A case series of chorioangiomas in placentas with clinical indication for histological examination.

Chorioangiomas are benign angiomas arising from chorionic tissue and they are the most common non-trophoblastic tumors of the placenta, as they are observed in 1% of all placentas examined. Most chorioangiomas are small and asymptomatic, often undetected during a prenatal ultrasound, and their clinical significance is still unknown. Large chorioangiomas, measuring more than 4-5 cm in diameter, can usually be detected prenatally by gray-scale or color Doppler sonography, and may be associated with maternal or fetal complications, such as preeclampsia, maternal mirror syndrome, preterm delivery, nonimmune fetal hydrops, fetal growth restriction and fetal demise. We herein describe the clinical-pathological features of a monocentric series of 30 placental chorioangiomas and discuss their clinical-pathological features and possible molecular mechanisms underlying their development.

Changes in cytokine and sequestosome-1 levels during twin pregnancy progression: Association with outcome.

BACKGROUND: Twin pregnancies are associated with complications and adverse outcomes. The number of twin pregnancies has increased in the last decades, due to the use of assisted reproductive techniques and delayed childbearing. Analysis of changes that occur during twin pregnancy progression and their association with outcome will lead to improved clinical interventions. OBJECTIVE: We evaluated if the plasma concentration of select cytokines and the level of sequestosome-1 (p62) in peripheral blood mononuclear cells (PBMCs) during each trimester of twin gestations was predictive of pregnancy outcome. STUDY DESIGN: This prospective, observational study was conducted at Careggi University Hospital, Florence, Italy. Plasma from 82 women with twin pregnancies was collected in each trimester for measurement of interleukin (IL)-1ß, IL-6, IL-10, IL-12 and tumor necrosis factor (TNF)-α. The intracellular PBMC concentration of p62, a protein involved in autophagy, kinase activity and cell differentiation, was also determined. RESULTS: IL-1ß (p < 0.001), IL-6 (p < 0.001), TNF-α (p < 0.001) and p62 (p < 0.05) increased from the 1st to the 2nd to the 3rd trimester. The TNF-α level was correlated with the IL-1ß concentration in the 1st and 3rd trimesters p < 0.01) and with the IL-6 concentration in each of the three trimesters (p < 0.01). The intracellular p62 level in PBMCs was negatively correlated with the concentration of IL-1ß in the 2nd trimester (p < 0.05) and negatively correlated with the IL-6 level in the 3rd trimester (p < 0.05). The TNF-α level was significantly higher in the 2nd (p < 0.05) and 3rd (p < 0.001) trimester in women with a spontaneous preterm delivery. The TNF-α concentrations in the 2nd (p < 0.05) and 3rd (p < 0.01) trimester, respectively, and 3rd trimester IL-6 (p < 0.01), were negatively associated with gestational age at delivery. The concentration of IL-6 was highest in the 2nd (p < 0.05) and 3rd (p < 0.05) trimesters in women who utilized assisted reproductive technologies. An elevated IL-1ß level in the 3rd trimester was associated with gestational diabetes mellitus (p < 0.05). CONCLUSION: Variations in cytokine levels between individual women during the three trimesters of twin gestations are predictive of spontaneous preterm delivery and the onset of gestational diabetes.

Antepartum unscarred uterine rupture caused by placenta percreta: a case report and literature review.

The main risk for uterine rupture is the presence of a uterine scar due to prior cesarean delivery or other uterine surgery. However, rupture in an unscarred uterus is extremely rare, and risk factors include multiple gestations, trauma, congenital anomalies, use of uterotonics and placenta accreta spectrum.Placenta accreta spectrum, also known as morbidly adherent placenta, is becoming increasingly common and is associated with significant maternal and neonatal morbidity and mortality.We report a case of unscarred uterine rupture due to placenta percreta in a multiparous woman that required emergency peripartum hysterectomy.

Tryptophan degradation enzymes and Angiotensin (1-7) expression in human placenta.

Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are key enzymes for tryptophan degradation, regulating immune tolerance during pregnancy. The intrauterine renin-angiotensin system is also involved in the progression of a healthy pregnancy. Angiotensin(1-7) maintains the integrity of fetal membranes via counteracting the pro-inflammatory actions of Angiotensin II. No data are available on placental Angiotensin(1-7) co-expression with TDO. We aimed to characterize TDO mRNA expression and its localization in different areas of the placenta of physiological pregnancies delivered at term; its co-expression with Angiotensin(1-7) and its correlation with the plasma kynurenine/tryptophan (Kyn/Trp) ratio was investigated. This prospective observational study included a nonconsecutive series of 20 singleton uncomplicated pregnancies delivered vaginally. TDO mRNA was expressed in both maternal and fetal sides of the placentas and TDO protein also in the villi and it was co-expressed with IDO1 in almost half of the placental cells at these sites. The percentage of TDO+ and IDO1+ cells appeared to be influenced by maternal pre-gestational smoking and newborn weight. A strong correlation was found between the percentage of TDO+ and IDO1+ cells in the villi. TDO+ cells also expressed Angiotensin(1-7), with a higher percentage on the fetal side and in the villi compared to the maternal one. Kyn/Trp plasma ratio was not correlated with IDO and TDO expression nor with the patient's characteristics. Collectively, our data indicate that TDO is detectable in placental tissue and is co-expressed with IDO and with Angiotensin(1-7)+ on the fetal side and in the villi.

A comparison of first trimester blood pressures obtained at the time of first trimester pre-eclampsia screening and those obtained during prenatal care visits.

OBJECTIVE: To determine if enrollment blood pressures in a study on first trimester preeclampsia prediction significantly differed from those obtained during routine prenatal care visits in the first trimester. STUDY DESIGN: Women carrying a singleton gestation were prospectively enrolled in a first trimester study on preeclampsia prediction, and had systolic and diastolic blood pressure (SBP, DBP) measured at the time of enrollment. Blood pressure was also measured with the same technique by clinic nurses during the routine prenatal visits throughout the first trimester of pregnancy (9-14 weeks). The enrollment-BP (E-BP) and average first trimester-BP (aFT-BP) were compared using a paired samples t-test or Wilcoxon test, as appropriate. Smokers and patients on antihypertensive medications were excluded from the analysis. test. RESULTS: 644 women had prenatal care in the primary study center and met study criteria. The mean gestational age at study enrollment was 12.5 weeks. No significant difference was found between E-SBP and aFT-SBP (p = 0.10). Enrollment DBP and mean arterial pressure (MAP) were significantly lower than the aFT- DBP and -MAP (median DPB 67 vs 70 mm Hg and median MAP 83.7 vs 85 mmHg, respectively, p < 0.001). However, the difference was not clinically relevant (3 mmHg for DBP, and 1.3 mmHg for MAP). CONCLUSIONS: Blood pressures obtained in a setting of preeclampsia screening are not higher than those obtained during regular prenatal care in the first trimester. This suggests that the setting in which pre-eclampsia screening is performed is unlikely to be a confounder for blood pressure measurements and the risk assessment.

TRPA1 mediates the antinociceptive properties of the constituent of Crocus sativus L., safranal.

Safranal, contained in Crocus sativus L., exerts anti-inflammatory and analgesic effects. However, the underlying mechanisms for such effects are poorly understood. We explored whether safranal targets the transient receptor potential ankyrin 1 (TRPA1) channel, which in nociceptors mediates pain signals. Safranal by binding to specific cysteine/lysine residues, stimulates TRPA1, but not the TRP vanilloid 1 and 4 channels (TRPV1 and TRPV4), evoking calcium responses and currents in human cells and rat and mouse dorsal root ganglion (DRG) neurons. Genetic deletion or pharmacological blockade of TRPA1 attenuated safranal-evoked release of calcitonin gene-related peptide (CGRP) from rat and mouse dorsal spinal cord, and acute nociception in mice. Safranal contracted rat urinary bladder isolated strips in a TRPA1-dependent manner, behaving as a partial agonist. After exposure to safranal the ability of allyl isothiocyanate (TRPA1 agonist), but not that of capsaicin (TRPV1 agonist) or GSK1016790A (TRPV4 agonist), to evoke currents in DRG neurons, contraction of urinary bladder strips and CGRP release from spinal cord slices in rats, and acute nociception in mice underwent desensitization. As previously shown for other herbal extracts, including petasites or parthenolide, safranal might exert analgesic properties by partial agonism and selective desensitization of the TRPA1 channel.

Errors and pitfalls in reading the cardiotocographic tracing.

