Preeclampsia In Early Pregnancy Research Articles

The role of microRNAs in preeclampsia

AIM: The aim of this study was to review current sources of scientific literature covering the role of miRNAs in preeclampsia.
 BASIC PROVISIONS: MicroRNAs are a class of short RNA nucleotide sequences that are not involved in protein synthesis, but are capable of controlling complex processes such as cell growth, differentiation, stress response, and tissue remodeling, which under certain conditions play a key role in a variety of pathological processes, including preeclampsia. MicroRNAs regulate up to 60% of the human genome. There are three types of placental miRNAs: placenta-specific, placenta-associated and circulating ones. Three miRNA gene clusters, namely chromosome 19 cluster (C19MC), chromosome 14 cluster (C14MC), and miR-371 ~ 373 cluster, encode most placenta-specific miRNAs. C19MC encodes 58 mature miRNAs and is expressed in trophoblast cells in early pregnancy and then, in placental differentiated cells. C14MC encodes 63 mature microRNAs, which are also expressed in trophoblasts. The miR-371~373 cluster only encodes six mature microRNAs expressed in placental differentiated cells and embryonic stem cells. The functions of placenta-specific miRNAs are being actively studied now. It has been established that the action of these microRNAs is associated with proliferation, apoptosis, migration, angiogenesis of trophoblast cells and placentation in early pregnancy. Recently, special attention has been paid to identifying microRNAs as possible predictors of preeclampsia in early pregnancy.
 CONCLUSIONS: Literature data indicate that miRNAs are associated with the pathogenesis of preeclampsia. It has been proven that more than a hundred types of miRNAs are expressed in placental tissues, and some of them can be isolated and detected in peripheral blood and urine in patients with preeclampsia. Studying the miRNA types will allow for determining the most significant prognostic markers for early detection of preeclampsia and developing non-invasive tests.

BLOOD BIOMARKERS TO PREDICT OF THE ONSET AND ADVERSE OUTCOMES OF PREECLAMPSIA : A SYSTEMATIC REVIEW

Background: Pre-eclampsia is one of the most common pregnancy complications, and a major cause of fetal and maternal morbidity and mortality globally. Diagnosis currently takes place in the third trimester based on clinical symptoms. This systematic review sought to determine the blood biomarkers that are associated with pre-eclampsia, and in particular, the biomarkers that could predict pre-eclampsia in early pregnancy. Methods: By comparing itself to the standards set by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. So, the experts were able to make sure that the study was as up-to-date as it was possible to be. For this search approach, publications that came out between 2013 and 2023 were taken into account. Several different online reference sources, like Pubmed and SagePub, were used to do this. It was decided not to take into account review pieces, works that had already been published, or works that were only half done. Result: In the PubMed database, the results of our search brought up 257 articles, whereas the results of our search on SagePub brought up 78 articles. The results of the search conducted for the last year of 2013 yielded a total 198 articles for PubMed and 54 articles for SagePub. In the end, we compiled a total of 5 papers, 4 of which came from PubMed and 1 of which came from SagePub. We included five research that met the criteria. Conclusion: PlGF and sFlt-1 are the most used in clinical practice, even if their specificity and sensitivity do not justify a default implementation into guidelines to screen all pregnant women. Their role is limited to rule-out a diagnosis of pre-eclampsia in women presenting with symptoms highly suggestive of the disease. Therefore, their current application is not useful for an early prediction of pre-eclampsia. Novel lines of research are needed to identify molecules able to detect pre-eclampsia in a timely manner and which have a predictive value high enough to justify the costs associated with routine measurements in the general pregnant population.

Longitudinal profile of high-sensitivity C-reactive protein in women with pre-eclampsia.

