Signs Of Preeclampsia Research Articles

Spontaneous liver rupture in a pregnant woman associated with HELLP syndrome

Spontaneous liver rupture is rare and highly dangerous, life-threatening condition occurring in 1–2% of pregnant women with preeclampsia and eclampsia. There are more than 100 similar case reports in the literature. It is believed that liver rupture is caused by HELLP syndrome as one of the signs of preeclampsia. The results of surgical treatment is still unsatisfactory. Appropriate treatment strategy is absent because of rareness of this condition. It is presented case report of a woman with spontaneous liver rupture associated with HELLP syndrome. Patient underwent perihepatic tamponade, endovascular embolization of right hepatic artery followed by right-sided hemihepatectomy.

Characterisation of the Selective Reduced Uteroplacental Perfusion (sRUPP) Model of Preeclampsia

Preeclampsia is a complication of pregnancy characterised by gestational hypertension, proteinuria and/or end organ disease. The reduced uteroplacental perfusion (RUPP) model, via partial occlusion of the lower abdominal aorta, mimics insufficient placental perfusion as a primary causal characteristic of preeclampsia. However, a major limitation of the RUPP model is that perfusion is reduced to the entire hindquarters of the rat resulting in hindlimb ischemia. We hypothesised that clipping the uterine and ovarian arteries in the selective (s)RUPP model would provoke signs of preeclampsia while avoiding systemic ischemia. Sham, RUPP or sRUPP procedures were performed in pregnant Sprague Dawley rats on gestational day (GD)14. On GD21 uterine blood flow was significantly reduced in both the RUPP and sRUPP models while aortic flow was reduced only in RUPP. Both models resulted in increased MAP, increased vascular oxidative stress (superoxide generation), increased pro-inflammatory (RANTES) and reduced pro-angiogenic (endoglin) mediators. Vascular compliance and constriction were unaltered in either RUPP or sRUPP groups. In summary, refinements to the RUPP model simultaneously maintain the characteristic phenotype of preeclampsia and avoid peripheral ischemia; providing a useful tool which may be used to increase our knowledge and bring us closer to a solution for women affected by preeclampsia.

The Role of Anticoagulant Therapy in the Prevention of Preeclampsia Pharmacokinetic and pharmacodynamic mechanisms

Pregnancies complicated with preeclampsia associate a high incidence of intrauterine fetal death, intrauterine growth restriction, premature ruptures of membranes, abruption placentae and prematurity. Understanding the pathogenesis of preeclampsia is mandatory for a correct approach and prevention management of high risk cases. Placental hypoperfusion seems to be a key factor in developing systemic resounding. By placental necrosis and apoptosis, cell-free DNA is released in maternal circulation in early pregnancy, respectively prior 17 weeks of gestation. There is no test, useful in early pregnancy, accurate enough to predict preeclampsia. Various screening test have been proposed in order to predict the development of preeclampsia, but most of them are not sufficiently accurate for general screening. There is a continuous debate regarding the algorithm of administration, doses and timing of low dose aspirin. The initiation moment is crucial, as the administration after the development symptoms and signs of preeclampsia do not interfere with the progression and the severity of the disease. Early initiation of therapy with low dose aspirin, prior the end of the first trimester is important since the pathogenesis mechanisms of preeclampsia take place in the first trimester. The action of acetylsalicylic acid consists in inhibition of COX-1 and COX-2 (cyclooxygenase isoenzymes), necessary for prostaglandin biosynthesis. Preferential inhibition of Thromboxane A2 by low dose aspirin, counterbalance the increased production of thromboxanes characteristic to preeclampsia and modulate the inflammatory process, amplified in pregnant women with preeclampsia.

Preeclampsia and Cerebrovascular Disease.

Preeclampsia and Cerebrovascular Disease.

