Circulating EGFL7 distinguishes between IUGR and PE: an observational case–control study

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

Fetal brain hemodynamics in pregnancies at term: correlation with gestational age, birthweight and clinical outcome

Introduction: The primary aim of this study was to ascertain the strength of association between cerebral blood flow assessed in anterior (ACA), middle (MCA), and posterior (PCA) cerebral arteries and the following clinical outcomes: small for gestational age (SGA), induction of labor (IOL) for oligohydramnios and caesarean section (CS) for nonreassuring fetal status (NRFS) during labor. Material and methods: Retrospective analysis of prospectively collected data on consecutive singleton pregnancies from 40 0/7 to 41 6/7 week of gestation. UA, ACA, MCA, PCA pulsatility index (PI) were measured from 40 weeks of gestations. Furthermore, the ratios between cerebral blood flow and UA (CPR, ACA/UA and PCA/UA) were calculated and correlated with the observed outcomes. Results: Two hundred twenty-four singleton pregnancies were included in the study. Mean PI of either ACA (p = .04), MCA (p = .008), and PCA (p = .003) were lower in the SGA compared to non-SGA group; furthermore, mean PCA PI was significantly lower than MCA PI (p = .04). Furthermore, CPR (p = .016), ACA/UA (p = .02), and PCA/UA (p = .003) were significantly lower in the SGA group compared to controls. UA, ACA, MCA, and PCA PI were higher in women undergoing IOL for oligohydramnios compared to controls. Logistic regression analysis showed that CPR and PCA/UA ratio were independently associated with SGA. SGA, ACA PI, and ACA/UA were independently associated with CS for NRFS. Finally, birthweight centile, were independently associated with IOL oligohydramnios. Despite this, the predictive accuracy of Doppler in detecting any of the explored outcome was only poor to moderate. Conclusion: Redistribution of cerebral blood flow at term is significantly associated with SGA, IOL for oligohydramnios and CS for NRFS in labor. However, the predictive accuracy of Doppler at term is only poor to moderate, thus advising against its use in clinical practice as a standalone screening test for adverse perinatal outcome in pregnancies at term. Key Message Redistribution of cerebral blood flow at term is significantly associated with SGA, IOL for oligohydramnios and CS for NRFS in labor

PTH-rP and PTH-R1 Expression in Placentas from Pregnancies Complicated by Gestational Diabetes: New Insights into the Pathophysiology of Hyperglycemia in Pregnancy

Background: this study investigated the expression of parathyroid hormone-related protein (PTH-rP) and PTH/PTH-rP receptor PTH-R1 in placentas from women with gestational DM (GDM), and the relationship between PTH-R1 and PTH-rP expression and pregnancy characteristics. Methods: we prospectively enrolled 78 pregnant women with GDM, and immunochemistry for PTH-rP and PTH-R1 was performed on placentas. Patients were grouped according to the positivity of PTH-R1 or PTH-rP expression, and pregnancy characteristics were compared between the two groups. Results: PTH-rP and PTH-R1 expression were highest in the extravillous cytotrophoblast and in the decidua. In extravillous cytotrophoblast, PTH-rP expression was higher in women with abnormal at fasting glycemia compared to women with abnormal 60' or 120' glycemia (25/25, 50% vs. 6/28, 21.4%, χ2 = 6.12, p = 0.01), and PTH-R1 expression was higher in women with abnormal oral glucose tolerance test (OGTT) at fasting glycemia compared to women with abnormal 60' or 120' glycemia (37/50, 74% vs. 15/28, 53.6%, χ2 = 3.37, p = 0.06). In syncytiotrophoblast, PTH-rP-positive placentas were characterized by higher incidence of 1 min Apgar score < 7 (2/9, 22.2% vs. 2/69, 2.9%, χ2 = 6.11, p = 0.01) and maternal obesity (4/9, 44.4% vs. 11/69, 16.7%, χ2 = 3.81, p = 0.05). Conclusion: placental PTH-rP and PTH-R1 expression is dependent on the type of maternal hyperglycemia, and it is associated with adverse pregnancy outcomes

CIRCULATING PLACENTAL VESCICLES CARRY HLA-DR IN PRE - ECLAMPSIA : A NEW POTENTIAL MARKER OF THE SYNDROME

Pre-eclampsia (PE) is a common disorder of pregnancy that usually presents with hypertension and proteinuria. The clinical presentation arises from soluble factors released into the maternal circulation from the placenta owing to the stress of syncytiotrophoblast, consequence of defective placentation occurring in the first half of pregnancy. Reduced tolerance of the semiallogeneic fetus by the maternal immune system has been proposed as first trigger leading to poor placentation. We previously observed aberrant expression of human leukocyte antigen (HLA)-DR molecules in the syncytiotrophoblast of a subset of women with PE. Aim of this study was to investigate abnormal expression of circulating HLA-DR in syncytiotrophoblast-derived extracellular vesicles (STBEVs) in women with PE compared to normal pregnant women

Local representative democracy and protest politics:the case of the Five-star Movement