C-reactive protein (CRP) is a marker for inflammation and its role as a possible biomarker for an early prediction of pre-eclampsia (PE) is unclear. The present study investigates the levels of high-sensitivity CRP (hs-CRP) longitudinally across pregnancy in women with PE and compares them to women without PE (non-PE). A total of 324 pregnant women [216 non-PE and 108 PE women] were included in this study. Maternal blood was taken at four different intervals (V1 = 11-14 weeks, V2 = 18-22 weeks, V3 = 26-28 weeks, and V4 = at delivery). Maternal serum hs-CRP levels were higher at V1, V2, and V3 (p < .05 for all) in the PE group compared to the non-PE group. The hs-CRP levels were associated with maternal blood pressure throughout pregnancy. Maternal hs-CRP levels did not differ among early and late onset PE. Higher maternal hs-CRP levels were associated with the increased risk of PE in unadjusted model in early pregnancy. However, there was no significance after adjusting for confounding factors. Our findings suggest although the levels of hs-CRP were higher in PE in early pregnancy, they are not associated with an increased risk of PE.

ExoCounter Assays Identify Women Who May Develop Early-Onset Preeclampsia From 12.5 μL First-Trimester Serum by Characterizing Placental Small Extracellular Vesicles.

Preeclampsia is a major cause of maternal and perinatal morbidity and mortality worldwide. Identifying women with high risk of developing preeclampsia in early pregnancy remains challenging. Extracellular vesicles released from the placenta offer an attractive biomarker but have been elusive to quantify. Here, we tested ExoCounter, a novel device that immunophenotypes size-selected small extracellular vesicles <160 nm, for its ability to perform qualitative and quantitative placental small extracellular vesicles (psEV) analysis. To investigate disease-specific and gestational age-specific changes, we analyzed psEV counts in maternal plasma samples taken at each of the 3 trimesters from women who had (1) normal pregnancy (n=3); (2) women who developed early-onset preeclampsia (EOPE; n=3); and (3) women who developed late-onset preeclampsia (n=4) using 3 antibody pairs, CD10-placental alkaline phosphatase (PLAP), CD10-CD63, and CD63-PLAP. We further validated the findings in first-trimester serum samples among normal pregnancy (n=9), women who developed EOPE (n=7), and women who developed late-onset preeclampsia (n=8). We confirmed that CD63 was the major tetraspanin molecule coexpressed with PLAP-a known placental extracellular vesicles marker on psEV. Higher psEV counts for all 3 antibody pairs were detected in the plasma of women who developed EOPE than the other 2 groups in the first trimester, which persisted through the second and third trimesters. Significantly higher CD10-PLAP (P<0.01) and CD63-PLAP (P<0.01) psEV counts were validated in the serum of the first trimester of women who developed EOPE compared with normal pregnancy. Application of the ExoCounter assay developed here could identify patients at risk of developing EOPE in the first trimester, thereby providing a window of opportunity for early intervention.

Predictive Biochemical Factors for Pre-eclampsia in Early Pregnancy

Abstract: Pre-eclampsia (PE) is one of the major pregnancy complications, affecting up to 10 % of all pregnancies in some regions of the world. The clinical diagnosis, characterised by hypertension and proteinuria often late during pregnancy, with the added inability to treat (other than delivery), can lead to significant morbidity and mortality in both mother and unborn foetus. Moreover, as yet, only low dose aspirin administration is accepted as a preventive measure for PE. This puts more pressure to identify diagnostic and prognostic biomarkers of PE from blood or urine for the non-invasive screening of pregnant women before pregnancy becomes complicated. Over the years, a number of DNA and protein molecules, such as cell-free DNA, VEGF, sFLT1, PlGF, PP-13, ADMA, and several other biomarkers, have been linked to specific pathophysiological observations and proposed as predictive markers for PE. However, their reliability and reproducibility have been put to the test by numerous studies. The aim of this review is to cover the key clinical and biochemical features of pregnancies complicated by PE and evaluate the robustness of data gathered from various studies in order to better understand the link between the proposed biomarkers and the development of PE so as to better quantify their relevance in diagnostic or prognostic applications. The overall goal is to use such biomarkers for earlier detection, better molecular monitoring, and, where possible, lessening of symptoms, hopefully leading to a reduction in the yearly PE-related deaths worldwide.

