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Pregnancy has an important impact on the thyroid gland and its function. Thyroid activity changes as a consequence of the novel physiological state of pregnancy and requires a complex hormonal and metabolic adaptation, which is possible only in the presence of a perfectly functioning thyroid gland. In fact, thyroid function is crucial for the success of the implantation and the progression of pregnancy. Abnormal thyroid function is very common among childbearing age women, explaining the high incidence of thyroid diseases that occur during pregnancy. Aim of this work is to analyze the adaptive events that characterize the thyroid function during pregnancy, exploring their hormonal, metabolic and molecular mechanisms. Moreover, the interpretation of the laboratory data necessary to monitor the thyroid functioning during normal pregnancy or in the presence of thyroid abnormalities will be discussed.

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 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.

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.

We aimed at testing systemic vascular resistance (SVR) for the correct identification of early fetal growth restriction (FGR). 61 normotensive patients, gestational age 29 + 0-32 + 0, with suspected diagnosis of early FGR, were submitted to USCOM and to an ultrasound evaluation. 24 patients met the criteria of FGR, and 9 patients developed umbilical artery Doppler alterations. SVR1006 dyn s·cm

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.

The aim of this study was to assess the hemodynamic differences in women with pPROM versus physiological pregnancies.This was a prospective case control study of 15 patients with pPROM and 45 controls. Patients and controls were submitted at enrollment to a non-invasive hemodynamic evaluation with UltraSonic Cardiac Output Monitor (USCOM), and to blood tests to check white blood cells count and C-reactive protein (CRP) levels. We followed pPROM patients until delivery noting fetal/neonatal and maternal unfavorable outcomes (maternal fever, APGAR 1' and 5'7, stillbirth).Patients with pPROM showed higher values of cardiac output (9.1 ± 2.3 vs 7.1 ± 0.85, p 0.01), lower systemic vascular resistances (792.1 ± 162 vs 1006.2 ± 110.7, p 0.01), higher minute distance (32.3 ± 7.8 vs 25 ± 2.8, p 0.01), lower Potential to Kinetic Energy Ratio (16.5 ± 5.3 vs 22.4 ± 6.8, p 0.01), higher heart rate (97.5 ± 15.4 vs 82.4 ± 12, p 0.01) and higher oxygen delivery (1313.2 ± 325.8 vs 1080.7 ± 151.8, p 0.01) vs. controls. Six out of 15 pPROM patients had an unfavorable outcome. There were no significant differences in CRP levels and WBC count at admission in the two pPROM subgroups, whereas maternal hemodynamics was characterized by lower SVR (718 ± 72 vs 863 ± 123, p = 0.02) in subsequently complicated patients.Maternal hemodynamics is altered in pPROM patients, with a lower Systemic Vascular Resistance and higher Cardiac Output vs. controls. This hyperdynamic circulation appears to anticipates the changes of serum markers of inflammation (CRP, WBC count) and seems to be more pronounced at admission in pPROM patients developing unfavorable outcomes.

We aimed at analyzing the relationship between maternal hemodynamics as expressed by Peripheral Vascular Resistance (PVR) at mid gestation and fetal growth at delivery in chronic hypertension. 152 chronic hypertensive patients were submitted to echocardiography noting PVR at 22-24 weeks' gestation and were followed until delivery noting birthweight centile and the diagnosis of fetal growth restriction (FGR). The logarithmic correlation analysis showed that PVR at mid gestation was strongly related to birthweight at delivery (

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.

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 0.001). CI is significantly lower in GDM women already at the first evaluation (p = 0.002), whereas TVR and PKR were significantly higher in GDM (p 0.001). GDM women showed also lower INO values than controls in all assessments.A hemodynamic maternal maladaptation to pregnancy can be detected in GDM women. The effect of hyperglycemia on vascular system or a poor pre-pregnancy cardiovascular (CV) reserve could explain this hemodynamic maladaptation. The abnormal CV response to pregnancy in GDM women may reveal a predisposition to develop CV disease later in life and might help in identifying patients who need a CV follow-up.

