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The opinion on the mechanisms underlying the pathogenesis of preeclampsia still divides scientists and clinicians. This common complication of pregnancy has long been viewed as a disorder linked primarily to placental dysfunction, which is caused by abnormal trophoblast invasion, however, evidence from the previous two decades has triggered and supported a major shift in viewing preeclampsia as a condition that is caused by inherent maternal cardiovascular dysfunction, perhaps entirely independent of the placenta. In fact, abnormalities in the arterial and cardiac functions are evident from the early subclinical stages of preeclampsia and even before conception. Moving away from simply observing the peripheral blood pressure changes, studies on the central hemodynamics reveal two different mechanisms of cardiovascular dysfunction thought to be reflective of the early-onset and late-onset phenotypes of preeclampsia. More recent evidence identified that the underlying cardiovascular dysfunction in these phenotypes can be categorized according to the presence of coexisting fetal growth restriction instead of according to the gestational period at onset, the former being far more common at early gestational ages. The purpose of this review is to summarize the hemodynamic research observations for the two phenotypes of preeclampsia. We delineate the physiological hemodynamic changes that occur in normal pregnancy and those that are observed with the pathologic processes associated with preeclampsia. From this, we propose how the two phenotypes of preeclampsia could be managed to mitigate or redress the hemodynamic dysfunction, and we consider the implications for future research based on the current evidence. Maternal hemodynamic modifications throughout pregnancy can be recorded with simple-to-use, noninvasive devices in obstetrical settings, which require only basic training. This review includes a brief overview of the methodologies and techniques used to study hemodynamics and arterial function, specifically the noninvasive techniques that have been utilized in preeclampsia research.

The functional maternal-fetal hemodynamic unit includes fetal umbilical vein flow and maternal peripheral vascular resistance.This study investigated the relationships between maternal and fetal hemodynamics in a population with suspected fetal growth restriction.This was a prospective study of normotensive pregnancies referred to our outpatient clinic for a suspected fetal growth restriction. Maternal hemodynamics measurement was performed, using a noninvasive device (USCOM-1A) and a fetal ultrasound evaluation to assess fetal biometry and velocimetry Doppler parameters. Comparisons among groups were performed with 1-way analysis of variance with Student-Newman-Keuls correction for multiple comparisons and with Kruskal-Wallis test where appropriate. The Spearman rank coefficient was used to assess the correlation between maternal and fetal hemodynamics. Pregnancies were observed until delivery.A total of 182 normotensive pregnancies were included. After the evaluation, 54 fetuses were classified as growth restricted, 42 as small for gestational age, and 86 as adequate for gestational age. The fetus with fetal growth restriction had significantly lower umbilical vein diameter (P.0001), umbilical vein velocity (P=.02), umbilical vein flow (P.0001), and umbilical vein flow corrected for fetal weight (P.01) than adequate-for-gestational-age and small-for-gestational-age fetuses. The maternal hemodynamic profile in fetal growth restriction was characterized by elevated systemic vascular resistance and reduced cardiac output. The umbilical vein diameter was positively correlated to maternal cardiac output (rMaternal and fetal hemodynamic parameters were different in the 3 groups of fetuses: fetal growth restriction, small for gestational age, and adequate for gestational age. Maternal hemodynamic parameters were closely and continuously correlated with fetal hemodynamic features. In particular, a maternal hemodynamic profile with high systemic vascular resistance, low cardiac output, reduced inotropism, and hypodynamic circulation was correlated with a reduced umbilical vein flow and increased umbilical artery pulsatility index. The mother, placenta, and fetus should be considered as a single cardiac-fetal-placental unit. The correlations of systemic vascular resistance, cardiac output, and inotropy index with umbilical artery impedance indicate the key role of these 3 parameters in placental vascular tree development. The umbilical vein flow rate and, therefore, the placental perfusion seems to be influenced not only by these three parameters but also by the maternal cardiovascular kinetic energy.