PS-C29-10: WEIGHT GAIN IS ASSOCIATED WITH INCREASED ARTERIAL STIFFNESS IN HIGH-RISK PREGNANT WOMEN

Objective: There have been increasing efforts to establish effective screening tools for preeclampsia in early pregnancy. Arterial stiffness is a composite indicator of vascular health, reflects endothelial dysfunction, and has been shown to be predictive of cardiovascular events in the general population, while it has been noted to be increased at the time for preeclampsia. Pregnancy is characterized by acute weight gain. However, whether pregnancy weight gain can affect arterial stiffness is not known. Therefore, we aimed to investigate the impact of pregnancy weight gain on arterial stiffness in high-risk pregnant women. Design and method: In this prospective longitudinal cohort study, pregnant women (n = 177) in their first trimester (10–13 weeks gestation) who met established clinical criteria for high-risk of preeclampsia were recruited from obstetrics clinics. Arterial stiffness measurements and weight were recorded every 4 weeks throughout pregnancy. Arterial stiffness was measured non-invasively using the validated tonometry-based SphygmoCor System. Results: Continuous variables were analyzed using linear. Analysis adjusted for maternal age showed that an increase in total pregnancy weight gain was significantly associated with increased arterial stiffness during pregnancy (0.213 [95%CI: 0.007, 0.068], p &lt; 0.02). More specifically, an increase in late pregnancy weight gain, from second to third trimester, was significantly associated with an increase in arterial stiffness during pregnancy (adjusted beta: 0.052 [CI: 0.002, 0.102], p &lt; 0.05). Conclusion: An increase in total pregnancy weight gain and more specifically late pregnancy weight gain is associated with an increase in arterial stiffness. This is important as arterial stiffness could be a predictive tool for preeclampsia in clinical practice.

A Study on Sensitivity of Angiogenic Factors as Predictors of Preeclampsia and Role of Aspirin in Preventing Preterm Preeclampsia

Background Preeclampsia is one of the hypertensive disorders of pregnancy causing maternal and perinatal mortality and morbidity. The global burden of Pre-eclampsia and eclampsia is 5-10. The prevalence of preeclampsia-complicating pregnancy in India is 7.8. Early prediction of preeclampsia and prophylactic use of aspirin reduces morbidity and mortality.Objectives To study the role of angiogenic factors and biophysical markers to identify women at high risk for developing preterm preeclampsia. To study the diagnostic value of angiogenic factors as predictors of preterm preeclampsia in early pregnancy. To compare the benefits of prophylactic use of 150mg of Aspirin versus 75mg of Aspirin from 11-16 weeks of gestation in reducing the incidences of preterm preeclampsia.Methods It was a two year study conducted at Rajarajeswari Medical College and Hospital. Data for the study was collected from women attending antenatal clinics at 11 weeks 0days to 13weeks 6days after taking informed consent. Screening for preeclampsia was done using biophysical and biochemical tests. Screen-positive women were grouped randomly into Group A and Group B. They were given 7mg and 150mg aspirin and maternal and fetal outcome was analysed.Results In our study 489.6 women were screened positive for preeclampsia. There were no significant differences between the 75mg aspirin group and the 150mg aspirin group with regard to demographic characteristics. Pre-eclampsia occurred in 27.2 of participants in the 75mg aspirin group compared with 4.1 in the 150 mg aspirin group. There was a significant difference in the incidence of PE p0.0293 its severity and the period of gestation at delivery in the two groups. The positive predictive value of the screening method in our study is 12.7 and the negative predictive value is 91.6.Conclusion Our study showed that screening test was beneficial in identifying high-risk cases but the study population was very less. Early screening and use of prophylactic aspirin reduce the development preterm preeclampsia. Aspirin is a safe economical and easily available drug.

