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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.

To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR). A prospective European multicenter observational study included women with a singleton pregnancy, 32 856 women had 2770 measurements; 696 (81 %) had more than one measurement (median 3 (IQR 2-4). At inclusion, 63 (7 %) a UCR ≥ 0.9. These delivered earlier and had a lower birth weight and higher incidence of adverse outcome (30 % vs. 9 %, relative risk 3.2; 95 %CI 2.1-5.0) than women with a normal UCR at inclusion. Repeated measurements after an abnormal UCR at inclusion were abnormal again in 67 % (95 %CI 55-80), but after a normal UCR the chance of finding an abnormal UCR was 6 % (95 %CI 5-7 %). The risk of composite adverse outcome was similar using the first or subsequent UCR values. An abnormal UCR is likely to be abnormal again at a later measurement, while after a normal UCR the chance of an abnormal UCR is 5-7 % when repeated weekly. Repeated measurements do not predict outcome better than the first measurement, most likely due to the most compromised fetuses being delivered after an abnormal UCR.ZIEL: Beurteilung der longitudinalen Variation der umbilikozerebralen Ratio (UCR) der Pulsatilitätsindizes bei später fetaler Wachstumsrestriktion (FGR). Eine prospektive europäische multizentrische Beobachtungsstudie schloss Frauen mit Einlingsschwangerschaft (32 856 Frauen hatten 2770 Messungen; 696 (81 %) hatten mehr als eine Messung (Median 3, IQR 2–4). Bei Einschluss hatten 63 (7 %) eine UCR ≥ 0,9. Diese entbanden früher und hatten ein niedrigeres Geburtsgewicht und eine höhere Inzidenz für einen unerwünschten Outcome (30 % vs. 9 %, relatives Risiko 3,2; 95 %-KI 2,1–5,0) im Vergleich zu Frauen mit normaler UCR bei Einschluss. Wiederholte Messungen nach abnormaler UCR bei Einschluss waren in 67 % (95 %-KI 55–80) erneut abnormal, aber nach einer normalen UCR betrug die Wahrscheinlichkeit, eine abnormale UCR zu finden, 6 % (95 %-KI 5–7 %). Das Risiko für einen kombinierten unerwünschten Outcome war ähnlich, wenn man den ersten oder den nachfolgenden UCR-Wert verwendete. Eine abnormale UCR ist wahrscheinlich bei einer späteren Messung wieder abnormal, während nach einer normalen UCR die Wahrscheinlichkeit einer abnormalen UCR bei wöchentlicher Wiederholung 5–7 % beträgt. Wiederholte Messungen sagen das Ergebnis nicht besser voraus als die erste Messung, was höchstwahrscheinlich darauf zurückzuführen ist, dass die am stärksten gefährdeten Föten nach einer abnormalen UCR entbunden werden.

The aim of the study is to compare maternal hemodynamic adaptations in gestational diabetes (GDM) versus healthy pregnancies. A prospective case–control study was conducted, comparing 69 singleton pregnancies with GDM and 128 controls, recruited between September 2018 and April 2019 in Maternal–Fetal Medicine Unit, Careggi University Hospital, Florence, Italy. Hemodynamic assessment by UltraSonic Cardiac Output Monitor (USCOM) was performed in both groups in four gestational age intervals: 17–20 weeks (only in early GDM cases), 26–30 weeks, 32–35 weeks and 36–39 weeks. We evaluated six hemodynamic parameters comparing GDM cases versus controls: cardiac output (CO), cardiac index (CI), stroke volume (SV), total vascular resistance (TVR), inotropy index (INO) and potential to kinetic energy ratio (PKR). GDM group had significantly lower values of CO and SV than controls from the early third trimester (26–30 weeks) until term (p

Isolated intrauterine growth restriction (IUGR) and preeclampsia (PE) share common placental pathogenesis. Differently from IUGR, PE is a systemic disorder which may also affect liver and brain. Early diagnosis of these conditions may optimize maternal and fetal management. Aim of this study was to assess whether Epidermal Growth Factor-Like domain 7 (EGFL7) dosage in maternal blood discriminates between isolated IUGR and PE. A total of 116 women were enrolled in this case–control study: 12 non-pregnant women, 34 healthy pregnant women, 34 women presenting with isolated IUGR and 36 presenting with PE. Levels of circulating EGFL7 and other known pro- and anti-angiogenic factors were measured by ELISA at different gestational ages (GA). Between 22–25 weeks of gestation, EGFL7 levels in early-onset PE (e-PE) plasma samples were significantly higher than those measured in controls or isolated IUGR samples (69.86 ± 6.17 vs. 19.8 ± 2.5 or 18.8 ± 2.8 µg/ml, respectively). Between 26–34 weeks, EGFL7 levels remained significantly higher in e-PE compared to IUGR. At term, circulating and placental EGFL7 levels were comparable between IUGR and late-onset PE (l-PE). In contrast, circulating levels of PlGF were decreased in both IUGR- and PE- complicated pregnancies, while levels of both sFLT-1 and sENDOGLIN were increased in both conditions. In conclusion, EGFL7 significantly discriminates between isolated IUGR and PE.