Liver enzyme patterns in maternal deaths due to eclampsia: A South African cohort

Eclampsia is an obstetric emergency and a major cause of maternal mortality in low and middle-income countries such as South Africa. Despite years of research, there is no single test for the prediction of eclampsia, however liver function tests have been effective in monitoring the prognosis of this disorder. This was a retrospective study of patients in whom the final cause of death was eclampsia in South Africa between the years 2014-2016. Of 109 cases who died from eclampsia, the highest prevalence was found among primigravidae (42.1%: n = 45) of whom 26.6% (n = 29) were between 20 and 24 years of age. Twenty-six (23.9%) eclamptics did not receive antenatal care and of these 80.7% (n = 21) had the first eclamptic seizure at home. The first level of health care was used by 63.3% (n = 69) of patients; liver function test results were documented in 56.9% (n = 57). An association was found between eclampsia and elevated aspartate aminotransferase levels. Primigravidae especially teenagers are at risk of eclampsia. These women in particular must be informed of the warning signs of preeclampsia and requested to attend for antenatal care frequently especially in the third trimester so that early signs of preeclampsia are detected and timeous delivery is carried out to prevent eclampsia. Furthermore, liver function tests and platelet counts should be done in all women with the preeclampsia-eclampsia syndrome during antenatal and in the immediate postpartum period to prognosticate progression of the disorder and or timing of discharge from hospital.

Accuracy of Second Trimester Prediction of Preterm Preeclampsia by 3 Different Screening Algorithms

(Aust N Z J Obstet Gynaecol. 2018;58:192–196) Preeclampsia (PE) is a major risk factor for maternal and perinatal morbidity and mortality. Thus, early screening in the first trimester to identify patients at high risk for PE allows the initiation of early preventive measures, such as low-dose aspirin therapy begun before 16 weeks gestation. Many women, though, do not have their first prenatal visit until after 16 weeks, and identifying high-risk patients in the second trimester can still be beneficial, especially for identifying early signs of PE and providing timely treatment. Currently, the National Institute for Health and Clinical Excellence (NICE) in the United Kingdom has guidelines for identifying at risk women using maternal demographics and medical history. Likewise in the United States, the American College of Obstetricians and Gynecologists (ACOG) have recommendations for screening that uses demographics and medical history to define those women considered at high risk for PE. In contrast, the Fetal Medicine Foundation (FMF) has published an algorithm for identifying women at risk for early PE that includes measurement of mean arterial pressure and uterine artery Doppler pulsatility index in addition to medical history. This prospective nonintervention study aimed to compare the efficacy of these three screening methods used during the second trimester to predict the occurrence of PE.

Using a smartphone app to identify signs of pre-eclampsia and/or worsening blood pressure

Background Hypertensive disorders of pregnancy complicate 10% of pregnancies and can have serious consequences. Aims To explore the experiences of pregnant women with a history of hypertension using an innovative home blood pressure monitoring device. Methods A qualitative study using a grounded theory approach was undertaken. Data were collected through semi-structured interviews. Women were given a blood pressure machine to monitor their blood pressure daily. They inserted their blood pressure results on a smartphone app and answered questions for signs of pre-eclampsia. Participants were followed up every 2 weeks. Findings The results suggested that women wanted a holistic care pathway for the management of hypertension in pregnancy. Three subcategories (‘empowerment’, ‘comparison of care pathways’ and ‘continuity of care’) were also identified. Conclusions The traditional management of hypertension in pregnancy is not holistic. The home blood pressure service was accepted by women and incorporated elements of holistic care but more is required to meet the standard of care that women need.

In-situ gel of nifedipine for preeclampsia: Optimization, in-vitro and in-vivo evaluation

Present study was conducted to develop and optimize in-situ gel for sustained delivery of Nifedipine by ion sensitive mechanism and its in-vitro and in-vivo evaluation. Factorial design was employed to evaluate the effect of gellan gum and HPMC K4M on drug release and viscosity. Optimized formulation showed 55.12% drug release at 6 h with viscosity of 195.66cps and followed diffusion controlled release mechanism. In-vivo gastroretentive ability was monitored by gamma camera which confirmed that gel remain in human stomach for more than 8 h. Preeclampsia was induced by intra-peritoneal injection of L-NAME for 7 days in pregnant mice which showed that L-NAME mimics the classical signs of preeclampsia and in-situ gel reduced proteinuria from >1000 mg/dL to 300 mg/dL and improved the foetal litter number from 6.2 ± 2.3 for preeclampsia induced group to 9.1 ± 1.2 for treated group. Pharmacokinetic studies showed Cmax, Tmax, MRT and AUC values of optimized formulation to be 512.33 ± 77.81 ng/ml, 6.00 ± 0.29 h, 8.55 ± 1.36 h and 4358.24 ± 157.90 ng h/ml respectively with relative bioavailability of 1.24. Thus, it can be concluded that floating in-situ gel can be an alternative approach for routine hypertension management in preeclampsia patients.