First trimester serum apolipoproteins in the prediction of late-onset preeclampsia

Late-onset preeclampsia occurring after 34 weeks of gestation is the most common form of preeclampsia, but little is known about either etiology or prevention. Current detection methods for preeclampsia in early pregnancy have not shown promising results in detecting late-onset preeclampsia. The aim of this study was to assess whether apolipoproteins in combination with maternal medical history and biophysical factors can be used as an early detection method for late-onset preeclampsia. This nested case-cohort study was based at Odense University Hospital, Denmark. Women attending their first trimester scan were invited to participate if they understood Danish or English, were above the age of 18, and had singleton pregnancies. Blood pressure, maternal medical history, uterine artery pulsatility indices, and blood samples were collected at inclusion. Outcome data were collected from participants’ medical files postpartum, and cases were selected when preeclampsia diagnostics were present. Serum samples were analyzed by targeted mass spectrometry using a biomarker panel consisting of 12 apolipoproteins. Logistic regression analyses were performed and finally receiver operating curves were completed. The cohort consisted of 27 cases and 194 normotensive controls, randomized from 340 eligible participants. Significant differences were found between the two groups’ baseline characteristics but none of the apolipoproteins showed significant difference (p < 0.05). The ROC-curve combining maternal characteristics, mean arterial pressure and two apolipoproteins showed the best sensitivity of 55.5% at a 10% false-positive rate and an area under the curve of 0.873. In conclusion, apolipoproteins did not improve the detection of late-onset preeclampsia in a combined screening model.

Blood biomarkers to predict the onset of pre-eclampsia: A systematic review and meta-analysis

Pre-eclampsia is one of the most common pregnancy complications, and a major cause of fetal and maternal morbidity and mortality globally. Diagnosis currently takes place in the third trimester based on clinical symptoms. This systematic review and meta-analysis sought to determine the blood biomarkers that are associated with pre-eclampsia, and in particular, the biomarkers that could predict pre-eclampsia in early pregnancy. We searched the electronic databases (Medline, Embase, Cochrane Library) from inception up to March 2022. Prospective studies with 1000 or more participants that measured blood biomarkers to predict or diagnose pre-eclampsia have been included in this systematic review. Biomarkers’ measurements were considered from the first up to the third trimester, but not during labor. Data concerning pre-eclampsia, biomarker measurements and study characteristics were extracted. Meta-analysis was performed when possible. We found a total of 43 studies (assessing 62 different biomarkers in 18,170 pregnancies, have been included in this systematic review, and a total of 6 studies (assessing 2 biomarkers have been included in the meta-analysis). Statistical analysis was performed for PlGF and sFlt-1. Mean difference in PlGF levels between pre-eclampsia and healthy pregnancies, appear to increase as the pregnancy progresses. Results of sFlt-1 meta-analysis were inconclusive. No significant publication bias was identified. This is the most comprehensive and up to date systematic review and meta-analysis on this important topic on blood biomarkers for the early prediction of pre-eclampsia. Further This research highlights the urgent needed for further discovery research to identify blood biomarkers that could predict the development of pre-eclampsia.

Identifying preeclampsia-associated genes using a control theory method

Preeclampsia is a pregnancy-specific disease that can have serious effects on the health of both mothers and their offspring. Predicting which women will develop preeclampsia in early pregnancy with high accuracy will allow for improved management. The clinical symptoms of preeclampsia are well recognized, however, the precise molecular mechanisms leading to the disorder are poorly understood. This is compounded by the heterogeneous nature of preeclampsia onset, timing and severity. Indeed a multitude of poorly defined causes including genetic components implicates etiologic factors, such as immune maladaptation, placental ischemia and increased oxidative stress. Large datasets generated by microarray and next-generation sequencing have enabled the comprehensive study of preeclampsia at the molecular level. However, computational approaches to simultaneously analyze the preeclampsia transcriptomic and network data and identify clinically relevant information are currently limited. In this paper, we proposed a control theory method to identify potential preeclampsia-associated genes based on both transcriptomic and network data. First, we built a preeclampsia gene regulatory network and analyzed its controllability. We then defined two types of critical preeclampsia-associated genes that play important roles in the constructed preeclampsia-specific network. Benchmarking against differential expression, betweenness centrality and hub analysis we demonstrated that the proposed method may offer novel insights compared with other standard approaches. Next, we investigated subtype specific genes for early and late onset preeclampsia. This control theory approach could contribute to a further understanding of the molecular mechanisms contributing to preeclampsia.