SARS-CoV-2 represents the greatest epidemiological, clinical, and social challenge the human being has had to face in this century. SARS-CoV-2 is not merely a respiratory virus, as its target cells range from upper airway respiratory cells to pulmonary cells but also and above all to the cardiovascular cells, such as pericytes and endothelial cells. Indeed, the pathology related to SARS-CoV-2, COVID-19, may be defined as a thromboinflammatory syndrome in its most severe form, characterized by sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulopathy (DIC), which is prevalent in individuals already presenting a chronic level of inflammation (e.g., obese individuals, elderly) and hypertension. Pregnancy is not only an inflammatory-prone condition but is characterized by a consistent rearrangement of the blood circulation and coagulation profile. Cardiac output increases while arterial systolic and diastolic pressure decrease, regardless of the activation of the RAS system. ACE2, the SARS-CoV-2 entry receptor into the host cells, which transforms Ang II in Ang 1–7, is highly expressed in endothelial, smooth muscle cells and pericytes of placental villi, regulating blood pressure and fetal development. Pre-eclampsia is a pregnancy disorder characterized by hypertension and low levels of ACE2, endothelial dysfunction, and a high production of pro-inflammatory cytokines, resembling COVID-19 manifestations. Whereas pre-eclampsia and COVID-19 have overlapping clinical features, a role for SARS-CoV-2 as a leading cause of pre-eclampsia in COVID-19 positive pregnant women has not been clarified yet. In this mini-review, we will explore the possibility of the existence of such a link, focusing on the role of endothelial dysfunction and RAS in both pre-eclampsia and SARS-CoV-2-induced COVID-19 pathogenesis.

To improve identification of fetal growth restriction (FGR) by means of umbilical venous flow (QUV) and maternal hemodynamics, including systemic vascular resistance (SVR) and cardiac output (CO), in order to distinguish between FGR and SGA.We enrolled 68 pregnancies (36 SGA, 8 early FGR and 24 late FGR) who underwent a complete fetal hemodynamic examination including QUV and a noninvasive maternal hemodynamics assessment by means of USCOM.In comparison with SGA, QUV and corrected for estimated fetal weight QUV (cQUV) were significantly lower in early and late-FGR. In addition, maternal CO was lower in early and late-FGR, while SVR was lower only in early-onset FGR. According to ROC analysis, cQUV centile (AUC 0.92, 0.72) was the best parameter for the prediction of SGA before and after 32 weeks, followed by SVR and CO. For all parameters, the prediction was always better in the case of early-onset FGR32 weeks.UV flow and maternal hemodynamics examination are useful tools to accurately discern between SGA and FGR.

The aim of this study was to evaluate early pregnancy differences in maternal hemodynamics, cardiac geometry and function, between chronic hypertensive (CH) patients with and without the development of feto-maternal complications later in pregnancy.We performed a case-control study on nulliparous CH treated patients. From a group of CH patients referred to our outpatient clinic at 4-6 weeks for a clinical evaluation the first consecutive 30 patients with subsequent complications (superimposed PE, abruptio placentae, uncontrolled severe hypertension with delivery34 weeks, HELLP syndrome, FGR, perinatal death) were enrolled; the first 2 CH women with uneventful pregnancy referred after the case were enrolled as controls for a total of 60 patients. All patients were shifted to alpha-methyl dopa at the beginning of pregnancy and were submitted to an echocardiographic evaluation to assess the maternal hemodynamics, cardiac geometry, diastolic and systolic function.Patients developing complications had a lower early pregnancy heart rate (73 ± 11 vs. 82 ± 11 bpm), cardiac output (5.23 ± 1.2 vs. 6.5 ± 1.3 L/min,CH treated patients developing maternal and/or fetal complications show early pregnancy altered cardiac geometry, diastolic and systolic dysfunction, and impaired hemodynamics with a high resistance circulation.

Anti-NMDAR encephalitis is an autoimmune syndrome associated with antibodies against NMDA receptors. In some cases, it is associated with various tumors; one of them is ovarian teratoma, which mostly affects women below the age of 30 years. Here, we report a case of ovarian teratoma associated with anti-NMDAR encephalitis treated with both laparoscopic surgery and immunotherapy. Multidisciplinary approach is the cornerstone for the management of this syndrome.