Inhaled carbon monoxide increases vasodilation in the microvascular circulation

Preeclampsia (PE) is characterized by systemic maternal endothelial dysfunction. Changes in endothelial reactivity have been reported before the onset of clinical signs of PE, and continuing into the post-partum period. Women who smoke during pregnancy have a 33% reduced risk of developing PE. This reduced risk is hypothesized to be, in part, attributed to carbon monoxide (CO), a by-product of cigarette combustion and a known endogenous vasodilator. Determining the vascular effects of CO in healthy women, may inform how CO can improve endothelial function and have promise as a novel therapeutic for PE. As part of a pilot study to determine the vascular effects of CO, the aim of this study was to measure microvascular vasodilation following low-dose CO inhalation. Non-pregnant women inhaled ambient room air or 250 ppm CO for 24 min during microvascular assessment using laser speckle contrast imaging. Changes in vascular flux were measured in the forearm before, during, and following a three-minute arterial occlusion. CO inhalation increased end-tidal breath CO (EtCO) (9.1 ± 1.9 vs. 1.8 ± 0.7 ppm, p < 0.05) and increased microvascular vasodilation, measured as difference of maximum level/resting level ratio (mean difference 0.476, 95% confidence interval (CI) = 0.149–0.802 vs. 0.118, 95% CI = −0.425–0.662, p < 0.05). Women who inhaled CO had a longer time to half recovery of endothelial function following arterial occlusion, compared to controls (hazard ratio 0.29, 95% CI = 0.10–0.91, p = 0.033). Inhalation of CO moderately increased EtCO and resulted in an increased microvascular response, suggesting that CO may have potential as a therapeutic for PE.

The Association Between Resistivity Index (IR) and the sFlt-1 and PIGF Values in Pregnant Women With Risk of Preeclampsia

Worldwide, 5-8% of pregnant women are diagnosed with preeclampsia. This disease increases the morbidity and mortality of the fetus and pregnant woman, especially in developing countries. Preeclampsia is characterized by systolic blood pressure ] 140mmHg or diastolic blood pressure] 90mmHg as measured twice, and 24 h proteinuria �0.3 g, after 20 weeks of gestation. The cause of preeclampsia is still incompletely elucidated. Numerous studies have suggested to modernize the definition of preeclampsia by incorporating key biomarkers of either placental or vascular origins, including placental growth factor (PIGF) and antiangiogenic factors such as tyrosine kinase-1 (sFlt-1) in the diagnosis of preeclampsia and the risk of occurrence of the disease in the second trimester of pregnancy [1-5]. We studied a group of 50 patients with a 21-week pregnancy diagnosis, we calculated the ratio between sFlt-1 and PIGF and we tested to see if there was an association between this ratio and the resistivity index (IR) of the uterine artery using the artery Doppler ultrasound. The PIGF level in our group was decreased in women who developed preeclampsia compared to the control group where this problem did not occur. Doppler ultrasound examination during the second trimester of pregnancy may provide extra data for prediction of preeclampsia. Although much of pathophysiology of preeclampsia has been explained, the exact etiology of this disorder remains unclear. It is certain that before the clinical signs of preeclampsia are detectable, there is an imbalance between pro-angiogenic and anti-angiogenic factors.

Pregnancy Specific Beta-1 Glycoprotein, Pro- and Anti-inflammatory Cytokines in Eclampsia in Kaduna State, Nigeria