Predictors of preeclampsia. Screening and prophylaxis in the I trimester of pregnancy

Aim. To examine the current state of the problem of the prediction of preeclampsia in early pregnancy.&#x0D; Materials and methods. The article provides an overview of publications based on search results in electronic resources PubMed, Elibrary, EMBASE and Google Scholar.&#x0D; Results. The currently known predictors of preeclampsia can be divided into biochemical and hemodynamic. A number of markers demonstrate prognostic value already in the early stages of gestation. To predict preeclampsia, algorithms are created. They include various combinations of its predictors and maternal risk factors.&#x0D; Conclusion. Prediction of preeclampsia is gradually moving from theory to practice. The instruments of its early forecasting before the gestational age of 14 weeks 6 days are becoming available. That opens up opportunities for targeted and timely prevention of preeclampsia.

Adipsin of the Alternative Complement Pathway Is a Potential Predictor for Preeclampsia in Early Pregnancy.

ObjectiveThe concentrations of complement proteins (adipsin, C3a, and C5a) and soluble endoglin (sENG) in the plasma were measured in this study, and their value as early-pregnancy predictors and potential diagnostic marker of preeclampsia was assessed, respectively.Experimental DesignPlasma samples were obtained from healthy and preeclampsia pregnant women before delivery for a cross-sectional study. Plasma samples were collected from healthy and preeclampsia pregnant women throughout pregnancy and postpartum for a follow-up study. Enzyme-linked immunosorbent assays were used to detect plasma levels of several complement proteins (adipsin, C3a, and C5a) and sENG.ResultsThe plasma levels of adipsin, C5a, and sENG were significantly increased before delivery in pregnant women with preeclampsia. During pregnancy, the plasma adipsin, C5a, and sENG levels were increased from the third trimester in healthy pregnant women; plasma adipsin levels remained stable after delivery, while C3a levels increased in the second trimester and remained stable afterward. Furthermore, levels of adipsin, C5a, and sENG were higher in preeclampsia patients at different stages of pregnancy; the C3a level presents a similar change and no difference was found in the third trimester. In the first trimester, receiver-operating curve (ROC) curve analysis showed that adipsin (AUC, 0.83 ± 0.06, P=0.001) and sENG (AUC, 0.74 ± 0.09, P=0.021) presented high value as predictors of early pregnancy.ConclusionsAdipsin is likely a novel plasma biomarker to monitor the increased risk of preeclampsia in early pregnancy. Moreover, the increased plasma levels of adipsin, C5a, and sENG before delivery may be associated with preeclampsia.

FIRST-TRIMESTER NEUTROPHIL-TO-LYMPHOCYTE AND PLATELET-TO-LYMPHOCYTE RATIOS AS INDICATORS FOR EARLY DIAGNOSIS OF PREECLAMPSIA

Background: Preeclampsia is a popular obstetric complication. Neutrophil to lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have gained notable attention as systemic inflammatory response indicators in diverse clinical settings. Objective: To evaluate the diagnostic worth NLR and PLR during the first trimester of gestation to forecast the subsequent occurrence of preeclampsia. Patients and methods: The present study was a prospective cohort study that enrolled 300 pregnant ladies. Initial CBC was done for all eligible cases at 7-14 weeks of gestation then cases were followed up till delivery. Results: The results showed progressively statistically increase in the mean NLR in PE cases compared to control cases and a statistically significant difference between the control and PE cases s regard PLR. Cut off value 1.7538 NLR can differentiate normotensive pregnant women from preeclampsia women with sensitivity of 86.5 %, specificity of 91.6% %, PPV of 64 %, and NPV of 97.5 %. However, PLR can differentiate normotensive pregnant women from preeclampsia women at a cut off value 80.70 with sensitivity of 81.1 %, specificity of 95.1 %, PPV of 28.6 %, and NPV of 64.6 %. Conclusion: Neutrophil to lymphocyte ratio and platelet to lymphocyte ratios is cheap, simple, rapid, and readily accessible marker that may be beneficial to predict preeclampsia in early pregnancy. Hence, these easy applicable parameters can be applied as low-cost predictive factors for the development of PE.