AIMS To evaluate the efficacy of Ospemifene in the vaginal health index (VHI), in the vulvovaginal vascular perfusion and to assess its impact on quality of life and sexual function. METHODS Among 52 eligible patients, 43 consecutive postmenopausal patients affected by vulvo-vaginal atrophy (VVA) or Genitourinary Syndrome (GSM) were evaluated. VVA evaluation and ultrasound of the vulvo-vaginal vascularization by sampling the pulsatility index (PI) of clitoris dorsal artery were performed before and after 3 months-treatment with Ospemifene. The 36-Item Short Form Survey (SF-36) for the quality-of-life assessment before and after 3 months were available for all women; instead Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS) questionnaires for the sexual function evaluation were performed for sexually active women in the study. The Patient Impression of Global Improvement (PGI-I) after 3 months of treatment was also calculated. RESULTS The number of sexually active women significantly increased after 3 months [26 (60.46%) vs 35 (81.39%); p=0.01]. The mean number of intercourses during the treatment increased (12.87 ± 3.43 vs 15.79 ± 3.12, p=0.03). The PI of clitoris dorsal artery has significantly changed before and after treatment respectively [PI (1.69 ± 0.42 vs 1.28 ± 0.45, p=0.001) RI (0.74 ± 0.11 vs 0.54 ± 0.15, p=0.001)]. The FSFI, FSDS and SF-36 questionnaires scores showed a significant improvement after 3 months. VHI and PI were the independent factors of a lower FSFI after 3 months of treatment at multivariate analysis. CONCLUSIONS Ospemifene improve the VHI and vulvovaginal vascular perfusion demonstrating a positive impact on sexual function and quality of life.

Objectives: To assess umbilical vein (UV) blood flow in fetal growth restriction (FGR) and in pregnancy with small for gestational age (SGA) fetus. To evaluate the predictive capacity of UV blood flow (QUV) in the discrimination of SGA fetuses from FGR before and after 32 weeks of pregnancy. Methods: Sixty-five women with a recent diagnosis of FGR or SGA fetuses were enrolled and underwent a complete fetal Doppler examination comprehending QUV. We collected SGA (n = 34), early-FGR (n = 9), and late-FGR (n = 22) fetuses. Results: UV diameter was lower in early and late-FGR compared to SGA, while time-averaged maximum velocity (TAMXV) was lower only in early-FGR. UV blood flow (QUV) and QUV corrected for estimated fetal weight (cQUV) were significantly lower in early-FGR and late-FGR compared to SGA. The receiver operating characteristic (ROC) curves analysis of cQUV showed a significant predictive capacity for SGA diagnosis before and after 32 weeks. Conclusions: The evaluation of UV blood flow allows distinguishing SGA fetuses from FGR. The assessment of UV flow should be taken into consideration in future research of new parameters to differentiate SGA from FGR.

Intrauterine growth restriction (IUGR) is a pathological condition of pregnancy with high perinatal mortality and morbidity, characterized by inadequate fetal growth associated to altered maternal hemodynamics with impaired uteroplacental blood flow and placental insufficiency. To date, iatrogenic premature delivery remains the elective therapeutic strategy. However, in recent years the possibility of a therapeutic approach with vasodilators and myorelaxants, such as nitric oxide (NO) donors, has gained interest. NO controls many endothelial cell functions, including angiogenesis and vascular permeability, by regulating the expression of angiogenic factors, such as Vascular Endothelial Growth Factor. In the present study, we investigated if treatment of pregnancies complicated by IUGR with NO donors affects the expression of Epidermal Growth Factor-Like Domain 7 (EGFL7), a secreted endothelial factor, previously demonstrated to be expressed by both endothelial and trophoblast cells and involved in proper placental development. NO donor treatment induced placental levels of EGFL7 and, in association with oral fluids, significantly improved fetal growth. Ex vivo experiments confirmed that NO donors increased expression and secretion of EGFL7 by villous explants. To specifically investigate the potential response of trophoblast cells to NO, we treated HTR8-sVneo cells with NO donors and observed induction of EGFL7 expression. Altogether, our findings indicate that NO induces endothelial and trophoblast expression of EGFL7 in the placenta and improves fetal growth, suggesting a correlation between placental levels of EGFL7 and pregnancy outcome.

We investigate the relationship between maternal cardiovascular (CV) function and fetal Doppler changes in healthy pregnancies and those with pre-eclampsia (PE), small for gestational age (SGA) or fetal growth restriction (FGR). This was a three-centre prospective study, where CV assessment was performed using inert gas rebreathing, continuous Doppler or impedance cardiography. Maternal cardiac output (CO) and peripheral vascular resistance (PVR) were analysed in relation to the uterine artery, umbilical artery (UA) and middle cerebral artery (MCA) pulsatility indices (PI, expressed as z-scores by gestational week) using polynomial regression analyses, and in relation to the presence of absent/reversed end diastolic (ARED) flow in the UA. We included 81 healthy controls, 47 women with PE, 65 with SGA/FGR and 40 with PE + SGA/FGR. Maternal CO was inversely related to fetal UA PI and positively related to MCA PI, the opposite was observed for PVR, which was also positively associated with increased uterine artery impedance. CO was lower (z-score 97, p = 0.02) and PVR higher (z-score 2.88, p = 0.02) with UA ARED flow. We report that maternal CV dysfunction is associated with fetal vascular changes, namely raised impedance in the fetal-placental circulation and low impedance in the fetal cerebral vessels. These findings are most evident with critical UA Doppler changes and represent a potential mechanism for therapeutic intervention.

