Chronic Inflammation May Enhance Leiomyoma Development by the Involvement of Progenitor Cells.

Although the etiology of leiomyoma is unclear, a progenitor/undifferentiated cell population has been described whose dysregulation may be involved in the onset of uterine conditions. Moreover, inflammation is involved in the development of several tumors. The aim of this work was to understand if progenitor cells sustain a chronic inflammatory microenvironment that enhances leiomyoma development. Cells from 12 human leiomyoma and 12 normal myometrium samples of the same patients were in vitro isolated and exhaustively characterized (morphology, proliferation, cytofluorometry, differentiation, RT-PCR, immunofluorescence, immunohistochemistry, and Western blotting assays). Selected cytokines (ELISA) and inflammation-related genes (RT-PCR) were analyzed to identify healthy myometrium progenitor cells (MPCs) and leiomyoma progenitor cells (LPCs). Results show that (i) MPCs and LPCs share stemness features, such as immunophenotype and multidifferentiation assay, (ii) LPCs have a significantly shorter doubling time and a significantly higher expression of stemness genes (p < 0.05), and (iii) LPCs secreted significantly higher levels (p < 0.05) of cytokines related to chronic inflammation and significantly lower amounts (p < 0.05) of cytokines related to acute inflammation. Despite the limited sample size, comparisons between leiomyoma and normal myometrium tissue from each patient allowed normalization of patient-specific differences. The evidenced cytokine expression pattern related to chronic inflammation in LPCs may play a role in the increased risk of adverse obstetric outcomes (infertility, spontaneous miscarriage, and preterm birth) in women affected by leiomyomas. These women should be recognized as "high risk" and subjected to specialized management both before and during pregnancy.

Fetal Sex, Need for Insulin, and Perinatal Outcomes in Gestational Diabetes Mellitus: An Observational Cohort Study.

PURPOSE: This was a prospective observational cohort study that aimed to determine whether fetal sex influences the maternal and fetal outcomes of gestational diabetes mellitus (GDM). METHODS: In this study, 327 European primiparous women were consecutively recruited after diagnosis of GDM. AUC on the oral glucose tolerance test (OGTT), need for insulin therapy, maternal and obstetrical outcomes, and fetal fat mass (by measuring the thickness of the anterior abdominal subcutaneous tissue) were recorded and compared between the two subgroups of female and male fetuses. FINDINGS: Despite the absence of differences in multiple comparisons of the OGTT, the AUC-OGTT was significantly higher in women carrying a male fetus (22.6 [3.2] mmol/L vs 19.7 [2.8] mmol/L). The abdominal fat thickness appeared to increase with gestational age, with higher growth in male fetuses than in female fetuses. The overall risk of need for insulin therapy was significantly higher in women carrying a male fetus (odds ratio = 1.837). At delivery, birthweight was higher in males than in females only if adjusted for gestational age, similarly for placental weight, otherwise there were no significant differences between the groups in total length of gestation, rates of cesarean delivery, and Apgar scores. IMPLICATIONS: Overall, our data propose an association between fetal sex and GDM outcomes, suggesting the hypothesis that in maternal-fetal interactions, the fetus can affect maternal glucose metabolism.

Fetal Intra-abdominal Umbilical Vein Aneurysm.

IMPORTANCE: Fetal umbilical vein aneurysm is an uncommon anomaly that accounts for approximately 4% of umbilical cord abnormalities. The rate of intrauterine fetal death is reported to be approximately 4% to 5%, higher than the background rate of 0.7% that is generally reported during pregnancy. OBJECTIVE: The aim of this study was to review the pathophysiology, diagnosis, and clinical management of fetal umbilical vein aneurysm. EVIDENCE ACQUISITION: Advances in high-resolution ultrasound combined with color Doppler and 3-dimensional rendering have contributed to an increased understanding of the fetal venous circulation in recent years. RESULTS: When the diagnosis of umbilical vein aneurysm is made, the patient should undergo a detailed ultrasound evaluation of the fetal anatomy, including fetal echocardiography, to exclude associated anomalies. Amniocentesis should be offered when other anomalies are found. Patients should be informed about the potential for an unfavorable outcome of pregnancy and should undergo close ultrasound surveillance to assess the size of the aneurysm, as well as any evidence of thrombosis or signs of hydrops. CONCLUSIONS: The main prognostic feature associated with a poor outcome of umbilical vein aneurysm seems to be the presence of other anomalies. Early diagnosis is associated with a somewhat worse prognosis, and most fetal deaths have been observed between 27 and 30 weeks of gestation. In the third trimester, it is reasonable to perform serial ultrasound examinations to assess fetal growth, the size of the aneurysm, and the blood flow pattern within the aneurysm.

