patients was detected using ELISA kits. The predictive efficiency of miR-27b-3p and PPARG in PE was analyzed using the receiver operating characteristic (ROC) curve. RESULTS: Compared to normal pregnant women, PE pregnant women, especially severe PE patients, had higher miR-27b-3p expression. miR-27b-3p was positively correlated with 24-h urine protein, SBP, DBP, and serum creatinine but negatively correlated with fetal birth weight. PPARG was poorly expressed in PE patients and negatively correlated with miR-27b-3p. ROC curve showed that both miR-27b-3p and PPARG had good predictive efficacy on PE. CONCLUSION: miR-27b-3p expression in serum of pregnant women with PE was positively correlated with the severity of PE symptoms, suggesting the involvement of miR-27b-3p in PE occurrence.

Predictive role of neutrophil-to-lymphocyte ratio in preeclampsia: A meta-analysis including 3982 patients.

OBJECTIVE: The predictive role of neutrophil-to-lymphocyte ratio (NLR) for preeclampsia (PE) has been explored in several studies and current evidence seems to be conflicting. The aim of this study is to compare the NLR values of mild and severe preeclampsia with the normotensive pregnant women, in order to explore the predictive role of NLR for preeclampsia and whether the NLR value has significant difference between severe and mild preeclampsia. DESIGN AND METHODS: We systematically searched Pubmed, Embase, Web of Science and Cochrane database for relative literature up to May 2019. The statistical analysis was performed using Stata 12.0 software. RESULTS: Totally 15 eligible studies consisting of 3982 patients were enrolled in our meta-analysis. The NLR value is higher in preeclampsia when compared to healthy pregnant women (3270 women, MD: 1.44, 95% CI [1.04, 1.83]). Furthermore, NLR value is higher in severe preeclampsia than in mild preeclampsia (1287 women, MD: 1.12, 95% CI [0.69,1.56]). CONCLUSIONS: The findings of our meta-analysis suggest that NLR value is higher in preeclampsia patients especially in severe preeclampsia. The NLR might be a useful laboratory marker for clinical prediction and disease severity evaluation of preeclampsia. However, given that the available evidence is mainly drawn from case-control studies, future cohorts are needed in this field to accurately determine optimal timing and cut-off values that may be used in the clinical setting.

Clinical Utility of Weekly Laboratory Testing in the Outpatient Management of Preeclampsia and Gestational Hypertension.

Objective To investigate the utility of obtaining weekly laboratory testing in patients managed as an outpatient for gestational hypertension and preeclampsia without severe features. Study Design A multisite retrospective cohort study was performed evaluating preterm women diagnosed with gestational hypertension/preeclampsia managed in an outpatient setting between gestational ages of 23 0/7 and 36 6/7 . Patients were divided into two groups: weekly laboratory evaluation (laboratories group) and a no laboratories group. The primary study outcome was composite maternal morbidity including more than one of the following: development of severe features, HELLP syndrome, eclampsia, placental abruption, maternal intensive care unit admission, or maternal death. Results A total of 204 patients were included in this study, laboratories group ( n = 120) and no laboratories group ( n = 84). The laboratories group was older (28.8 vs. 26.6 years, p = 0.02), had a higher rate of chronic hypertension (44 [36.7%] vs. 17 [20.2%], p = 0.01), and more often experienced the primary composite outcome (53 [44.2%] vs. 24 [28.5%], p = 0.02). No patients in our cohort were delivered for abnormal laboratory values. Conclusion This study found that weekly laboratory testing may have minimal clinical utility in the outpatient management protocol in monitoring patients with mild gestational hypertension or preeclampsia. Delivery was guided by other clinical factors.

Association of MicroRNA-210 and MicroRNA-155 with severity of preeclampsia.

BACKGROUNDS AND OBJECTIVES: Preeclampsia (PE) is one of the leading causes of maternal and neonatal morbidity and mortality. Preeclampsia is associated with aberrant expression of several MicroRNAs which function as gene regulators. The present study aims to determine the expression of MicroRNA-210 and MicroRNA-155 in Preeclampsia, and to detect the association of MicroRNA-210 and MicroRNA-155 levels with the severity of Preeclampsia. METHODS: The study was carried out on thirty PE pregnant women as the Preeclampsia group compared to twenty healthy pregnant women who served as the control group. The patients were chosen at labor wards from Ain Shams Maternity Hospital during the period from June to December 2016. Preeclampsia group was then subdivided into mild Preeclampsia and severe Preeclampsia subgroups according to the levels of arterial blood pressure with the presence of thrombocytopenia, impairment in liver function, progressive renal insufficiency, pulmonary edema and cerebral or visual disturbance. MicroRNA-210 and MicroRNA-155 were estimated by a quantitative real time polymerase chain reaction (qRT-PCR). Results of this study showed that the levels of MicroRNA-210 and MicroRNA-155 detected in the Preeclampsia group are significantly higher than in the control group. Although MicroRNA-210 levels showed high significant increase in severe PE compared to mild PE cases, there were no significant differences in MicroRNA-155 levels between the two PE subgroups detected. CONCLUSIONS: MicroRNA-210 may be the noncoding RNA at the molecular level in which the increase in its level accompanies the progression of PE; and is closely associated with the severity of Preeclampsia.

IMA and IMAR in serum and saliva of preeclampsia--a preliminary study.