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 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

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

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

Cardiac output rises in pregnancy, and most of this increase occurs in the first trimester. Both heart rate and stroke volume contribute to this increase, which, coupled with a decrease in mean arterial pressure, determines a reduction of maternal total vascular resistance (TVR) in physiological pregnancy. The absence of a ‚correct’ maternal cardiovascular compensatory response (absence of increase in cardiac output, heart rate, stroke volume, left ventricular mass and decrease in maternal TVR), in addition to abnormal trophoblastic invasion, might be one of the factors that could determine a reduced placental perfusion and, eventually, the development of fetal intrauterine growth restriction (IUGR). In fact, pregnancies complicated by IUGR appear to lack the stimulus to induce the hemodynamic changes typically present in physiological pregnancy such as the increase in preload, maternal heart rate, stroke volume, the enlargement of the left atrium and, above all, the reduction of TVR. It is difficult to e...

may also impair fetal growth and perinatal health and outcomes [9]. The role of fertility drugs during in-vitro fertilization in the setting of Hypertension is less known. Concerning ongoing clinical experiences, pregnancy-induced hypertension was significantly higher in the patients developing ovarian hyperstimulation syndrome than group control [10]. In this setting, our study is ongoing to investigate the onset of cardiovascular disease in women in high-fertility drug treatment.

Objective To evaluate the prognostic impact of elevated total vascular resistance (TVR) on the outcome of pregnancy in early mild gestational hypertension (EMGH). Design Prospective observational study. Setting Data collected from women with EMGH referred to the obstetrics outpatient clinic of Tor Vergata University from June 2003 to June 2005. Population A total of 268 women with EMGH (systolic and diastolic blood pressure [BP] 140–150 mmHg and 90–99 mmHg, respectively, without significant proteinuria). Methods Women had a maternal echocardiographic examination and BP examination within 24 hours of diagnosis. From this, the TVR was calculated and the geometric pattern of the left ventricle assessed. Main outcome measures Fetal/maternal adverse outcomes (pre-eclampsia, preterm delivery, placental abruption, other maternal medical problems, fetal distress, neonatal low birthweight, admittance to neonatal intensive care unit and perinatal death). Results Ninety-two out of the 268 pregnancies showed adverse outcomes (34.3%). The best independent predictor for the composite of maternal and fetal complications was TVR (OR 64.4, 95% CI 25.9–160.1). The cutoff value was 1340 dyn seconds/cm5 with a sensitivity and a specificity of 90 and 91%, respectively. Concentric geometry of the left ventricle was also an independent predictor (OR 4.72, 95% CI 1.85–12.04). Conclusions Echocardiography could help in identifying women with EMGH who subsequently develop maternal and fetal complications, allowing a classification in high-risk (TVR > 1340 dyn seconds/cm5, concentric geometry of the left ventricle) and low-risk women (TVR < 1340 dyn seconds/cm5, nonconcentric geometry of the left ventricle) for adverse outcomes of pregnancy.

Objective To determine reference values of fetal subcutaneous tissue thickness (SCTT) throughout gestation in a healthy population and to compare them with those from a population of pregnant women with gestational diabetes under standard therapy. Methods Three hundred and three women recruited from a high-risk pregnancy clinic were classified as being healthy (n = 218) or as having gestational diabetes (n = 85) on the basis of a negative or positive oral glucose tolerance test, respectively. They were enrolled into the cross-sectional study at 20 weeks' gestation. Ultrasound examinations were performed approximately every 3 weeks until delivery at term. The mid-arm fat mass and lean mass (MAFM, MALM), the mid-thigh fat mass and lean mass (MTFM, MTLM), the abdominal fat mass (AFM) and the subscapular fat mass (SSFM) were evaluated. Time-specific reference ranges were constructed from the 218 healthy women and a conventional Student's t-test was performed to compare SCTT values between the two study groups throughout gestation. Results Normal ranges, including 5th, 50th and 95th centiles of the distribution, were generated for each SCTT parameter obtained in each of the two groups of women. Significant differences were found between the two study groups at 37–40 weeks' gestation for MTFM, at 20–22 and 26–28 weeks for MTLM, at 31–34 and 35–37 weeks for MAFM, at 26–28 and 38–40 weeks for SSFM, and at 39–40 weeks for AFM, the mean residual values always being greater in gestational diabetic women than they were in the group of healthy pregnant women. Conclusions We provide gestational age-specific reference values for fetal SCTT. Fetal fat mass values, particularly in late gestation, are greater in women with gestational diabetes compared with healthy women. The reference values may have a role in assessing the influence of maternal metabolic control on fetal state. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.