Eclampsia (EC), a human pregnancy–specific-syndrome is the life-threatening occurrence of convulsion (s) in association with signs of preeclampsia (hypertension and proteinura). Eclampsia has remained a significant public health threat, contributing to maternal and prerinatal morbidity and mortality in Nigeria. However, the pathogenic mechanism of the disease is not fully understood. Disturbance of the cytokine equilibrium has been accused for many pathological disorders including EC. Thus the aim of this study was to analyze the maternal cytokines and pregnancy specific beta-1 glycoprotein in EC and compared results with those of normal healthy pregnant controls. Enzyme linkedimmunosorbent assay (ELISA) was used to measure levels ofpro-inflammatory cytokines (Tumor necrosis [TNF]-α, and interleukin [IL] -2), anti-inflammatory cytokines [IL-4 and IL-10] and pregnancy specific beta-1 glycoprotein (PSG-1) in the peripheral blood of patients with EC (n=38), normal healthy pregnant women [PC] (n=25) and compared withhealthy non pregnant women controls [NPC] (n=25). Women with malaria and human immunodeficiency virus infections were excluded from the study. The overall results (Mean ±SD) were: TNF-α (2.34 ±0.13 pg/ml) in EC was significantly higher than the mean values (2.25±0.07pg/ml and 2.24±0.10 pg/ml) in PC and NPC respectively. Furthermore, EC had higher TNF-α mean value compared with NPC (P<0.05). There was no statistical difference in mean IL-2 value between EC (1.69±0.17 Pg/ml), PC (1.71±0.0.09Pg/ml) and NPC (1.72±0.13Pg/ml) (P>0.05). The mean value of IL-10 was noted to be lower in EC (1.28±0.54Pg/ml) compared with: PC (1.58±0.61 Pg/ml) and NPC (2.06±0.08Pg/ml). No significant difference in IL-4 mean value exist between EC (2.45±0.10 Pg/ml) and NPC (2.45 Pg/ml) (P>0.05) but significant difference exist between EC and NPC (2.40±0.0 6Pg/ml) (P<0.05). The serum PSG-1 levels in EC (2.5±0.11 Pg/ml) and PC (2.5±0.03 Pg/ml) were similar and significantly higher than in NPC (0.06±0.020 Pg/ml) P<0.05. While a pro-inflammatory cytokine environment was demonstrated in EC, and decreased anti-inflammatory reactivity, EC was not associated with low levels of PSG-1. Further research is advocated to discover how anti-inflammatory cytokines could be exploited as a therapeutic agent for women at high risk of EC.

RNAi modulation of placental sFLT1 for the treatment of preeclampsia.

Preeclampsia (PE) is a placentally-induced hypertensive disorder of pregnancy that is associated with significant morbidity and mortality to mothers and fetuses. Clinical manifestations of preterm PE result from excess circulating soluble vascular endothelial growth factor receptor FLT1 (sFLT1 or sVEGFR1) of placental origin. Here we identify short interfering RNAs (siRNAs) that selectively silence the three sFLT1 mRNA isoforms primarily responsible for placental overexpression of sFLT1. Full chemical stabilization in the context of hydrophobic modifications enables productive siRNA accumulation in the placenta (up to 7% of injected dose) and reduces circulating sFLT1 in pregnant mice (up to 50%). In a baboon PE model, single dose of siRNAs suppressed sFLT1 overexpression and clinical signs of PE. Our results demonstrate RNAi-based extra-hepatic modulation of gene expression with non-formulated siRNAs in non-human primates and establish a path toward a new treatment paradigm for patients with preterm PE.

Arginine vasopressin infusion is sufficient to model clinical features of preeclampsia in mice.

Copeptin, a marker of arginine vasopressin (AVP) secretion, is elevated throughout human pregnancies complicated by preeclampsia (PE), and AVP infusion throughout gestation is sufficient to induce the major phenotypes of PE in mice. Thus, we hypothesized a role for AVP in the pathogenesis of PE. AVP infusion into pregnant C57BL/6J mice resulted in hypertension, renal glomerular endotheliosis, intrauterine growth restriction, decreased placental growth factor (PGF), altered placental morphology, placental oxidative stress, and placental gene expression consistent with human PE. Interestingly, these changes occurred despite a lack of placental hypoxia or elevations in placental fms-like tyrosine kinase-1 (FLT1). Coinfusion of AVP receptor antagonists and time-restricted infusion of AVP uncovered a mid-gestational role for the AVPR1A receptor in the observed renal pathologies, versus mid- and late-gestational roles for the AVPR2 receptor in the blood pressure and fetal phenotypes. These findings demonstrate that AVP is sufficient to initiate phenotypes of PE in the absence of placental hypoxia, and indicate that AVP may mechanistically (independently, and possibly synergistically with hypoxia) contribute to the development of clinical signs of PE in specific subtypes of human PE. Additionally, they identify divergent and gestational time-specific signaling mechanisms that mediate the development of PE phenotypes in response to AVP.