Hypertensive disorders of pregnancy remain a leading cause of maternal and fetal morbidity and mortality [1].There is no consensus on the relative efficacy and safety of the medications to treat se...

Chronic hypertension complicates around 3% of all pregnancies and is associated with an increased risk for pregnancy complications such as superimposed preeclampsia, fetal growth restriction, preterm delivery, and stillbirth, reaching a rate of complications of up to 25-28%.We performed an echocardiographic study to evaluate pre-pregnancy cardiac geometry and function, along with the hemodynamic features of treated chronic hypertension patients, searching for a possible correlation with the development of feto-maternal complications and with pre-pregnancy therapy.This was a prospective observational cohort study of 192 consecutive patients receiving treatment for chronic hypertension (calcium channel blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, α1-adrenoceptor antagonists, and/or diuretics). Patients underwent echocardiography before pregnancy, assessing left ventricular morphology and function, cardiac output, and total vascular resistance. Pre-pregnancy therapy was noted, patients were shifted to α-methyldopa right before pregnancy, and were followed until delivery, noting major early (34weeks' gestation) and late (≥34 weeks' gestation) complications. Comparisons among the 3 groups (ie, those with no complications, early complications, and late complications) were performed with 1-way analysis of variance with Student-Newman-Keuls correction for multiple comparisons. The Mann-Whitney U test was used for non-normally distributed data. Comparison of proportions was used as appropriate. Receiver operating characteristic curve analysis was used to identify cutoff values of diastolic dysfunction in this population using the E/e' ratio, and separate cutoff of values for total vascular resistance for the prediction of early and late complications of pregnancy. Binary univariate and multivariate logistic regression as well as Cox proportional hazards regression were used to evaluate the possible correlation among angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and/or calcium channel blocker pre-pregnancy therapy, cardiovascular features, and the risk for subsequent early and late complications of pregnancy.Of 192 patients, 141 had no complications, and 51 had a complicated pregnancy (24 had early complications and 27 had late complications). Concentric geometry was more frequent in those women with early versus late and no complications (50% vs 13.5% and 11.1%, respectively; P.05), whereas eccentric hypertrophy was more represented in women with late versus early and no complications (32% versus 12.5% and 1.4%, respectively; P.05). The receiver operating characteristic curve showed an E/e' ratio value7.65 (sensitivity, 59.6%; specificity, 68.6%) as a predictor of subsequent complications of pregnancy, whereas total vascular resistance1048 (sensitivity, 83.7%; specificity, 55.6%) was predictive for late complications and total vascular resistance1498 (sensitivity, 87.5%; specificity, 78.0%) for the early complications of pregnancy. Univariate analysis showed that the following parameters were predictive for complications of pregnancy: altered geometry of the left ventricle (odds ratio, 5.94; 95% confidence interval, 2.90-12.19), diastolic dysfunction (odds ratio, 3.22; 95% confidence interval, 1.63-6.37), altered total vascular resistance (odds ratio, 3.52; 95% confidence interval, 1.78-6.97), and pre-pregnancy therapy without calcium channel blockers/angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (odds ratio, 2.73; 95% confidence interval, 1.37-5.42). These parameters, except for altered total vascular resistance, were independent predictors in the multivariate analysis corrected for body mass index, heart rate, parity, and mean arterial pressure.Chronic hypertension patients with pre-pregnancy cardiac remodeling and dysfunction more often develop early and late complications of pregnancy. Pre-pregnancy therapy for chronic hypertension patients with calcium channel blockers and/or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers may positively influence cardiac profiles and the outcome of a future pregnancy with a reduced rate of complications.

OBJECTIVES To test the efficacy of maternal activity restriction for reducing peripheral vascular resistance in normotensive pregnant women with raised total vascular resistance (TVR) and to evaluate its effect on fetal growth. METHODS This was a prospective case-control study of 30 women enrolled between 27 and 29 weeks' gestation. All patients met the following criteria: normal blood pressure before and during pregnancy, TVR between 1300 and 1400 dynes × s/cm5 at enrolment, normal fetal Doppler parameters at enrolment and abdominal circumference between the 10th and 25th centiles. Patients were assigned to activity restriction (activity-restriction group; n = 15) or no treatment (control group; n = 15) and were assessed after 4 weeks for TVR and fetal growth. RESULTS TVR at enrolment and estimated fetal weight centile were similar in the activity-restriction group vs controls (1358 ± 26 vs 1353 ± 30 dynes × s/cm5 ; 18th ± 4 vs 19th ± 4 centile; P = NS). After 4 weeks, the activity-restriction group compared with controls showed significantly lower TVR (1165 ± 159 vs 1314 ± 190 dynes × s/cm5 ; P