Objectives To assess and correlate changes in body composition and haemodynamic function during pregnancy. To identify different haemodynamic profiles based on the onset of hypertensive diseases such as gestational hypertension and preeclampsia. Methods We enrolled 265 healthy, normotensive pregnant women throughout pregnancy (from 6 + 0 to 36 + 0 weeks). They were subjected to assessment of body composition and haemodynamic function using non-invasive methods. We divided our population in three groups: group A with physiological pregnancy, group B with gestational hypertension and group C with preeclamptic patients. Results In patients who developed gestational hypertension we found lower total body water (TBW) percentage, higher Fat Mass (FM), associated with lower Cardiac Output (CO) and higher Total Vascular Resistance (TVR) during the second trimester. In the third trimester we didn’t find haemodynamic differences, but a significative increase in extracellular water (ECW) percentage. In patients who developed preeclampsia we found since the first trimester significative higher TVR and hypodynamic circulation, associated with lower FM percentage. Conclusions Assessment of body composition and maternal cardiac function may help to identify earlier in pregnancy, patients with different (mal) adaptations to pregnancy. Women with high TVR, hypodynamic circulation and low fat mass during the first trimester, might be at higher risk to develop preeclampsia. Patients with higher BMI and FM percentage, and increased TVR in the second trimester, might be at risk of gestational hypertension and excessive fluid retention at the end of pregnancy.

Glutathione S-transferases (GSTs) are the main phase II enzymes involved in the cellular detoxification. Through phase I and phase II detoxification reactions, the cell is able to detoxify endogenous and exogenous toxic compounds. In this study, we focused our attention on the GSTA1*-69C/T gene polymorphism (rs3957357) in order to explore its involvement in the genetic predisposition to gestational hypertension (GH).The case-control population consists of 195 subjects. The genotyping of the GSTA1*-69C/T was performed by using an RFLP-PCR technique. We calculated odds ratios (ORs), adjusted for the confounding variables, to estimate the association between GSTA1 and GH.Significant allelic differences in GSTA1*-69C/T are present between GH women and pregnant women without cardiovascular complications (p0.05). Specifically, we observed that the dominant genetic model best explains the observed genetic association, according to the Akaike information criterion and the Bayesian information criterion.Our study highlighted a significant association between the GSTA1 gene and the risk of GH in Italian patients. In particular, the -69C/T variant was significantly associated with disease risk. Since previous studies indicated that this GSTA1 polymorphism is associated with different pregnancy-related conditions, our finding supports the notion that GSTA1 may play a key role during pregnancy.

Introduction Maternal cardiovascular system adapts to pregnancy, thanks to complex physiological mechanisms that involve cardiac output, total vascular resistance and water body distribution. Abnormalities of these adaptive mechanisms are connected with hypertensive disorders. Objective To identify patients at a high risk of developing hypertensive complications of pregnancy during the first trimester of pregnancy, through the use of non-invasive methods such as USCOM (Ultrasonic Cardiac Output Monitor) and Bioimpedance. Materials and methods We enrolled 120 healthy normotensive women during the first trimester of pregnancy obtaining all measurements with the USCOM system and Bioimpedance. Results 20 patients were excluded for a bad USCOM signal. The remaining patients ( n =100) were retrospectively divided into two groups: Group A ( n =75) TVR −5 , Group B ( n =25) TVR>1200dynesscm −5 . No statistically significant difference was identified in terms of water distribution, Fat Free Mass, Systolic/Diastolic Blood Pressure, Heart Rate, Hematocrit, Flow Time Corrected and Water Balance Index between the two groups. In contrast, higher values of the Cardiac Output, Stroke Volume, Fat Mass and Inotropy Index have been highlighted in the Group A. Moreover, in the Group A we found a better maternal–neonatal outcome and a lower incidence of hypertensive complications. Conclusions High TVR during the first weeks of gestation may be an early marker of cardiovascular maladaptation more than the evaluation of water distribution and, in particular, with respect to the single blood pressure assessment. Moreover lower values of Inotropy Index could be an indicative of the worst cardiac performance.