Why should obstetricians study maternal cardiac function in normal and complicated pregnancies? Despite our understanding of the importance of disease processes, such as autoimmunity, impaired renal function and long-standing diabetes, on the placenta and thus pregnancy outcome, new data is emerging to suggest that early central cardiovascular adaptions are central to pregnancy success. Furthermore, successful maternal cardiovascular adaptions are a diagnostic test of longer-term cardiovascular health for the mother. The importance of the maternal ‘cardiac pump’ as the “core” of adaptation to pregnancy has increased in the last years. Studies identifying high risk patients by uterine artery Doppler waveforms in the 2nd trimester indicate that high uterine vascular impedance affects a proportion of women (resulting in severe preeclampsia) while the majority remain well. This dichotomy in maternal response is one explanation for the poor screening characteristics of uterine artery Doppler in unselected women. Women destined to develop preeclampsia with abnormal uterine artery Doppler have a latent period before the disease develops. During this phase, the heart adapts to alterations in circulating blood volume, placental implantation, and maternal peripheral vascular impedance. We believe that disordered heart function is an unavoidable part of the disease spectrum of preeclampsia, since it makes many adaptions even in the face of normal pregnancy. In this article we summarise the experience of our group and the published literature concerning maternal cardiac performance in normal and complicated pregnancies. These findings are relevant to modern day clinical practice.

The recent efforts in the study of fetal compartments could help us to a better recognition of the proper fetal growth and well being. Fat content correlates directly with energy stores. Fat mass and lean body mass is often used in the nutritional assessment of the individual. Moreover chromosomal abnormalities may be detected by studying the fetal soft tissues of the neck, thus providing further proofs of the importance of evaluating the fetal body compartments. To obtain fat mass and lean mass, several measurements were proposed. We report a review of the literature on that topic.

To evaluate the differences and similarities in diastolic function and left ventricular geometry in gestational and essential hypertension.Thirty-nine consecutive gestational hypertensive pregnant women in the third trimester of gestation (GH), 40 nonpregnant essential hypertensive women (EH), and 38 normotensive nonpregnant women (N) matched for age were enrolled into the study and underwent echocardiographic and Doppler evaluations. The GH and EH patients were evaluated prior to the administration of any drug treatment.Left atrial function was similar in GH and N subjects and lower than that in EH patients. Both GH and EH patients had early left ventricular diastolic filling pattern significantly different as compared to N subjects (longer isovolumetric relaxation time, deceleration time of the E wave, and lower E wave velocity in GH and EH vs. N), whereas the late filling properties were similar in GH and N subjects with a lower A velocity, and velocity-time integral vs. EH (p0.05). Systolic fraction of the pulmonary vein flow was similar in GH and EH patients and lower in N subjects. Altered left ventricular geometry was more common in GH than in EH, whereas normotensive subjects did not show any alteration of the geometric pattern.Gestational and essential hypertension induce similar early altered diastolic filling of the left ventricle. Essential hypertension is characterized by a compensatory late filling mechanism due to an enhancement of left atrial function. Gestational hypertension is characterized by altered left ventricular geometry, which is far less common during essential hypertension.