Objective To evaluate the effect on maternal cardiovascular parameters of treatment with a nitric oxide (NO) donor and plasma volume expansion in pregnancies complicated by fetal growth restriction (FGR). Methods Twenty-six pregnant women with a diagnosis of FGR were treated with transdermal patches of a NO donor and plasma volume expansion by co-administration of oral fluids. We compared the treated group to a historical control group of untreated FGR patients. Hemodynamic indices were obtained using the UltraSonic Cardiac Output Monitor system. Results At diagnosis, the two groups were similar in terms of maternal and hemodynamic characteristics. In the treated group, we found a significant increase in maternal cardiac output and stroke volume and a decrease in systemic vascular resistance after 2 weeks of therapy. No significant differences were found 2 weeks after diagnosis in the untreated group. The treated group delivered infants with higher birth-weight centile than did the untreated control group. Conclusions The combined therapeutic approach of NO donor administration and plasma volume expansion in FGR apparently improves significantly maternal hemodynamic indices. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Objective To determine if hemodynamic assessment in 'low-risk' pregnant women at term with an appropriate-for-gestational age (AGA) fetus can improve the identification of patients who will suffer maternal or fetal/neonatal complications during labor. Methods This was a prospective observational study of 77 women with low-risk term pregnancy and AGA fetus, in the early stages of labor. Hemodynamic indices were obtained using the UltraSonic Cardiac Output Monitor (USCOM® ) system. Patients were followed until the end of labor to identify fetal/neonatal and maternal outcomes, and those which developed complications of labor were compared with those delivering without complications. Results Eleven (14.3%) patients had a complication during labor: in seven there was fetal distress and in four there were maternal complications (postpartum hemorrhage and/or uterine atony). Patients who developed complications during labor had lower cardiac output (5.6 ± 1.0 vs 6.7 ± 1.3 L/min, P = 0.01) and cardiac index (3.1 ± 0.6 vs 3.5 ± 0.7 L/min/m2 , P = 0.04), and higher total vascular resistance (1195.3 ± 205.3 vs 1017.8 ± 225.6 dynes × s/cm5 , P = 0.017) early in labor, compared with those who did not develop complications. Receiver-operating characteristics curve analysis to determine cut-offs showed cardiac output ≤ 5.8 L/min (sensitivity, 81.8%; specificity, 69.7%), cardiac index ≤ 2.9 L/min/m2 (sensitivity, 63.6%; specificity, 76.9%) and total vascular resistance > 1069 dynes × s/cm5 (sensitivity, 81.8%; specificity, 63.6%) to best predict maternal or fetal/neonatal complications. Conclusions The study of maternal cardiovascular adaptation at the end of pregnancy could help to identify low-risk patients who may develop complications during labor. In particular, low cardiac output and high total vascular resistance are apparently associated with higher risk of fetal distress or maternal complications. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

The recent demonstration of the effectiveness of low-dose aspirin administered from the first trimester in the prevention of preeclampsia will probably lead to establishing and radicating the “inverted pyramid” screening model for preeclampsia. Such a multiparametric approach for the screening of preeclampsia in the first trimester, albeit highly sensitive in identifying early-onset disease, is poor at screening the forms of preeclampsia occurring close to term. Late-onset preeclampsia is 3 to 6 times more common than early-onset preeclampsia and currently represents the major determinant of maternal morbidity related to hypertensive disorders of the pregnancy. On this ground, we discuss our idea to construct a second “screening checkpoint” in the third trimester with the aim of reassessing the risk of preeclampsia of those women who screened negative in the first trimester. If implemented, the sequential screening model we propose would convert the “inverted pyramid model” into an “arrow model” for the antenatal care of preeclampsia.

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.

Maternal hemodynamics plays a major role during pregnancy and its evaluation is fundamental to understand obstetric conditions. The modern opinion about maternal hemodynamics assessment is to shift focus from single hemodynamic parameters to the whole hemodynamic profile. Our aim is to create a simple, intuitive, and easily understandable graphing technique to evaluate the main hemodynamic parameters.We enrolled 531 pregnant women without maternal or fetal disease. One hundred and forty five in the first trimester of pregnancy, 258 in the second one and 128 in the third one. We performed hemodynamic assessment with ultrasonic cardiac output monitor method. We selected the six main parameters: cardiac output, systemic vascular resistance, heart rate, potential-to-kinetic energy ratio, inotropy index, and stroke volume variation. We chose the radar chart to display the multivariate data of the hemodynamic measurement of the patient in evaluation.We have obtained mean and deviation standard values for the six main hemodynamic parameters in every trimester. They deeply change during the pregnancy, so it is correct to compare a new hemodynamic measurement with the mean values for the specific trimester in order to evaluate any possible alterations. In fact, once a new hemodynamic assessment is performed, we calculate theAt the end of a hemodynamic exam, the physician can input the data in the program obtaining a graphic representation. Using this technique, which simultaneously evaluates six hemodynamic parameters, it is possible to easily understand the patient's hemodynamic status. By converting the parameters values in