Objective To compare haemodynamic changes, measured noninvasively using the USCOM monitor, after combined spino-epidural anaesthesia and after administration of two different uterotonic drugs, oxytocin and carbetocin, in a population of pregnant women during elective caesarean delivery. Methods Haemodynamic measurements were obtained with the USCOM system, by positioning a probe at maternal suprasternal notch (SSN) until the aortic valve flow's profile was optimally identified. Evaluations of the haemodynamic profile were obtained in seven different moments: before anaesthesia; during skin incision; 60, 180 and 300s after administration of uterotonic drug, at closure of the uterus, at closure of the skin. Doses of uterotonic drugs were: Oxytocin 5UI in 500cc NaCl eV, Carbetocin 100mcg in bolus eV. Main measured parameters were: heart rate, mean blood pressure, stroke volume, cardiac output and total vascular resistance. Results We enrolled 32 pregnant women. Patients were randomized in two groups: oxytocin and carbetocin. A reduction in mean blood pressure, a reduction of total vascular resistance and an increase of cardiac output and of stroke volume were seen, while heart rate values remained stable in both treatment groups. No statistically significant differences were found. Discussion Administration of carbetocin is associated with a substantial global haemodynamic stability in patients undergoing elective caesarean section without any difference with oxytocin. This observation allows us to consider carbetocin comparable to oxytocin, with minimum haemodynamic impact on the maternal circulation. This minimal effect on global haemodynamic stability might extend the use of this uterotonic drug in patients at high haemorrhagic risk with preeclampsia.

Background: An increase in total body water is common in normal pregnancy. It is thought to be an important mechanism of maternal adaptation to pregnancy. Objective: The aim of the present study was to assess longitudinal changes in body water compartments in pregnant women and to correlate these measurements with the course of pregnancy. Design: One hundred seventy-three pregnant women with apparently normal, single pregnancies participated in this longitudinal study. Anthropometric measurements and multifrequency bioelectrical impedance were performed during the first, second, and third trimesters of pregnancy. Results: One hundred three of the women completed all of the measurements; 50 of the women had a normal pregnancy and 13 had gestational hypertension. Total body water, extracellular water, and intracellular water values in normal pregnancies showed a significant, progressive increase throughout pregnancy. In women with gestational hypertension, total body water, extracellular water, and intracellular water values showed an opposite trend, suggesting a lack of plasma volume expansion through fluid-retention mechanisms. Conclusions: Our results show that multifrequency bioelectrical impedance analysis can be used to monitor variations in body water compartments in normal pregnancy and detect gestational hypertension.

Objective Most studies during pregnancy have assessed maternal left ventricular (LV) function by load-dependent indices, assessing only chamber function. The aim of this study was to assess afterload-adjusted LV myocardial and chamber systolic function at 24 weeks’ gestation and 6 months postpartum in high-risk normotensive pregnant women. Methods A group of 118 high-risk women with bilateral notching of the uterine arteries underwent an echocardiographic examination to evaluate midwall mechanics (midwall shortening (mFS%) and stress-corrected midwall shortening (SCmFS%)) of the LV at 24 weeks’ gestation and 6 months postpartum. Patients were followed until delivery and pregnancies were classified retrospectively as uneventful (uncomplicated outcome) or complicated. A control group of 54 low-risk women with uneventful pregnancies without bilateral notching was also enrolled. Results The pregnancy was uneventful in 74 (62.7%) women, whereas 44 (37.3%) developed complications. At 24 weeks’ gestation, mFS% and SCmFS% were greater in the uncomplicated-outcome compared with the complicated-outcome group (25.9 ± 4.8 vs 18.8 ± 5.0%, P 0.001 and 107.9 ± 18.4 vs 77.9 ± 20.7%, P 0.001 , respectively). At 6 months postpartum, SCmFS% remained greater in the uncomplicated-outcome compared with the complicated-outcome group (100.4 ± 21.6 vs 87.8 ± 19.1, P 0.05 ). In the uncomplicated outcome group, SCmFS% was higher during pregnancy than it was postpartum, whereas in the complicated outcome group, it was lower during pregnancy than it was postpartum ( P 0.05 ). Conclusions Maternal cardiac midwall mechanics appear to be enhanced (SCmFS% increased compared with controls) during pregnancy compared with postpartum in high-risk patients with uncomplicated pregnancy, whereas midwall mechanics are depressed both during pregnancy and postpartum in patients with pregnancy complications