425. How does programming work – Animal models of placental dysfunction and their epigenetic outcome

An adverse intrauterine environment belongs to the well-known roots of chronic disease in adult life. This is often coined the ’Developmental Origins of Health and Disease’ (DOHaD) paradigm. One of the key factors transmitting environmental information along the lifespan of an organism is epigenetic programming. Classical rodent models used in research on the Developmental Origins of Health and Disease are based on dietary interventions during pregnancy. Simulation of human hunger periods by caloric or protein restriction are examples. Similarly, placental dysfunction is often simulated by clamping of the uterine artery, which requires surgical procedures. I will here compare several novel mouse models of placental dysfunction and their benefits for research. These models are based on the genetic deletion of the transcription factor TFAP2C in the placenta, or on a combination of virus-mediated overexpression of sFlt1, with or without low-grade inflammation. The former model leads to growth restriction in the offspring, whereas the latter model is furthermore accompanied by signs of preeclampsia. Interestingly, in both cases also the sex of the offspring matters for the outcome. These new models, especially when compared to each other, will in future allow us to specifically differentiate between different forms of placental dysfunction, which might contribute to personalized care strategies.

35. Early- and late-onset of pre-eclampsia: How do the maternal circulating biomarkers differ, and why?

Pre-eclampsia requires the presence of placenta or residual placental compounds (as in postpartum pre-eclampsia), but the relative contribution of maternal predisposing factors versus placental factors to its pathophysiology is not well understood. The talk will revisit the classical “two-stage model” of pre-eclampsia, as proposed by Redman et al. in 1999, where incomplete placentation is the first of two stages of pre-eclampsia, typically of early onset. Maternal “intolerance” of fetal cells and failed uteroplacental spiral artery remodelling has been a proposed pathway for poor placentation, which however involves several mechanisms. The second stage comprises dysfunctional uteroplacental perfusion and placental oxidative stress, followed by secretion of inflammatory factors to the maternal circulation, with ensuing generalized maternal vascular inflammation and pre-eclampsia signs (maternal hypertension and proteinuria). We have suggested (Redman, Sargent and Staff, Placenta 2013) that the mechanisms leading to a dysfunctional uteroplacental circulation may involve additional mechanisms to poor placentation, and that syncytiotrophoblast (STB) stress, with upregulation of some proteins (as exemplified by “antioangiogenic proteins”) and downregulation of others (exemplified by “proangiogenic proteins”) is the common final pathway. We argue that maternal circulating angiogenic factors are markers of STB stress, not of preeclampsiaper se. We have proposed two major forms of placental dysfunction in pre-eclampsia: one extrinsic (poor placentation) and one intrinsic cause (villous overcrowding). Our model explains important differences of early- and late-onset pre-eclampsia, including their relation to maternal circulating placenta-associated proteins used as biomarkers for the syndrome (Redman and Staff, AJOG 2015). The talk will also argue that there is no condition such as “maternal” pre-eclampsia, as all pre-eclampsia originate in the placenta. We suggest however that maternal factors may contribute two both stages of pre-eclampsia, the first by affecting either placental pathways to STB stress and the latter by amplifying the effects of STB stress on maternal vasculature.

Abstract P313: Isolated Central Hypertension and Features of the Pregnancy Courseisolated Central Hypertension and Features of the Pregnancy Course

Background: Physiological features of hemodynamic changes in pregnant Women seem to be important for the implementation of personalized prevention and effective prediction of the upcoming vascular events of Women itself and its offspring too. The problem of hypertension in pregnant women (PW) is a subject of many studies. However, to question of isolated increasing of aortic pressure during pregnancy was given much less attention. We aimed to evaluate the indices of vascular stiffness in pregnant women in the presence of isolated central hypertension (ICH) in correlation with some complications of pregnancy. Methods: The study included 89 women in the first trimester of pregnancy. Evaluated the signs of pre-eclampsia (PE) and syndrome of delayed fetal growth (SDFG). Determining of central pressure (CP) was performed using diagnostic system BPLab (Petr Telegin, Russia) on software Vasotens Office. Inclusion criteria - level of systolic pressure on shoulder in the range of 110-129 mm Hg. Among these women were identified bearers of CP on the level above 90th percentile for the relevant age group in accordance with established reference indicators by Herbert A. e.a. (2014). These women were included in first group with ICH (27 persons). The rest ones with normal pressure on shoulder and in the aorta constituted the second control group (62 persons). The groups did not differ by age. Data were processed using software package "Statistica 10.0" (StatSoft Inc, USA). Results: It turned out that carriers of ICH had higher parameters of vascular stiffness compared with women in the control group. Particularly significant difference is revealed from the side of the aortic augmentation index - 5,4±1,1 vs 2,1±0,8. All cases of complications of pregnancy were identified only in the first group. So the frequency of PE and SDFG amounted to 11,1%.The average weight of newborns of the first group also differed from the control in direction of its decrease - 3338±99,6g vs 3487±125,3g. Conclusions: The presented results reflect the approach to the formation of new and more effective system of health care of pregnant women that is focused on predictive diagnostics of personalized threat profile for implementation targeted preventive measures in subsequent.