Cardiac output (CO), along with blood pressure and vascular resistance, is one of the most important parameters of maternal hemodynamic function. Substantial changes in CO occur in normal pregnancy and in most obstetric complications. With the development of several non-invasive techniques for the measurement of CO, there is a growing interest in the determination of this parameter in pregnancy. These techniques were initially developed for use in critical-care settings and were subsequently adopted in obstetrics, often without appropriate validation for use in pregnancy. In this article, methods and devices for the measurement of CO are described and compared, and recommendations are formulated for their use in pregnancy, with the aim of standardizing the assessment of CO and peripheral vascular resistance in clinical practice and research studies on maternal hemodynamics. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Objective To evaluate the maternal hemodynamic profile in women with a diagnosis of threatened preterm delivery (TPD) in order to understand the possible pathophysiologic mechanism leading to an increased lifetime risk for future cardiovascular disease. Methods Patients with a diagnosis of TPD were enrolled and assessed using a non-invasive method (USCOM®) for the determination of hemodynamic parameters. Vaginal and rectal swabs were taken, cervical length, blood inflammatory indices, fetal blood-vessel Doppler velocimetry were measured and gestational age at the time of delivery and neonatal outcomes were noted. Results A total of 68 patients were enrolled and included in the analysis. The population was divided into two groups according to total vascular resistance (TVR): Group A with a TVR of ≤ 1000 dynes × s/cm5 (n = 48) and Group B with a TVR of > 1000 dynes × s/cm5 (n = 20). C-reactive protein (CRP) was higher in Group B than in Group A, suggesting a systemic inflammation status. Group B delivered earlier (32 + 4 weeks vs 38 + 2 weeks; P 1000 dynes × s/cm5 and elevated levels of CRP are at high risk of preterm delivery. An impaired maternal cardiovascular adaptation during pregnancy in these patients might suggest a possible higher risk for subsequent future cardiovascular disease. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

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.

Hypertensive disorders of pregnancy (HDP) are a major cause of maternal and fetal morbidity and death.[1][1] To date, the prediction of these disorders and their complications has been based on many clinical characteristics, hemodynamics, and placental indicators (either with Doppler evaluation of

Background: Early-onset fetal growth restriction represents a particular dilemma in clinical management balancing the risk of iatrogenic prematurity with waiting for the fetus to gain more maturity, while being exposed to the risk of intrauterine death or the sequelae of acidosis. Objective: The Trial of Umbilical and Fetal Flow in Europe was a European, multicenter, randomized trial aimed to determine according to which criteria delivery should be triggered in early fetal growth restriction. We present the key findings of the primary and secondary analyses. Study Design: Women with fetal abdominal circumference 95th percentile between 26-32 weeks were randomized to 1 of 3 monitoring and delivery protocols. These were: fetal heart rate variability based on computerized cardiotocography; and early or late ductus venosus Doppler changes. A safety net based on fetal heart rate abnormalities or umbilical Doppler changes mandated delivery irrespective of randomized group. The primary outcome was normal neurodevelopmental outcome at 2 years. Results: Among 511 women randomized, 362/503 (72%) had associated hypertensive conditions. In all, 463/503 (92%) of fetuses survived and cerebral palsy occurred in 6/443 (1%) with known outcome. Among all women there was no difference in outcome based on randomized group; however, of survivors, significantly more fetuses randomized to the late ductus venosus group had a normal outcome (133/144; 95%) than those randomized to computerized cardiotocography alone (111/131; 85%). In 118/310 (38%) of babies delivered

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.