Growth factors and pathogenesis.

Growth factors are relatively small and stable, secreted or membrane-bound polypeptide ligands, which play an important role in proliferation, differentiation, angiogenesis, survival, inflammation, and tissue repair, or fibrosis. They exert multiple effects through the activation of signal transduction pathways by binding to their receptors on the surface of target cells. A number of studies have demonstrated the central role of growth factors and their signaling pathways in the pathogenesis of uterine leiomyomas. Numerous differentially expressed growth factors have been identified in leiomyoma and myometrial cells. These growth factors can activate multiple signaling pathways (Smad 2/3, ERK 1/2, PI3K, and ß-catenin) and regulate major cellular processes, including inflammation, proliferation, angiogenesis, and fibrosis which are linked to uterine leiomyoma development and growth. In this chapter, we discuss the role of growth factors and their signaling pathways in the pathogenesis of uterine leiomyomas.

Noninvasive fetal electrocardiography: an overview of the signal electrophysiological meaning, recording procedures, and processing techniques.

BACKGROUND: Noninvasive fetal electrocardiography (fECG), obtained positioning electrodes on the maternal abdomen, is important in safeguarding the life and the health of the unborn child. This study aims to provide a review of the state of the art of fECG, and includes a description of the parameters useful for fetus clinical evaluation; of the fECG recording procedures; and of the techniques to extract the fECG signal from the abdominal recordings. METHODS: The fetus clinical status is inferred by analyzing growth parameters, supraventricular arrhythmias, ST-segment variability, and fetal-movement parameters from the fECG signal. This can be extracted from an abdominal recording obtained using one of the following two electrode-types configurations: pure-abdominal and mixed. Differently from the former, the latter also provides pure maternal ECG tracings. From a mathematical point of view, the abdominal recording is a summation of three signal components: the fECG signal (i.e., the signal of interest to be extracted), the abdominal maternal ECG (amECG), and the noise. Automatic extraction of fECG includes noise removal by abdominal signal prefiltration (0.5-45 Hz bandpass filter) and amECG cancellation. CONCLUSIONS: Differences among methods rely on different techniques used to extract fECG. If pure abdominal electrode configurations are used, fECG is extracted directly from the abdominal recording using independent component analysis or template subtraction. Eventually, if mixed electrode configurations are used, the fECG can be extracted using the adaptive filtering fed with the maternal ECG recorded by the electrodes located in the woman thorax or shoulder.

The correlation between fetal bradycardia area in the second stage of labor and acidemia at birth.

OBJECTIVE: To quantify fetal bradycardia in the second stage of labor and to determine the threshold of the area that correlates with neonatal acidemia. METHOD: We analyzed the cardiotocograms of 33 women with single pregnancy and term spontaneous labor who presented fetal bradycardia in the second stage of labor. We retrospectively calculated the fetal bradycardia area in the last 60 min before delivery with an upper limit of 90 bpm and correlated the area with neonatal pH. The study of the regression line determined the cut-off threshold between fetal well-being and distress. Significance was set at p < 0.05. RESULTS: The linear correlation between the bradycardia area and neonatal pH indicate that increasing bradycardia area was correlated with significant pH decrease. The threshold value of the area indicative of severe acidemia was ≥ 12.72 cm(2) (Pearson r = -0.76, p < 0.002). The diagnostic accuracy of the test was 73%. The PPV = 78.5% and the NPV = 68.4%. With such a cut-off, the timing of acidemia can be calculated as 25 min for a fetal heart rate (FHR) of 80 bpm, 13 min for a FHR of 70 bpm, 8 min for a FHR of 60 bpm, 6 min for a FHR of 50 bpm and 5 min for a FHR of 40 bpm. CONCLUSION: The bradycardia area in the second stage of labor significantly correlates with an accurate timing of fetal acidemia. Regardless of the cause of the bradycardia, the time for intervention is often short, meaning that any available intervention may be ineffective in preventing acidemia or even injury.