Reading of fetal heart rate (FHR) tracing during labor remains one of the most controversial and problematic issues in Obstetrics. The incorrect interpretation of CTG can be due to errors and pitfalls. Some common errors are related to the incorrect use of oxytocin, specifically the failure to recognize tachysystole, to correct it and to use oxytocin to accelerate labor when the fetal heart rate tracing is not reassuring. A common error is also the incorrect interpretation of deceleration that leads to unnecessary and often dangerous interventions, despite the clarification of the significance of decelerations, which in themselves are not a sign of impending acidosis, except when they are accompanied by loss of variability. Another potential error that can be identified as a pitfall is the transition from fetal to maternal heart rate (MHR) recording. The misidentification of MHR as FHR can potentially mask pathological FHR traces, appearing as a falsely reassuring trace.

Fetoscopic tracheal occlusion for treatment of non-isolated congenital diaphragmatic hernia.

Fetoscopic endotracheal occlusion (FETO) is a prenatal treatment that may increase survival in severe congenital diaphragmatic hernia (CDH). In the USA, FETO is offered for isolated severe left-sided CDH in the context of an FDA-approved feasibility study. FETO in non-isolated cases of severe CDH is only performed with a compassionate use exemption from US regulatory bodies. Anomalies frequently associated with CDH include congenital cystic lesions of the lung and cardiac defects. We describe two cases of non-isolated severe left-sided CDH that underwent prenatal FETO, survived after birth and underwent postnatal surgical repair. The potential benefit of FETO in this setting is discussed. © 2017 John Wiley & Sons, Ltd.

Relationship between first-trimester serum placental protein-13 and maternal characteristics, placental Doppler studies and pregnancy outcome.

OBJECTIVE: To examine potential correlations between maternal serum placental protein-13 (PP-13) and first trimester maternal and placental factors, and to evaluate the association of this marker with adverse pregnancy outcome. METHODS: Serum samples from prospectively enrolled patients between 11 and 13 weeks and 6 days were analyzed for PP-13 using an ELISA assay. The relationships between maternal serum PP-13 levels and gestational age, maternal age, ethnicity, parity, smoking status, body mass index (BMI), mean arterial blood pressure, uterine and umbilical artery Doppler parameters were examined. The association between first-trimester PP-13 levels and subsequent pre-eclampsia and delivery of a small for gestational age (SGA) neonate was also investigated, after excluding patients who received aspirin. RESULTS: In 908 patients, PP-13 levels ranged from 8.0 to 537.5 pg/mL. A significant negative correlation was identified between PP13 and BMI (Spearman rho -0.20, P<0.0001). Smoking significantly decreased PP-13 (P<0.01). No relationship was identified with the other parameters. In a subgroup of 668 low-risk patients who did not receive aspirin, PP-13 levels were not associated with development of pre-eclampsia, SGA or the combination of them. CONCLUSION: First-trimester PP-13 levels are significantly correlated with BMI and smoking. These correlations appear independent of uterine and umbilical artery resistance. In low risk patients, PP-13 levels fail to predict the risk for pre-eclampsia or SGA.

Blood gas values in clamped and unclamped umbilical cord at birth.

AIM: To determine the reliability of the cord blood gas analysis on the unclamped cord compared to the standard technique of sampling on double clamped cord. STUDY DESIGN: Prospective observational study conducted on 46 singleton neonates vaginally delivered at term. Matched pairs of umbilical artery and vein blood samples were collected from unclamped cord within 90s after birth and from the same cord after clamping, with the clamping occurring immediately after the first blood collection. A blood gas analysis was performed on each collected sample. OUTCOME MEASURES: Arterial and venous blood samples were analyzed for pH, PO2, pCO2, SaO2, hemoglobin concentration (ctHb) and base excess (BE). The values were compared between the two groups (clamped vs unclamped) using a Wilcoxon test. RESULTS: No significant difference was found in pH, PO2, pCO2, SaO2 and ctHb values on arterial blood between unclamped and clamped cord. The only significant difference was related to BE (p<0.001). For the venous blood, the values of pH, PO2, pCO2 were comparable between unclamped and clamped cord, while the values of SaO2, ctHb and BE were significantly different (p<0.05). CONCLUSION: No significant difference was found in almost all the arterial blood gas parameters and in the main venous blood gas parameters between unclamped and clamped cord. Sampling of cord blood for gas analysis may be performed on the unclamped cord right after birth without reducing the accuracy of the analysis.

Second-trimester prediction of delivery of a small-for-gestational-age neonate: integrating sequential Doppler information, fetal biometry, and maternal characteristics.