The effect of calcium supplementation on blood pressure in non-pregnant women with previous pre-eclampsia: A randomized placebo-controlled study.

Low dietary calcium is associated with the hypertensive disorders of pregnancy, and evidence suggests that the risks associated with pre-eclampsia are reduced by calcium supplementation. In the general (non-pregnant) population, low dietary calcium intake is associated with hypertension with inconsistent evidence that calcium supplementation may reduce blood pressure. Women with pre-eclampsia are also at risk of hypertension later in life. An exploratory sub-study among early participants enrolled in the WHO long-term calcium supplementation in women at high risk of pre-eclampsia (CAP) study reported a trend to more blood pressure reduction with calcium in non-pregnant women with previous severe as opposed to non-severe pre-eclampsia. The current study reports the effects of low-dose calcium supplementation in non-pregnant women in the complete trial cohort. The CAP Study was a multi-country randomized, double-blind placebo-controlled clinical trial to test the hypothesis that calcium deficiency may play a role in the genesis of pre-eclampsia in early pregnancy. From 2011 to 2016, non-pregnant women who had pre-eclampsia or eclampsia in their most recent pregnancy were randomized to receive either 500mg/day elemental calcium or placebo. In this sub-study we compared the change in blood pressure from baseline to the 12-week visit between participants receiving calcium versus placebo for those not pregnant at the 12-week visit. Of 1355 women randomized, 810 attended a 12-week visit without being pregnant, of whom 791 had blood pressure measurements available for both baseline and 12-week visits. There was a greater reduction in blood pressure in the calcium group compared with the placebo group for systolic pressure (difference 3.1mmHg, 95% CI 0.8 to 5.4) and mean arterial pressure (MAP) (difference 2.0mmHg, 95% CI 0.1 to 3.8). The difference in diastolic blood pressure reduction (1.4mmHg, 95% CI -0.5 to 3.3) was not statistically significant (p=0.140). For women with previous pre-eclampsia with severe features (n=447), there was significantly greater reduction in blood pressure in the calcium than the placebo group (difference for systolic 4.0, 95% CI 0.7 to 7.3; diastolic 3.0, 95% CI 0.5 to 5.5 and mean arterial pressure 3.3, 95% CI 0.8 to 5.9mmHg). For women with previous pre-eclampsia without severe features (n=344), there were no significant differences between calcium and placebo groups. ANOVA analysis found no statistically significant interaction between previous pre-eclampsia severity and treatment, for systolic (p=0.372), diastolic (p=0.063) or mean blood pressure (p=0.103). Low-dose calcium supplementation significantly reduced systolic and mean arterial pressure in non-pregnant women with previous pre-eclampsia. We did not confirm a greater calcium effect in women with previous pre-eclampsia with severe versus non-severe features. The effect of low-dose calcium is of importance since even modest blood pressure reductions at a population level may have important benefits in terms of reduced major complications of hypertension. This study adds to the mounting evidence of health benefits which could be achieved for populations with low dietary calcium through strategies to increase calcium intake, particularly among women at high risk due to previous pre-eclampsia. The trial was registered with the Pan-African Clinical Trials Registry, registration number PACTR201105000267371 (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=267).

Role of platelet count and mean platelet volume and red cell distribution width in the prediction of preeclampsia in early pregnancy.