In recent years, protest politics has become a relevant phenomenon in various European countries. Italy has witnessed the rise of the Five-star Movement (M5S), an anti-establishment party, which, at the 2013 general election, obtained one-fourth of the total votes. However, the story of this ‘party-movement’ started at the local level, as a civic network aimed at changing administrative practices in municipal government. By using an original dataset on representation in 671 Italian municipalities from 2010 to 2014, this article aims to explain not only the subnational political success of the M5S but also the challenges and contradictions that a newly formed movement faces in multi-level electoral arenas

Contrast Agents during Pregnancy: Pros and Cons When Really Needed

Many clinical conditions require radiological diagnostic exams based on the emission of different kinds of energy and the use of contrast agents, such as computerized tomography (CT), positron emission tomography (PET), magnetic resonance (MR), ultrasound (US), and X-ray imaging. Pregnant patients who should be submitted for diagnostic examinations with contrast agents represent a group of patients with whom it is necessary to consider both maternal and fetal effects. Radiological examinations use different types of contrast media, the most used and studied are represented by iodinate contrast agents, gadolinium, fluorodeoxyglucose, gastrographin, bariumsulfate, and nanobubbles used in contrast-enhanced ultrasound (CEUS). The present paper reports the available data about each contrast agent and its effect related to the mother and fetus. This review aims to clarify the clinical practices to follow in cases where a radiodiagnostic examination with a contrast medium is indicated to be performed on a pregnant patient

Continuous Glucose Monitoring in Women with Normal OGTT in Pregnancy

Continuous glucose monitoring (CGM) might be an effective tool to improve glycemic control in gestational diabetes mellitus (GDM). Few data are available about its utilization as a diagnostic tool to find potential alterations of glycemia in subjects with normal oral glucose tolerance test (OGTT). In this preliminary prospective real-life observational study, we aimed to analyze the glycemic pattern in normal and gestational diabetes mellitus (GDM) women by continuous glucose monitoring (CGM) in order to detect potential differences between the two groups and glycemic alterations despite a normal OGTT. After the screening for GDM, subjects were connected to a CGM system for seven consecutive days. The areas under the curve of the first 60 minutes after each meal and 60 minutes before breakfast were analyzed. Women with normal OGTT that during CGM showed impaired glycemic values (more than 95 fasting or more than 140 one hour after meals or more than 120 two hours after meals) performed one week of self-monitoring of blood glucose (SMBG). After OGTT, 53 women considered normal and 46 affected by GDM were included. CGM parameters did not show any differences between the two groups with impaired glycemic excursions found in both groups. After CGM period, 33 women with normal OGTT showed abnormal glycemic patterns. These 33 women then performed one week of SMBG. After evaluation of one week of SMBG, 21 required diet therapy and 12 required insulin treatment and were followed until the delivery. An increase in gestational weight gain was observed in normal women with normal OGTT but this was not significant. No significant data were found regarding neonatal outcomes in the two groups of women. In conclusion, CGM use in pregnancy might help to detect glycemic fluctuations in women with normal OGTT, improving their treatment and outcomes

In vitro human growth hormone increases human chorionic gonadotropin and progesterone secretion by human placenta at term: evidence of a modulatory role by opioids

We examined the in vitro effect of human growth hormone (hGH) on hormone placental production and the modulation by opioids of this function. Small placental fragments from 12 term placentas were incubated at 37 degrees C in a 95% air and 5% CO2 atmosphere for 4 h with various concentrations of hGH (1-1000 ng/ml) or naloxone (3-500 ng/ml). Both hGH and naloxone increased the concentrations of human chorionic gonadotropin (hCG) and progesterone in the media. The effect of the hGH was dose-dependent and statistically significant at 10 ng/ml, while naloxone was able to increase hCG and progesterone production only at the highest doses (250-500 ng/ml). The concomitant treatment with ineffective doses of naloxone and hGH was able to enhance hCG and progesterone secretion reaching levels similar to those obtained with the highest doses of hGH alone. High naloxone concentrations significantly decreased both hCG and progesterone secretion induced by high doses of hGH. This study confirms the relevance of growth hormone in sustaining placental endocrine activities and indicates an effect of opioids in modulating these function

Testing an Emerging Paradigm in Migration Ecology Shows Surprising Differences in Efficiency between Flight Modes

To maximize fitness, flying animals should maximize flight speed while minimizing energetic expenditure. Soaring speeds of large-bodied birds are determined by flight routes and tradeoffs between minimizing time and energetic costs. Large raptors migrating in eastern North America predominantly glide between thermals that provide lift or soar along slopes or ridgelines using orographic lift (slope soaring). It is usually assumed that slope soaring is faster than thermal gliding because forward progress is constant compared to interrupted progress when birds pause to regain altitude in thermals. We tested this slope-soaring hypothesis using high-frequency GPS-GSM telemetry devices to track golden eagles during northbound migration. In contrast to expectations, flight speed was slower when slope soaring and eagles also were diverted from their migratory path, incurring possible energetic costs and reducing speed of progress towards a migratory endpoint. When gliding between thermals, eagles stayed on track and fast gliding speeds compensated for lack of progress during thermal soaring. When thermals were not available, eagles minimized migration time, not energy, by choosing energetically expensive slope soaring instead of waiting for thermals to develop. Sites suited to slope soaring include ridges preferred for wind-energy generation, thus avian risk of collision with wind turbines is associated with evolutionary trade-offs required to maximize fitness of time-minimizing migratory raptors