OBJECTIVE: The aim of this study was to investigate the predictive accuracy of second-trimester ultrasound parameters, maternal characteristics, and sequential Doppler changes between first and second trimesters for the prediction of small-for-gestational-age (SGA) infants (birth weight < 10th percentile). METHODS: We conducted a prospective study of singleton pregnancies enrolled in the first trimester with subsequent second-trimester follow-up. Maternal characteristics, uterine artery (UtA) pulsatility index (PI), fetal biometry, and umbilical artery (UA)-PI were ascertained. UtA and UA-PI change from first to second trimester was calculated (ΔUtA-PI and ΔUA-PI). These parameters were tested for their ability to predict delivery of an SGA infant. RESULTS: Among 1982 women, 172 delivered an SGA neonate. African-American ethnicity, nulliparity, tobacco use, and low abdominal circumference (AC) z-score were independent predictors of SGA. No difference was found in the magnitude of ΔUtA-PI and ΔUA-PI between SGA and no-SGA. Receiver-operating characteristics curve analysis yielded an area under the curve of 0.700 for AC z-score. The combination of low AC and bilateral notching had high specificity (99%) but low sensitivity (7%) for SGA prediction. CONCLUSIONS: A small second-trimester fetal AC is a specific marker for SGA when found with bilateral UtA notching. Only a small proportion is predicted by the factors studied, suggesting a small contributory role or later evolution of SGA.

First-trimester prediction of small-for-gestational age neonates incorporating fetal Doppler parameters and maternal characteristics.

OBJECTIVE: First-trimester screening for subsequent delivery of a small-for-gestational-age (SGA) infant typically focuses on maternal risk factors and uterine artery (UtA) Doppler. Our aim is to test if incorporation of fetal umbilical artery (UA) and ductus venosus (DV) Doppler improves SGA prediction. STUDY DESIGN: Prospective screening study of singletons at 11-14 weeks. Maternal characteristics, serum concentrations of pregnancy-associated plasma protein-A (PAPP-A) and free ß-human chorionic gonadotropin are ascertained and UtA Doppler, UA, and DV Doppler studies are performed. These parameters are tested for their ability to predict subsequent delivery of a SGA infant. RESULTS: Among 2267 enrolled women, 191 (8.4%) deliver an SGA infant. At univariate analysis women with SGA neonates are younger, more frequently African-American (AA), nulliparous, more likely to smoke, have lower PAPP-A and free ß-human chorionic gonadotropin levels. They have a higher incidence of UtA Doppler bilateral notching, higher mean UtA Doppler-pulsatility index z-scores (P < .001) and UA pulsatility index z-scores (P = .03), but no significant difference in DV-pulsatility index z-scores or in the incidence of abnormal qualitative UA and DV patterns. Multivariate logistic regression analysis identifies nulliparity and AA ethnicity (P < .001), PAPP-A multiple of the median and bilateral notching (P < .05) as determinants of SGA infant. Predictive sensitivity was low; receiver operating characteristic curve analysis yields areas under the curve of 0.592 (95% confidence interval, 0.548-0.635) for the combination of UtA Doppler and UA pulsatility index z-scores. CONCLUSION: Delivery of a SGA infant is most frequent in nulliparous women of AA ethnicity. Despite the statistical association with UtA Doppler first-trimester SGA prediction is poor and not improved by the incorporation of fetal Doppler.

Cell-free fetal DNA in maternal circulation after chorionic villous sampling.

OBJECTIVE: This study aims to estimate whether chorionic villous sampling (CVS) causes a significant increase of cell-free fetal DNA (cffDNA) in maternal circulation. METHOD: Fifty pregnant women with singleton pregnancy were recruited prior to CVS. Maternal peripheral blood was collected before and after CVS. A methylation-sensitive restriction enzyme digestion was used to select the placental-derived hypermethylated promoter of the RASSF1A gene in maternal plasma, thus differentiating cffDNA from mother's cell-free DNA (cfDNA), where the RASSF1A gene is normally hypomethylated. Total cfDNA and cffDNA amounts were compared before and after CVS in each patient. Data were compared using the Student t-test. RESULTS: No significant difference before and after CVS was found between the following: (i) total cfDNA concentration in plasma (p = 0.695); (ii) cffDNA concentration in plasma (p = 0.612); and (iii) percentage of fetal DNA in plasma (p = 0.835). After dividing the cases on the basis of the sex of the fetus, maternal age, gestational age, number of pregnancies, position of the placenta, and presence of trisomy of the fetus, no difference in fetal and total DNA concentrations before and after CVS was observed. CONCLUSION: The CVS does not seem to significantly disrupt the maternal-placental interface, as no significant increase of cffDNA in maternal plasma following CVS was observed.