Introduction:Mean platelet volume (MPV), platelet count (PC), and red cell distribution width (RDW) are various blood indices that play important role in preeclampsia. This study aimed to evaluate the role of MPV, RDW, and PC for the prediction of preeclampsia in the early second trimester of pregnancy and to observe its correlation with disease severity.Material and Methods:A prospective case-control study was conducted for 1 year in the Department of Obstetrics and Gynecology. A total of 543 healthy pregnant women were recruited, after obtaining informed consent and ethical clearance and followed till 6 weeks postpartum, 43 were lost to follow-up. Out of 500 women, nonsevere preeclampsia (NSPE) occurred in 16 women and severe preeclampsia (SPE) in 34 women. Around 51 healthy normotensive pregnant women were recruited after systematic randomization from the same cohort, who had not developed the disease, served as controls. NSPE and SPE were defined as per ACOG 2013b guideline. MPV, RDW, and PC were measured two times by the Siemens Advia analyzer; the first samples were withdrawn at the time of enrolment and the next sample was taken after the development of the disease, and both samples were analyzed.Results:MPV was increased with the severity of preeclampsia, diagnostic accuracy was 69.4%, at a cutoff value of ≥9.05 fl and MPV discriminated controls and NSPE with 50.0% sensitivity and 82.4% specificity. To discriminate between controls and SPE, diagnostic accuracy was 74.6% at a cutoff value of ≥9.05 fl, with a sensitivity of 50%. For control versus SPE, MPCs at the cutoff value of ≥2.085 lac/mm3 had sensitivity 52.9% and specificity 66.7%, and diagnostic accuracy 61.2%. For RDW NSPE, at a cutoff value of ≥11.5%, it discriminated against controls and NSPE with 85.3% sensitivity and 49.0% specificity.Conclusion:NSPE, MPV, RDW, and PCs had good discriminatory value with the severity of the disease.

Preeclampsia for the Nephrologist: Current Understanding in Diagnosis, Management, and Long-term Outcomes.

Preeclampsia is a multisystem progressive disorder of pregnancy that can be potentially catastrophic for the mother and the fetus. It involves complex perturbations of the kidney and systemic physiology, along with long-term effects on vascular and kidney health. Thus, the nephrologist plays a key role in the peripartum and long-term management of preeclampsia. Recent translational research has improved our understanding of its pathophysiology, and there is hope for novel therapies. In this review, we discuss the evolution of diagnostic criteria and dilemmas in the diagnosis of hypertensive disorders in pregnancy. We summarize the advances in the pathogenesis and prediction of preeclampsia. We describe the management and prevention of preeclampsia focusing specially on the forthcoming strategies from the nephrologist's perspective. We address the evidence regarding long-term outcomes for the mother and the child. We end with exploring areas warranting future research.

Soluble endoglin in urine as an early-pregnancy preeclampsia marker: antenatal longitudinal feasibility study

This study aimed to evaluate soluble endoglin (sEng) in urine as a preeclampsia predictor. Ninety-three pregnant women at risk for preeclampsia were followed. Spot urine sample ELISA analysis before 20 weeks of gestation was done to assess protein levels. Logistic regression analysis evaluated associations between preeclampsia with sEng/creatinine ratio, pg/mg, adjusted for risk factors. Preeclampsia incidence was 22.8% (20/92). Urinary sEng/creatinine (pg/mg) 0.001 (95% CI 0.001–0.136) was associated, adjusted for body mass index > 28 kg/m2 OR 6.44 (95% CI 1.11–37.47) and mean arterial pressure OR 1.20 (1.07–1.35). During the first half of gestation sEng urinary excretion was lower in pregnant women developing preeclampsia. Impact statement What is already known on this subject? The angiogenesis factors present in the plasma of pregnant women have shown good preclinical predictors of preeclampsia. Studies on urinary markers in pregnancy are infrequent, despite the ease of obtaining urine specimens. What do the results of this study add? Values of the sEng/creatinine ratio during the first half of pregnancy were related to a higher chance of preeclampsia occurring when it was evaluated alone or adjusted by body mass index and mean arterial pressure values. What are the implications of these findings for clinical practice and/or further research? The potential benefits of a urinary test compared to one of the blood levels include its non-invasive nature and ease of performing the test, even during prenatal care. Future research is expected to evaluate the sEng/creatinine ratio relevance to improve clinical scores of preeclampsia prediction for the identification of women at risk for this disease.

