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Aim: To develop a combined predictive model for preterm and term pre-eclampsia (PE) during the first trimester of pregnancy., Methods: This investigation was a nested case-control study in singleton pregnancies at the Maternal-Fetal Medicine Unit, University of Chile Hospital. A priori risks for preterm and term PE were calculated by multivariate logistic regression analyses. Biophysical markers were log 10 -transformed and expressed as multiples of the median. A multivariate logistic regression analysis was used to estimate a combined predictive model of preterm and term PE. Detection rates at different cut-off points were determined by a receiver operator curve analysis of a posteriori risks., Results: First trimester mean arterial pressure and uterine artery Doppler pulsatility index were significantly higher in women who develop PE than in the unaffected group. The detection rate of preterm PE based on maternal characteristics and biophysical markers was 72% at a 10% false-positive rate, corresponding to a cut-off risk of 1 in 50. The detection rate for term PE was 30% at a 10% false-positive rate., Conclusion: Preterm PE can be predicted by a combination of maternal characteristics and biophysical markers. However, first trimester screening is less valuable for term PE., (© 2018 Japan Society of Obstetrics and Gynecology.)

Objective: The aim of this study was to determine the role of nerve growth factor (NGF) in the first-trimester screening for preeclampsia (PE)., Methods: Uterine artery Doppler (UtAD) was determined transvaginally. Maternal concentrations of NGF were assessed in 42 patients who subsequently developed PE and in 95 controls. Quantile and multivariate regression analyses were performed for the NGF and UtAD adjustment and expressed as the multiple of the median (MoM) of the unaffected group. Logistic regression analysis was conducted to identify the best model for the prediction of PE., Results: The maternal plasma concentration of NGF exhibited a trend towards lower values in patients who subsequently developed early-onset PE (e-PE) compared to controls (10.7 vs. 38.2 pg/ml, respectively; p = not significant). The median MoM NGF in the all-PE, e-PE and control groups was 0.97 (95% CI 0.13-3.36), 0.62 (95% CI 0.16-2.19) and 1.00 (95% CI 0.20-2.94), respectively (p = not significant). The best predictors of PE were previous PE, chronic hypertension and UtAD. With a false-positive rate of 10%, the detection rates (DRs) of all-PE and e-PE were 38 and 50%, respectively. The addition of MoM NGF did not improve the DR of PE., Conclusion: First-trimester NGF tends to be lower in patients who subsequently develop e-PE., (© 2016 S. Karger AG, Basel.)

Telocytes (TC) are a new type of stromal cells initially found and studied in digestive and extra- digestive organs. These cells have a small cell body with 2 to 5 thin and extremely long cytoplasmic prolongations named telopodes. In recent years, TC have also been described in placental chorionic villi, located in a strategical position between the smooth muscle cells from fetal vessels and the myofibroblasts in the stromal villi. Unlike other organs, the placenta is not innervated and considering the strategic location of TC is has been postulated that TC function would be related to signal transduction mechanisms involved in the regulation of the fetal vessels blood flow, as well as in the shortening/lengthening of the chorionic villi, providing the necessary rhythmicity to the process of maternal/fetal metabolic exchange. Preeclampsia (PE) is a systemic syndrome that affects 4%-6% of pregnancies worldwide. It is characterized by a placental state of ischemia-hypoxia which triggers an oxidative stress stage with the concomitant production of reactive oxygen species (ROS) leading to an increase in the degree of placental apoptosis. Placental vascular tone is regulated by the vasodilator nitric oxide (NO) and, in PE cases, NO is diverted towards the formation of peroxynitrite, a powerful oxidative agent whose activity leads to an increase of placental apoptosis degree that compromises TC and myofibroblasts, a key feature we would like to emphasize in this work.