Human reproduction is a rather inefficient process, yet the molecular reasons for this inefficiency remain unknown. IVF and embryo transfer (IVF-embryo transfer) also results in a high frequency of implantation failures and early spontaneous abortions. Here we show that the anandamide (AEA)-degrading enzyme, fatty acid amide hydrolase (FAAH), had significantly lower activity (46 +/- 17 versus 161 +/- 74 pmol/min per mg protein) and protein content (0.10 +/- 0.03 versus 0.23 +/- 0.06 units) in lymphocytes of IVF-embryo transfer patients who failed to achieve an ongoing pregnancy than in those who become pregnant, and this was paralleled by a significant increase in blood AEA (4.0 +/- 2.2 pmol/ml and 0.9 +/- 1.0 pmol/ml respectively). The blood levels of the other endocannabinoid, 2-arachidonoylglycerol, or of the AEA congener, N-palmitoylethanolamine, which are metabolized by enzymes different from FAAH, was not different between the pregnant and nonpregnant women, nor was there any difference in the activity of the AEA membrane transporter or the amounts of cannabinoid receptors in lymphocytes. Taken together with the reported negative effects of AEA on embryo implantation, this study indicates that low FAAH activity and subsequent increased AEA levels in blood might be one of the causes of implantation failure or pregnancy loss, thereby leading to a better understanding of the pathophysiological and therapeutic implications of endocannabinoids in human fertility.

To evaluate pregnancy, delivery and neonatal outcome in singleton primiparous versus multiparous women with/without endometriosis.Multicentric, observational and cohort study on a group of Caucasian pregnant women (n = 2239) interviewed during their hospitalization for delivery in five Italian Gynecologic and Obstetric Units (Siena, Rome, Padua, Varese and Florence).Primiparous women with endometriosis (n = 219) showed significantly higher risk of small for gestational age fetuses (OR: 2.72, 95% CI 1.46-5.06), gestational diabetes (OR: 2.13, 95% CI 1.32-3.44), preterm premature rupture of membranes (OR: 2.93, 95% CI 1.24-6.87) and preterm birth (OR: 2.24, 95% CI 1.46-3.44), and were hospitalized for a longer period of time (p 0.0001) comparing with control group (n = 1331). Multiparous women with endometriosis (n = 97) delivered significantly more often small for gestational age fetuses (OR: 2.93, 95% CI 1.28-6.67) than control group (n = 592). Newborns of primiparous women with endometriosis needed more frequently intensive care (p = 0.05) and were hospitalized for a longer period of time (p 0.0001).Women with endometriosis at first pregnancy have an increased risk of impaired obstetric outcome, while a reduced number of complications occur in the successive gestation. Therefore, it is worthy for obstetricians to increase the surveillance in nulliparous women with endometriosis during pregnancy.

BACKGROUND: Implantation and early embryo development are finely regulated processes in which several molecules are involved. Evidence that thyroid hormones (TH: T4 and T3) might be part of this machinery is emerging. An increased demand for TH occurs during gestation, and any alteration in maternal thyroid physiology has significant implications for both maternal and fetal health. Not only overt but also subclinical hypothyroidism is associated with infertility as well as with obstetric complications, including disruptions and disorders of pregnancy, labor, delivery, and troubles in early neonatal life. METHODS: We searched the PubMed and Google Scholar databases for articles related to TH action on ovary, endometrium, trophoblast maturation and embryo implantation. In addition, articles on the regulation of TH activity at cellular level have been reviewed. The findings are hereby summarized and critically discussed. RESULTS: TH have been shown to influence endometrial, ovarian and placental physiology. TH receptors (TR) and thyrotropin (thyroid-stimulating hormone: TSH) receptors (TSHR) are widely expressed in the feto-maternal unit during implantation, and both the endometrium and the trophoblast might be influenced by TH either directly or through TH effects on the synthesis and activity of implantation-mediating molecules. Interestingly, due to the multiplicity of mechanisms involved in TH action (e.g. differential expression of TR isoforms, heterodimeric receptor partners, interacting cellular proteins, and regulating enzymes), the TH concentration in blood is not always predictive of their cellular availability and activity at both genomic and nongenomic level. CONCLUSIONS: In addition to the known role of TH on the hormonal milieu of the ovarian follicle cycle, which is essential for a woman's fertility, evidence is emerging on the importance of TH signaling during implantation and early pregnancy. Based on recent observations, a local action of TH on female reproductive organs and the embryo during implantation appears to be crucial for a successful pregnancy. Furthermore, an imbalance in the spatio-temporal expression of factors involved in TH activity might induce early arrest of pregnancy in women considered as euthyroid, based on their hormonal blood concentration. In conclusion, alterations of the highly regulated local activity of TH may play a crucial, previously underestimated, role in early pregnancy and pregnancy loss. Further studies elucidating this topic should be encouraged.