BACKGROUND: Reduced fetal middle cerebral artery Doppler impedance is associated with hypoxemia in fetal growth restriction. It remains unclear as to whether this finding could be useful in timing delivery, especially in the third trimester. In this regard there is a paucity of evidence from prospective studies.OBJECTIVES: The aim of this study was to determine whether there is an association between middle cerebral artery Doppler impedance and its ratio with the umbilical artery in relation to neonatal and 2 year infant outcome in early fetal growth restriction (26(+0) -31(+6) weeks of gestation). Additionally we sought to explore which ratio is more informative for clinical use.STUDY DESIGN: This is a secondary analysis from the Trial of Randomized Umbilical and Fetal Flow in Europe, a prospective, multicenter, randomized management study on different antenatal monitoring strategies (ductus venosus Doppler changes and computerized cardiotocography short-term variation) in fetal growth restriction diagnosed between 26(+0) and 31(+6) weeks. We analyzed women with middle cerebral artery Doppler measurement at study entry and within 1 week before delivery and with complete postnatal follow-up (374 of 503). The primary outcome was survival without neurodevelopmental impairment at 2 years corrected for prematurity. Neonatal outcome was defined as survival until first discharge home without severe neonatal morbidity. Z-scores were calculated for middle cerebral artery pulsatility index and both umbilicocerebral and cerebroplacental ratios. Odds ratios of Doppler parameter Z-scores for neonatal and 2 year infant outcome were calculated by multivariable logistic regression analysis adjusted for gestational age and birthweight p50 ratio.RESULTS: Higher middle cerebral artery pulsatility index at inclusion but not within 1 week before delivery was associated with neonatal survival without severe morbidity (odds ratio, 1.24; 95% confidence interval, 1.02-1.52). Middle cerebral artery pulsatility index Z-score and umbilicocerebral ratio Z-score at inclusion were associated with 2 year survival with normal neurodevelopmental outcome (odds ratio, 1.33; 95% confidence interval, 1.03-1.72, and odds ratio, 0.88; 95% confidence interval, 0.78-0.99, respectively) as were gestation at delivery and birthweight p50 ratio (odds ratio, 1.41; 95% confidence interval, 1.20-1.66, and odds ratio, 1.86; 95% confidence interval, 1.33-2.60, respectively). When comparing cerebroplacental ratio against umbilicocerebral ratio, the incremental range of the cerebroplacental ratio tended toward zero, whereas the umbilicocerebral ratio tended toward infinity as the values became more abnormal.CONCLUSION: In a monitoring protocol based on ductus venosus and cardiotocography in early fetal growth restriction (26(+0) -31(+6) weeks of gestation), the impact of middle cerebral artery Doppler and its ratios on outcome is modest and less marked than birthweight and delivery gestation. It is unlikely that middle cerebral artery Doppler and its ratios are informative in optimizing the timing of delivery in fetal growth restriction before 32 weeks of gestation. The umbilicocerebral ratio allows for a better differentiation in the abnormal range than the cerebroplacental ratio.

Objective To test if maternal hemodynamics and bioimpedance, assessed at the time of combined screening for PE, are able to identify in the first trimester of gestation normotensive non-obese patients at risk for pre-eclampsia (PE) and/or intrauterine growth restriction (IUGR). Methods One hundred and fifty healthy nulliparous non-obese women (body mass index

In 2008, the World Health Assembly endorsed the Global Noncommunicable Disease (NCD) Action Plan based on the realization that NCDs caused more deaths than communicable diseases worldwide. 1 This plan strongly advocates prevention as the most effective strategy to curb NCDs. The “Life Course Approach”, also recently highlighted in the Minsk Declaration, reflects the increasing recognition that early development impacts later-life health and disease. 1,2 Optimization of early development offers the opportunity for true primary prevention of NCDs. Developmental programming in the kidney has been recognized for over 2 decades but its contribution to the global burden of kidney diseases remains underappreciated by policy makers. 3 Given the many factors known to impact fetal kidney development, including maternal health and nutrition, exposure to stress, poverty, pollutants, drugs and infections during gestation, 3 a holistic strategy to prevent such programming effects is consistent with the “Life-Course” approach and aligns with the United Nations Sustainable Development Goals (SDG) to foster health. 2,4 Chronic kidney disease (CKD) is an important contributor to the NCD burden that has been relatively neglected in the Global NCD Action Plan, despite CKD being a major cause of hypertension, and a major risk multiplier of cardiovascular disease 1,5 While the prevalence of CKD in many lower-income countries remains unknown, CKD is more prevalent among disadvantaged populations within industrialized nations, e.g. African Americans and Aboriginal Australians. 6 People receiving dialysis or transplantation are projected to double from 2.6 million in 2010 to 5.4 million in 2030. 7 Between 2.3 and 7.1 million adult people died from lack of access to dialysis and transplantation in lower-income countries in 2010. 7 Given the clinical consequences and often prohibitively high costs of treatment, prevention and early detection are the only sustainable solutions to address this growing global burden. To address the neglected issue of developmental programming of kidney disease and hypertension, a multidisciplinary workgroup, including international expert obstetricians, neonatologists and nephrologists (see Appendix), was convened. We argue that the Global NCD Action Plan does not adequately address the impact of developmental origins of NCDs which is globally but is particularly important in low- and middle-income countries (LMICs) where developmental risk is highest and the burden of NCDs is growing fastest. 8 The working group identified the need to raise awareness of the role of developmental programming in renal disease, and suggests locally adapted preventive strategies that could have long-term benefits on health and heath cost savings worldwide, integrating obstetrical, neonatal and nephrology perspectives.

Introduction: Several studies have demonstrated the correlation between maternal obesity and pregnancy complications. Obese women seem to be at higher risk to develop late preeclampsia, which shows...