Preeclampsia (PE) is a major health problem occurring in pregnant women and the principal cause of maternal morbidity and perinatal mortality. It is characterized by alteration of the extravilli trophoblast cell migration toward the endometrial spiral arteries with a concomitant reduction in maternal blood flow in the placenta. This result in a state of ischemia-hypoxia which triggers an oxidative stress stage with production of reactive oxygen species. A cascade of cellular and molecular events leads then to endothelial dysfunction, transduction pathway signal disruption and induction of apoptosis and necrosis mechanisms and therefore a significant reduction in the amount of nutrients required for normal fetal development. Placental anchoring chorionic and stem villi present a skeleton of myofibroblasts arranged in parallel disposition to its longitudinal axis. The intraplacental blood volume is controlled by the contraction/relaxation of these myofibroblasts, promoting the delivery of nutrients and metabolites to the fetus. Recently, a new mesodermal originated cell type has been described in the villous stroma, the so named "telocytes". These cells are strategically located between the smooth muscle cells of the blood vessel wall and the myofibroblasts, and it is reasonable to hypothesize that they may play a pacemaker role, as in the intestine. This study provide new information supporting the notion that the occurrence of oxidative stress in PE is not only related to endothelial dysfunction and apoptosis of the trophoblast cells, but also involves telocytes and its putative role in the regulation of fetal blood flow and the intra-placental blood volume. Some ideas aimed at dilucidating the relationship between placental failure and the behavior of telocytes in pathological organs in adulthood, are also discussed., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aim: To assess the impact that pregestational insulin resistance (PIR) has as a risk factor for preeclampsia (PE)., Methods: Nested case-control study that included patients with PIR and a control group that was randomly selected from pregnancies admitted to the Fetal Medicine Unit between January 2005 and May 2011. Clinical and hemodynamic variables were analyzed by a multiple logistic regression analysis., Results: Of the 13,124 patients admitted during the study period, 119 had a diagnosis of PIR (0.9%). Patients with PIR were older and had a higher body mass index (BMI). PIR was also related to a significantly higher frequency of chronic hypertension (CrHT; 10.1 vs. 2.2%, p < 0.05) and hypothyroidism (5.0 vs. 1.6%, p < 0.05) than in the control group. Moreover, women with PIR were more likely to develop PE (8.4 vs. 4.2%, p < 0.05) and gestational diabetes mellitus (9.2 vs. 2.9%) than the control group. Multivariate analysis showed that maternal age, CrHT and altered uterine artery Doppler sonography during the first and second trimesters were good predictors of PE and that PIR was not., Conclusion: Although PIR correlates with PE, conditions related to the latter (CrHT, higher maternal age and increased BMI) may be predominant as risk factors for PE., (© 2014 S. Karger AG, Basel.)

Objective: To determine whether oral glucose tolerance tests (OGTT) play a role as predictors of preeclampsia (PET) in pregnant women., Methods: A retrospective case-control study was conducted in 2,002 singleton pregnancies that had a uterine artery (UtA) Doppler at 22-25 weeks and an OGTT. The UtA Doppler and OGTT were adjusted based on maternal characteristics, and the results were expressed as multiples of the expected normal median and compared between groups. Logistic regression analysis was used to determine whether maternal characteristics, OGTT, and UtA Doppler significantly contribute to the prediction of early- (<34 weeks), intermediate- (34-37 weeks), or late-onset (>37 weeks) PET. The performance of the screening was determined by ROC curves., Results: Women who developed PET were characterized by an older maternal age, an increased body mass index, and an altered UtA Doppler. The group with intermediate-onset PET was the only one associated with higher 2-hour OGTT levels compared to controls. Combined models were developed via logistic regression analysis using maternal characteristics, UtA Doppler, and OGTT to predict PET. These combined models were able to detect around 74, 42, and 21% of women who later developed early-, intermediate-, or late-onset PET, respectively, with only a 5% false-positive rate., Conclusions: This study shows that the combination of maternal characteristics, second-trimester UtA Doppler, and OGTT is a predictor of the development of PET in healthy pregnant women., (© 2014 S. Karger AG, Basel.)

Objective: To develop a predictive model for pre-eclampsia using clinical, biochemical and ultrasound markers during the first trimester of pregnancy., Methods: This was a nested case-control study within a pre-eclampsia screening project that involved 5367 asymptomatic pregnant women undergoing routine transvaginal uterine artery (UtA) Doppler at 11 + 0 to 13 + 6 weeks. Following exclusions, there were 70 pregnant women who later developed pre-eclampsia and 289 control patients enrolled during the first trimester who had serum or plasma samples taken at enrolment available for the purposes of this study. Of these, 17 pregnancies were diagnosed with early-onset (delivery < 34 weeks) pre-eclampsia and 53 with late-onset (delivery ≥ 34 weeks) pre-eclampsia. The lowest, highest and mean of left and right UtA pulsatility indices (PI) were calculated. Blood samples were stored at -84 °C until biochemical analysis for markers of vasculogenesis was performed. The distributions of the lowest UtA-PI and the biochemical markers were adjusted for maternal characteristics, expressed as multiples of the median (MoM), and compared between groups. Logistic regression analysis was used to evaluate if any variable was significantly associated with pre-eclampsia., Results: Pregnancies that later developed pre-eclampsia were associated with higher maternal prepregnancy body mass index. An increased lowest UtA-PI was significantly associated with both early- and late-onset disease. Placental growth factor (PlGF) MoM was significantly reduced in women who later developed early- or late-onset pre-eclampsia compared with controls (median (interquartile range), 0.69 (0.33-1.46) and 1.10 (0.39-1.56), respectively, vs 1.19 (0.65-1.84), P < 0.05). Different combined models were generated by logistic regression analysis, and the detection rate with a fixed 10% false-positive rate was 47% and 29% for early- and late-onset pre-eclampsia, respectively., Conclusion: Pregnancies that later developed early or late pre-eclampsia were characterized by impaired placentation and an anti-angiogenic state during the first trimester of pregnancy. Regression models which include maternal characteristics, UtA Doppler and PlGF can apparently predict approximately half of pregnancies that will be complicated by early-onset pre-eclampsia. We believe more research in several areas is needed to aid in the creation of a better and more population-specific screening test for pre-eclampsia during the first trimester of pregnancy., (Copyright © 2012 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To determine the relationship of biomarkers of placental damage by oxidative stress in pre-eclamptic placenta., Methods: A case-control study was performed on a population of 14 pregnant women with PE and 12 women with normal pregnancies. Immunohistochemical expressions of VEGF, vWF distribution, (Na + K)-ATPase activity, and abundance of nitrotyrosine residues, were assessed in the placental tissue., Results: Women with pre-eclampsia showed increased VEGF expression and abundance of nitrotyrosine residues in placental villous, and plasma vWF levels (p < 0.05), whereas placental (Na + K)-ATPase activity were significantly reduced. The syncytiotrophoblast and the maternal space of pre-eclamptic placenta showed diminished and increased vWF expression, respectively, but no significant differences in its expression were found in the placental endothelium and stroma (p < 0.05)., Conclusions: It could be suggested that increased oxidative stress and VEGF contribute to enhance the impairment of placental perfusion by increasing peroxynitrite formation, product of the NO and superoxide reaction, thereby partly contributing to account for the pathophysiology of this disease. The presence of vWF in the maternal space and its diminished expression in syncytiotrophoblast of pre-eclamptic placenta also might have pathogenic implications.