Proteinuria in preeclampsia: is it important?

Our aim is to evaluate the laboratory results and proteinuria levels of preeclamptic women and their relation-ships to maternal and fetal outcomes. One hundred preeclamptic pregnant women who gave birth in our clinic between 2013 and 2015 were included in our study retrospectively. The data collected from the patients included gestational week, age, gravidity, parity, abortus history, blood pressure, biochemical parameters, delivery method, maternal hospitalization time, cesarean indication, complications, blood products required, plasmapheresis use and dialysis need. The details about the newborns were recorded retrospectively. The relationships between preeclampsia signs and maternal and neonatal out-comes were analyzed. The protein amounts were analyzed via 24-hour collected urine analyses and spot urine analyses. A statistically significant positive correlation was observed between neonatal intensive care unit needs and pro-teinuria levels. Fetal growth restriction, respiratory distress syndrome and sepsis were observed as the level of proteinuria increased, but the result was not statistically significant. Eclampsia was observed only in patients with massive proteinuria, and it was statistically significant. An increase in cesarean sections, placental abruptions, antihypertensive drug needs and blood product replacement rates was observed as the amount of proteinuria increased in preeclamptic women, but the results were not statistically significant. The severity of preeclampsia cannot be determined by the level of proteinuria. However, when massive proteinuria is detected, the clinician should be more cautious about maternal and fetal complications.

Neurofilament as Neuronal Injury Blood Marker in Preeclampsia.

Preeclampsia has been shown to be associated with changes in cerebral structure and cognitive function later in life. Nf (neurofilaments) are specific scaffolding proteins of neurons, and their quantification in serum has been proposed as a biomarker for neuroaxonal injury. We performed a prospective, longitudinal, single-center study at the University Hospital of Basel to determine serum Nf concentrations in pregnant women with singleton pregnancies and with high risk of preeclampsia or with early signs of preeclampsia. Enrollment started at 21 weeks of gestation, followed up with multiple visits until delivery. Sixty out of 197 women developed preeclampsia (30.5%). NfL (Nf light chain) was measured with a highly sensitive single molecule array (Simoa) assay, in addition to the established preeclampsia markers sFlt-1 (soluble fms-like tyrosine kinase-1) and PlGF (placental growth factor). The most important independent predictors of NfL were maternal age, number of pregnancies, and proteinuria. NfL levels increased during pregnancy and were significantly higher in women developing preeclampsia. The discriminatory accuracy of NfL, PlGF, and sFlt-1 in receiver operating characteristic curves analysis (area under the curve) of the overall group was 0.68, 0.81, and 0.84, respectively, and in women older than 36 years 0.7, 0.62, and 0.79, respectively. We conclude that increased axonal injury serum marker NfL predicts preeclampsia particularly in older women, with an accuracy similar to the established angiogenic factors. NfL may serve as an early indicator of preeclampsia-induced changes in cerebral structure and may help to stratify disease management.

Arterial stiffness but not physical activity levels and vascular endothelial function are altered in early/mid pregnancy in women who develop preeclampsia