Introduction Maternal cardiovascular system adapts to pregnancy thanks to complex physiological mechanisms that involve cardiac output, total vascular resistance (TVR) and water body distribution. Abnormalities of this adaptive mechanism are connected with hypertensive disorders and foetal growth restriction. Moreover, maternal serum PAPP-A is considered a biochemical marker extensively used for the first trimester screening of PE. Objective To identify patients at high risk of developing hypertensive complications of pregnancy during the first trimester through the use of non-invasive methods such as USCOM (Ultrasonic Cardiac Output Monitor), bioimpedance and biochemical marker. Materials and Methods We enrolled 96 healthy normotensive women with normal Body Mass Index during the first trimester of pregnancy (from 11+0 to 13+6weeks of gestation) obtaining all measurements with the USCOM system, Bioimpedance and collecting MoM values of PAPP-A Results Patients were divided into two groups: Group A ( n =54) with TVR n =42) with TVR >1200dynesseccm −5 . 10% ( n =10) of our study population developed pregnancy complications as IUGR and hypertensive disorders. In this group 81% of patients presented high TVR values and 37% PAPP-A p Conclusions High TVR and lower Fat Mass during the first weeks of gestation may be an early marker of cardiovascular maladaptation more than the evaluation of PAPP-A values and blood pressure assessment.

Objective: To ascertain the diagnostic ability of a computerized fetal heart rate (FHR) analysis system in the identification of patients at risk of fetal distress in labor. Study design: Five-hundred and seventy-seven healthy term pregnancies were enrolled in a prospective, cross-sectional study and subdivided into two groups, with (n = 90) or without (n = 487) fetal distress in labor. Computerized FHR recordings were performed periodically and regression analysis was performed in a univariate and multivariate way to assess the ability of the last FHR recording in the prediction of subsequent fetal distress. Results: The two groups showed a significant difference in almost all of the FHR parameters studied. The multivariate analysis showed that only the FHR baseline and the percentage of small accelerations were independently and significantly related to the labor outcome. The combination of these two parameters reaches a sensitivity of 45%, specificity of 91%, positive predictive value of 48% and negative predictive value of 90%, with an overall accuracy of 84%. Conclusions: The increase in FHR baseline and in small FHR accelerations can be major factors in the prediction of subsequent fetal distress in healthy term fetuses.

In pregnancy there is an increase in maternal cardiac output (CO) and a reduction in total vascular resistance (TVR). Abnormalities of this adaptive mechanisms lead to numerous disorders of pregnancy. Moreover the mother's body water composition undergoes important modifications in total body water (TBW), extracellular and intracellular body water (EBW, IBW).Aim of the study is to identify a group of patients at high risk of developing hypertensive complications of pregnancy in frist trimester.To investigate hemodynamic changes and distribution of body water during the frist trimester of pregnancy, we conducted an observational study. We evaluated CO, TVR and Time Flow Corrected (TFc) with the USCOM system, a non invasive method. Patients were, also, subjected to BIA (Body Impedance Assessment).We enrolled 120 healthy pregnant women. 20 patients, were excluded for bad signal. Absolute values of haemodynamic and body impedance measures are shown in Fig. 1. Patients were divided in two groups:Group A with TVR1200 dyne and Group B with TVR1200 dyne. CO values were higher in group B. There wasn't significant differences in TBW, haematocrit, TFc and WBI (water balance index: TBW/Hct) between the two groups.Our results show that at costant values of TBW, Hct and WBI,we can find difference in term of TVR and CO in the first trimester of pregnancy. These parameters may improve the accuracy of screening in clinical practice.

sometimes it is necessary. It is indicated to deliver when some specific maternal or fetal conditions develop. Maternal indications for delivery include: platelet count under 100,000, progressive liver function deterioration, progressive renal function deterioration, suspected abruptio placentae, refractory severe hypertension (>160/110), persistent severe headache or visual changes, persistent severe epigastric pain or emesis. Fetal indications for delivery are: severe fetal intrauterine growth retardation, low umbilical artery systolic/diastolic ratio by doppler ultrasound, non-reassuring fetal testing, oligohydramnios. If the gestation is greater than 34 weeks, delivery after stabilization is recommended.

The enzymatic activities of Na+/K+ ATPase and Ca2+ ATPase were determined on erythrocyte membranes from 9 normotensive and 9 gestational hypertensive pregnant women near term. A reduction in the activity of the Na+/K+ ATPase and a relative increase in the activity of the Ca2+ ATPase were found in the hypertensive patients, possibly due to a conformational alteration of erythrocyte membranes. This observation supports the possible role of the transmembrane cation transport in the pathogenesis of gestational hypertension.