INTRODUCTION: Oxidative stress could play a role in the development of preeclampsia. Ischemia modified albumin (IMA) is a oxidatively modified form of albumin. OBJECTIVE: To evaluate the levels of salivary and serum IMA and IMA: albumin ratio (IMAR) in preeclampsia and with its severity and investigate their correlation with the fetal birth weight. METHODS: This case control study was conducted on 50 preeclamptic (32 mild and 18 severe cases) and 50 normal pregnant controls. Blood and saliva were obtained to measure albumin, IMA and IMAR was calculated. RESULTS: serum and salivary IMA and IMAR were significantly increased in preeclampsia. Although the increase in serum was in accordance with the severity, it was not so in the saliva. Yet, salivary IMAR showed significant difference between controls and mild preeclampsia. There was a negative correlation between IMA and albumin in both serum and saliva. A weak negative correlation was seen between the serum IMAR and fetal birth weight (r = -0.293; p < 0.05), but not with salivary IMAR. CONCLUSION: This study is an evidence for involvement of oxidative stress in the pathogenesis of preeclampsia, which is reflected in serum and saliva. Salivary IMAR could be a better marker for early prediction of preeclampsia.

Endothelial Nitric Oxide Synthase (eNOS) 4a/b and G894T Polymorphisms and Susceptibility to Preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy complication with unknown etiology and its incidence is associated with genetic and environmental factors. There are inconsistent reports related to the role of endothelial nitric oxide synthase (eNOS) 4a/b polymorphism on the risk of preeclampsia development. The aim of the present study was to investigate the possible influence of eNOS 4a/b and its synergism with eNOS G894T polymorphism on the risk of preeclampsia. METHODS: The present case-control study consisted of 179 unrelated women with preeclampsia including 118 with mild and 61 with severe preeclampsia and 96 unrelated women with normal pregnancy as controls. All studied women were from Kermanshah Province of Iran. eNOS 4a/b and G894T genotypes were detected using polymerase chain reaction (PCR), and PCR-restriction fragment length polymorphism (RFLP) methods, respectively. The categorical variables between groups were compared using χ(2) test and the Odds ratios (OR) were obtained by SPSS logistic regression. Statistical significance was assumed at p<0.05 level. RESULTS: The frequency of eNOS a allele was slightly higher in both mild (16.5%) and severe (17.2%) preeclamptic women than controls (15.1%). Also, no significant difference was found between early- and late-onset preeclamptic women regarding the distribution of eNOS 4a/b genotypes. The presence of each allele of eNOS a or T was not associated with the risk of preeclampsia. However, the concomitant presence of both eNOS a and T alleles was associated with a non significant increased risk of severe preeclampsia by 1.77-fold (p=0.35). CONCLUSION: The present study indicates the lack of association between eNOS a and T alleles with the risk of mild preeclampsia and a non significant increased risk of severe preeclampsia in the presence of both alleles which needs to be investigated in a study with larger samples.

Estudio comparativo de la morbimortalidad del producto gestacional en mujeres embarazadas con preeclampsia modera o severa / Comparative study of morbimortality of gestational product in pregnant women with mild or severe preeclampsia

INTRODUCCION: La preeclampsia es una enfermedad exclusiva de la gestación humana, que afecta a la embarazada produciendo una disfunción vascular. OBJETIVO: Comparar la morbimortalidad del producto gestacional en mujeres embarazadas con preeclampsia (PE) moderada o severa. PACIENTES Y METODO: Estudio de tipo no experimental, descriptivo, por causa-efecto, de carácter retrospectivo. La población estudiada correspondió a toda paciente que sufrió PE, subclasificada en dos grupos; pacientes con PE moderada y pacientes con PE severa. El estudio se realizó en la Clínica Hospital del Profesor en el período comprendido entre junio del año 2007 y junio del año 2008. Se analizaron variables clínicas del recién nacido y de la embarazada. Los resultados obtenidos fueron analizados por medio de las pruebas de comparación de medias poblacionales y comparación de proporciones poblacionales. RESULTADOS: De un total de 1680 embarazos registrados en la Clínica Hospital del Profesor, 42 fueron diagnosticados con síndrome hipertensivo del embarazo (SHE), correspondiendo a un 2,5 por ciento. 28 (66 por ciento) correspondieron a PE moderada, 13 (32 por ciento) correspondieron a PE severa. El retardo del crecimiento intrauterino (RCIU) presentó diferencia significativa con un p< 0,05. El sufrimiento fetal agudo (SFA) y la mortalidad fetal, no presentaron diferencia significativa con un p> 0,05. CONCLUSION: Si bien las diferencias clínicas para el diagnóstico de preeclampsia moderada y severa son claras, las complicaciones que pueden traer al producto de la gestación no presentan diferencia, salvo al analizar el RCIU.

INTRODUCTION: Preeclampsia is an exclusive disease of human gestation, that affects pregnant women producing vascular dysfunction. AIM: Compare the morbid-mortality of the gestational product in pregnant women with mild or severe preeclampsia (PE). PATIENT AND METHODS: Retrospective, descriptive, non experimental, cause-effect study. The studied subjects were women that suffered with PE, sub-classified in two groups, mild PE patients and severe PE patients. The study was made in the “Clínica Hospital del Profesor” from June 2007 to June 2008. Different clinical parameters from the newborn and the pregnant were analyzed. The results were analyzed by the comparison of population and population ratio tests. RESULTS: From a total of 1680 pregnant women registred in the “Clínica Hospital del Profesor”, 42 were diagnosed pregnancy-induced hypertension / gestational hypertension, which represents 2.5 percent of all pregnancies. 28 (66 percent) represents to a moderate PE, 13(32 percent) represents to a severe PE. Intrauterine growth restriction presented a significant difference with an p< 0,05. The acute fetal suffering and fetal mortality didn’t have a significant difference with an p> 0,05. CONCLUSION: Although the clinical differences for the diagnose of mild and severe PE are clear, the complications that may ocurre to the product of the pregnancy don’t present a significant difference, except for the intrauterine growth restriction, that presented a significant difference with an alpha = 0,05.