Preeclampsia is a high-prevalence systemic pregnancy disorder associated with maternal and foetal mortality. Its pathogenesis is unknown, but it is thought that oxidative stress and endothelial dysfunction may play a fundamental role. Von Willebrand factor (vWF), a marker of endothelial cell injury, can be found in different cells and zones of the placenta. To determine the differential immunoexpression of vWF at different tissue types of preeclamptic placenta and endothelial dysfunction markers at maternal serum of preeclamptic pregnancies. A case-control study was performed on a population of pregnant women with preeclampsia (n = 14), and normal pregnancies (n = 8). Placental and blood plasma samples were withdrawn at delivery. Immunohistochemical vWF expression in the placental tissue was determined. Endothelial dysfunction was assessed through plasminogen activator inhibitor (PAI) 1 and 2 ratio and vWF concentration in maternal plasma. P values less than 0.05 were considered statistically significant. Preeclamptic women showed increased plasma PAI-1/PAI-2 ratio (P < 0.05). There was diminished placental vWF expression in syncytiotrophoblast and increased in the intervillous space of preeclamptic placentas (P < 0.05). No significant differences in vWF expression were found in the villous endothelium and stroma, but it was significantly higher in maternal plasma (P < 0.05). In preeclampsia occurs endothelial damage and placental cell injury. Cell damage in syncytiotrophoblast that occurs in preeclampsia could liberate vWF from syncytiotrophoblast to the placental intervillous space, and this may have pathogenic implications.

The pathophysiology of preeclampsia (PE), a disorder occurring in 5% of all pregnancies, remains largely unknown, but early placental hypoxia and oxidative stress are known to be involved in the mechanism of the syndrome. Maternal plasma and placental tissue samples were collected from PE, intrauterine growth restriction (IUGR), and normotensive pregnant patients. The immunohistochemical expression of vascular endothelial growth factor (VEGF), malondialdehyde (MDA) production and the activity of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase GSH-Px) were determined in the placental tissue. F2-isoprostane concentration and the ferric reducing ability of plasma (FRAP) were determined in maternal plasma. We found that the PE and IUGR groups showed a higher expression of VEGF in the muscular layer of fetal chorionic vessels. In addition, increased plasma F2 isoprostane levels and a significant reduction of FRAP in the plasma of PE women, as well as a lower activity of SOD in PE placentas and a higher activity of GSH-Px in IUGR placentas were found. Additionally, lower PlGF and higher sFlt1 levels were observed in the maternal plasma of PE and IUGR than control. We concluded that in a hypoxic environment, the placenta expresses VEGF in the muscular layer of fetal vessels. The development of PE could be related to the increased expression of VEGF, with decreased placental SOD activity and a decrease of both plasma F2-isoprostane and FRAP levels. In turn, the development of IUGR could be related to the association of decreased plasma FRAP levels and increased placental GSH-Px activity.

Objectives: We sought to examine whether the maternal serum concentration of soluble vascular cell adhesion molecule 1 (sVCAM-1) and intercellular adhesion molecule 1 (sICAM-1) at 11+0-13+6 weeks of gestation could improve the prediction for subsequent development of pre-eclampsia., Methods: A nested case-control prospective study of pregnancies having uterine artery Doppler routinely at 11+0-13+6 weeks of gestation was conducted to determine the maternal serum concentration of sICAM-1 and sVCAM-1 in peripheral blood samples obtained from 18 women who later developed pre-eclampsia and 60 unaffected women., Results: The mean uterine artery pulsatility index was higher (2.2 +/- 0.6 vs. 1.8 +/- 0.5, p < 0.05) in the pre-eclampsia compared with the unaffected pregnancies. There were no significant differences between the groups in the mean serum concentration of either adhesion molecule., Conclusions: These results suggest that there is no endothelial activation before the appearance of clinical signs of pre-eclampsia. Therefore, these biochemical markers are unlikely to become early predictors of this condition.