The purpose of our study was to assess cardiac function in nonpregnant women with previous early preeclampsia before a second pregnancy to highlight the cardiovascular pattern, which may take a risk for recurrent preeclampsia. Seventy-five normotensive patients with previous preeclampsia and 147 controls with a previous uneventful pregnancy were enrolled in a case-control study and submitted to echocardiographic examination in the nonpregnant state 12 to 18 months after the first delivery. All patients included in the study had pregnancy within 24 months from the echocardiographic examination and were followed until term. Twenty-two (29%) of the 75 patients developed recurrent preeclampsia. In the nonpregnant state, patients with recurrent preeclampsia compared with controls and nonrecurrent preeclampsia had lower stroke volume (63±14 mL versus 73±12 mL and 70±11 mL, P P P −1 ·cm −5 versus 1341±270 dyne·s −1 ·cm −5 and 1383±261 dyne·s −1 ·cm −5 , P 2.7 and 30.4±6.8 g/m 2.7 versus 24.8±5.0 g/m 2.7 , P

Objective Complications in early-onset mild gestational hypertension (GH) are better predicted by total peripheral vascular resistance (TPVR) > 1350 dyne than by blood pressure. We therefore aimed to assess the possible reduction of severe complications by lowering TPVR with nitric oxide (NO) donors, oral fluids and standard antihypertensive therapy in women with early-onset mild GH. Methods A group of 400 patients with early-onset (20–27 weeks' gestation) mild GH (systolic and diastolic blood pressure 1350 dyne were enrolled in a prospective non-randomized trial with sequential allocation: 100 patients were treated with nifedipine (Group A); 100 with nifedipine and NO donors (Group B); 100 with nifedipine and oral fluids (Group C); and 100 with nifedipine, NO donors and oral fluids (Group D). TPVR was checked 1 month after initiation of therapy, and the number of patients with severe maternal and fetal complications was recorded in each group. The relationship between reduction in TPVR and the frequency of severe complications was assessed. Results Severe complications developed in 51% of patients in Group A, 48% in Group B, 53% in Group C and 35% in Group D, the frequency in Group D being significantly lower than that in the other treatment groups (P < 0.05). A reduction in TPVR of < 15% predicted the occurrence of severe complications with sensitivity 95.2% and specificity 88.3%. In Group D a reduction in TPVR of ≥ 15% was more probable (odds ratio (OR) = 2.03; 95% CI, 1.15–3.60; P < 0.015) and severe complications were less probable (OR = 0.52; 95% CI, 0.29–0.91; P < 0.023). Conclusion In women with early-onset mild GH, combined treatment with NO donors, oral fluids and nifedipine optimally reduces TPVR and seems to reduce maternal and fetal complications. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

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.

Objectives 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. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

We evaluated the predictive value of elevated total vascular resistance on the outcome of pregnancy in normotensive high-risk primigravidas with bilateral notching of the uterine artery Doppler. A total of 526 high-risk primigravidas referred to the obstetrics outpatient clinic of Tor Vergata University with bilateral notching of the uterine artery at 20 to 22 weeks’ gestation were submitted to a maternal echocardiographic examination and uterine artery Doppler evaluation at 24 weeks’ gestation. Blood pressure was recorded at the time of the examination, total vascular resistance was calculated, and the geometric pattern of the left ventricle was assessed. Patients were followed until the end of pregnancy to detect fetal/maternal adverse outcomes (gestational hypertension, preeclampsia, abruptio placentae, fetal growth restriction, perinatal death, etc). A total of 111 of the 526 pregnancies showed a bilateral notch at 24 weeks’ gestation, and 97 had an adverse outcome (18.44%). The best independent predictor for maternal and fetal complications was total vascular resistance (odds ratio: 91.25; 95% CI: 39.64 to 210.05; P −5 , with a sensitivity and a specificity of 89% and 94%, respectively. A high relative wall thickness of the left ventricle (>0.37; odds ratio: 2.47; 95% CI: 1.12 to 5.44) and a hypertrophized ventricle (left ventricular mass >130 g; odds ratio: 2.52; 95% CI: 1.12 to 5.64) were also independent predictors ( P

Aim: The aims of the study were to: (i) compare the accuracy of standard ultrasonic algorithms in the estimation of fetal weight and; (ii) test two new algorithms in order to improve the global performance of birthweight prediction by adding fetal subcutaneous tissue thickness. Methods: We enrolled 398 patients who were between 34 and 42 weeks' gestation. Routine ultrasonographic biometric parameters as well as subcutaneous tissue thickness ultrasound parameters were measured. Correlation matrices between ultrasound parameters, in order to evaluate the degree of multicollinearity between these parameters, were assessed to develop a stepwise multiple regression birthweight predictive model. Results: Contributions of single ultrasound measurements in predicting birthweight were examined, by fitting Log-transformed birthweight versus single ultrasound measurements. We found that the mid-thigh tissue area was able to significantly improve the performance of the birthweight prediction process when added to the other standard ultrasound measurements. We derived two new algorithms which appeared to be better at predicting birthweight. Furthermore there was a lower minimum absolute estimation error noted when compared to other reported formulae. Conclusions: Our algorithms showed that the addition of the mid-thigh tissue evaluation in birthweight prediction was valuable in comparison to birthweight prediction models which are based on routine ultrasound parameters.