From first-trimester screening to risk stratification of evolving pre-eclampsia in second and third trimesters of pregnancy: comprehensive approach.

Preeclampsia and associated hypertensive disorders of pregnancy represent a leading cause of global maternal and neonatal morbidity and mortality. Identification of women at high risk for developing preterm-preeclampsia and prophylaxis with low-dose aspirin has the potential to significantly reduce the rate of preterm-preeclampsia. In addition, risk assessment and monitoring of women in the second and third trimester of pregnancy, to aid in early detection of evolving disease, timely referral to specialist care, and active monitoring of women with confirmed or suspected preeclampsia is essential for improving maternal and neonatal outcomes. The angiogenesis-related biomarkers sFlt-1 and PlGF have been shown to have clinical value to aid in the prediction, diagnosis, and risk stratification of preeclampsia when used either alone or in combination with other risk factors. However, currently there is no consensus on the optimum strategy to link first trimester screening for preterm-preeclampsia with appropriate second and third trimester risk assessment strategies. This opinion paper will outline the current evidence for first trimester preeclampsia screening and prevention, as well as the evidence for various risk stratification approaches for detection of evolving preeclampsia through the second and third trimesters of pregnancy, and proposes a potential model integrating these tools. This article is protected by copyright. All rights reserved.

A Study to Assess the Significance of Urinary Collagen IV Excretion to Predict Preeclampsia in Early Pregnancy

It was a prospective study with a case control design. The purpose of the study was to measure the urinary collagens IV (U-coll IV) and microalbumin (MA) level in early pregnancy and to explore the role of excretion U-coll IV in prediction of preeclampsia (PE). A total number of 119 pregnant women at 10-14 weeks of pregnancy were selected on the basis of availability. MA by immunoturbidimetry assay and U-coll IV by enzyme immunoassay method were measured in these subjects and they were followed up to the term for the possible development of PE. MA was defined by albumin-creatinine ratio (ACR) above 32mg/g and high U-coll IV was defined by values above the cut-off point 2.74 ng/ml determined by the median value of the (controls). The data were analyzed by grouping the subjects who developed PE in later stages of pregnancy (the PE group) and those who did not develop PE in later stages (Control group). From the total subjects, 10 developed PE which shows a prevalence of about 8.4%. The PE group had higher value of ACR as compared to Control [ACR, mg/g, median (range), 42.3]. The sensitivity of ACR in predicting PE was 80%, specificity 49.54%, PPV 12.69% and NPV 96.42% respectively. The sensitivity of high U-coll IV in predicting PE was 70%, specificity 50.5%, PPV 11.5% and NPV 94.8%. It may be concluded that early pregnancy levels of MA and U-coll IV can be used as predictors of PE with high negative predictive value; and U-coll IV has no added advantage over MA in this respect.

Efficiency of placental three dimentional power Doppler ultrasonography for predicting preeclampsia in early pregnancy

Purposeto evaluate the role of three dimentional power doppler ultrasonography (3D PDUS) of the uteroplacental circulation in early pregnancy as a screening tool for prediction of preeclampsia. Patients and methods50 pregnant women who came to do routine ultrasound scan between 11 and 13.6 weeks of pregnancy during the period from February 2016 to April 2016. Placental volume and vascularization indices were obtained, and vascular index (VI), flow index (FI), blood vessels and blood flow index (VFI) were calculated by three-dimensional Doppler histogram. ResultsOf the included 50 pregnant women, 22% developed preeclampsia and 78% did not develop preeclampsia. The placental blood flow perfusion in patients with pre-eclampsia had a lower VI, FI and VFI compared to non preeclamptic women with highly significant statistical difference (P < 0.001) Conclusion3D PDUS can be used as an effective screening tool to predict preeclampsia in early pregnancy.