Background Umbilical cord blood (UCB) is an important source of hematopoietic stem cells (HSCs). However, the concentration of cells in cord blood units is limited and this may represent the main restriction to their therapeutic clinical use. The percentage of metabolically active stem cells provides a measure of the viability of cells in an UCB sample. It follows that an active cellular metabolism causes a proliferation in stem cells, offering an opportunity to increase the cellular concentration. A high cell dose is essential when transplanting cord stem cells, guaranteeing, in the receiving patient, a successful outcome. This study is designed to evaluate the impact of docosahexaenoic acid (DHA) supplementation in pregnant women, in order to increase the quantity and viability of the cells in UCB samples. Methods/design The metabolic demand of DHA increases in the course of pregnancy and reaches maximum absorption during the third trimester of pregnancy. According to these observations, this trial will be divided into two different experimental groups: in the first group, participants will be enrolled from the 20th week of estimated stage of gestation, before the maximum absorption of DHA; while in the second group, enrolment will start from the 28th week of estimated stage of gestation, when the DHA request is higher. Participants in the trial will be divided and randomly assigned to the placebo group or to the experimental group. Each participant will receive a complete set of capsules of either placebo (250 mg of olive oil) or DHA (250 mg), to take one a day from the 20th or from the 28th week, up to the 40th week of estimated gestational age. Samples of venous blood will be taken from all participants before taking placebo or DHA, at the 20th or at the 28th week, and at the 37th to 38th week of pregnancy to monitor the level of DHA. Cell number and cellular viability will be evaluated by flow cytometry within 48 hours of the UCB sample collection. Trial registration International Standard Randomised Controlled Trial Number Register: ISRCTN58396079. Registration date: 8 October 2013.

Objective To study second-trimester maternal cardiac adaptation in asymptomatic patients at risk, on the basis of abnormal uterine artery Doppler, for the development of gestational hypertension or having a small-for-gestational age fetus. Fetal and maternal outcomes were verified at the end of pregnancy. Methods Thirty-six normotensive women with abnormal uterine artery waveforms underwent maternal echocardiographic examination at 24 weeks' gestation. Results Twenty-one women (58.3%) subsequently showed normal outcome; 12 patients developed gestational hypertension (33.3%) and three (8.3%) had small-for-gestational age newborns. Left ventricular outflow tract, left ventricular diastolic dimensions and atrial and ventricular function were significantly lower in the pathological outcome group. Diastolic function parameters were significantly different between the two groups: peak mitral E-wave and A-wave and A-wave duration showed lower values in the pathological outcome group. Isovolumetric relaxation time of the left ventricle was significantly longer in the pathological outcome group. The prevalence of an altered geometric pattern was 14.3% (3/21) in the normal and 80% (12/15) in the pathological outcome groups (P < 0.001). Conclusions Women who subsequently develop a complication of pregnancy tend to display abnormal cardiac adaptation. An abnormal placentation process, expressed by an elevated resistance index and the presence of notches in the uterine artery waveform, are likely to cause an adaptative mechanism involving the whole cardiovascular system. A pathological outcome of pregnancy is associated with the failure of this process. Copyright © 2001 International Society of Ultrasound in Obstetrics and Gynecology