Preeclampsia is a pregnancy disorder that effects ~5–8% of all pregnancies and is characterized by de novo hypertension, proteinuria and multiple organ dysfunction in late gestation. Higher levels of leisure time physical activity (LTPA) are associated with lower risk of preterm delivery and preeclampsia in pregnancy. Women who develop preeclampsia demonstrate increased central artery stiffness and vascular endothelial dysfunction in early/mid gestation before clinical signs/symptoms of preeclampsia manifest. Therefore, we hypothesized that 1) higher total LTPA would be associated with lower arterial stiffness and higher vascular endothelial function during each trimester in pregnant women, and 2) compared with normal pregnancy, women who develop preeclampsia would demonstrate lower LTPA, higher arterial stiffness and lower endothelial function in early/mid gestation before signs of preeclampsia manifest. We enrolled 130 pregnant women in the first trimester (age 29.8 ± 0.4 yrs; BMI 28 ± 0.7 kg/m2) and studied them prospectively in the 1st (n=130; 11.8 ± 0.1 weeks gestation), 2nd (n=97; 22 ± 0.2 weeks) and 3rd (n=59; 34.2 ± 0.3 weeks) trimesters and obtained pregnancy outcomes (i.e., developed preeclampsia vs. normal pregnancy). Total LTPA (Pregnancy Physical Activity Questionnaire) in metabolic equivalents (MET‐hrs/week), carotid artery β‐stiffness (carotid ultrasound and tonometry), aortic stiffness (carotid‐femoral pulse wave velocity, CFPWV) and endothelial function (brachial artery flow‐mediated dilation, FMD) were assessed each trimester. In the entire cohort, there was no association between total LTPA and carotid β‐stiffness, CFPWV, FMD or BP in 1st (all P&gt;0.05), 2nd (all P&gt;0.05) or 3rd (all P&gt;0.05) trimesters, respectively. Out of the 104 women who delivered, 9 (8.7%) developed preeclampsia. Because 6 women in the preeclampsia group delivered prematurely, only 1st and 2nd trimester comparisons were made between the preeclampsia and normal pregnancy groups. There was no difference in LTPA between preeclampsia and normal pregnancy in the 1st (204 ± 31 vs. 182 ± 7 MET‐hrs/wk, P=0.41) and 2nd (145 ± 30 vs. 175 ± 8 MET‐hrs/wk, P=0.33) trimesters. In contrast, CFPWV and systolic BP were elevated in the 1st (5.9 ± 0.4 vs. 5.2 ± 0.1 m/sec, P=0.03; 121 ± 5 vs. 109 ± 0.9 mmHg P&lt;0.01) and 2nd (5.8 ± 0.6 vs. 4.9 ± 0.1m/sec, P&lt;0.01; 126 ± 5 vs. 106 ± 0.9 mmHg, P&lt;0.01) trimesters in preeclampsia and normal pregnancy, but carotid β‐stiffness was only elevated in the 1st trimester (7.42 ± 1.4 vs. 5.96 ± 0.17 U, P=0.05). Brachial artery FMD was not different between groups in 1st or 2nd trimester (both P&gt;0.05). These preliminary data suggest that LTPA is not associated with arterial stiffness or endothelial function throughout pregnancy and that LTPA is not lower in early/mid gestation in women who develop preeclampsia. Central artery stiffness and BP are elevated early in pregnancy in women who develop preeclampsia months before clinical signs/symptoms manifest.Support or Funding InformationAmerican Heart Association (15SFRN23730000; 17POST334410101), American Physiology Society STRIDE undergraduate summer research fellowship; National Institutes of Health (T32HL007121).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Resting-state functional connectivity in children born from gestations complicated by preeclampsia: A pilot study cohort.

Individuals (PE-F1s) born from preeclampsia (PE)-complicated pregnancies have elevated risks for cognitive impairment. Intervals of disturbed maternal plasma angiokines precede clinical signs of PE. We hypothesized pan-blastocyst dysregulation of angiokines underlies altered PE-F1 brain vascular and neurological development. This could alter brain functional connectivity (FC) patterns at rest. Resting-state functional MRI datasets of ten, matched child pairs (5 boys and 5 girls aged 7-10 years of age) from PE or control pregnancies were available for study. Seed-based analysis and independent component analysis (ICA) methodologies were used to assess whether differences in resting-state functional connectivity (rs-FC) were present between PE-F1s and controls. Bilateral amygdala, bilateral hippocampus, and medial prefrontal cortex (MPFC) were selected as regions of interest (ROI) for the seed-based analysis based on previous imaging differences that we reported in this set of children. Compared to controls, PE-F1 children had increased rs-FC between the right amygdala and left frontal pole, the left amygdala and bilateral frontal pole, and the MPFC and precuneus. PE-F1 children additionally had decreased rs-FC between the MPFC and the left occipital fusiform gyrus compared to controls. These are the first reported rs-FC data for PE-F1s of any age. Theysuggest that PE alters FC during human fetal brain development. Altered FC may contribute to the behavioural and neurological alterations reported in PE-F1s. Longitudinal MRI studies with larger sample sizes are required to confirm these novel findings.