Citral relaxes umbilical vessels of normotensive and preeclamptic parturients.

INTRODUCTION: Citral is a low-toxicity monoterpene that has a vasodilator effect on various smooth muscles, and The present study aimed to evaluate its vasorelaxant effect on umbilical vessels of normotensive parturients (NTP) and with preeclampsia parturients (PEP). METHOD: Segments of human umbilical artery (HUA) and vein (HUV) of NTP or PEP were mounted in a bath to record the force of contraction, under tension of 3.0 gf and contracted with the contracting agents: K+ (60 mM), 5 -HT (10 µM) and Ba2+ (1-30 mM). Next, the effect of citral (1-3000 µM) on these contractions and on basal tone was evaluated. RESULTS: In HUA and HUV, citral (1-1000 µM), in NTP condition, inhibited contractions evoked by K+ (IC50 of 413.5 and 271.3, respectively) and by 5-HT (IC50 of 164.8 and 574.3). In the PEP condition, in HUA and HUV, citral also inhibited the contractions evoked by K+ (IC50 of 363.3 and 218.3, respectively) and 5-HT (IC50 of 432.1 and 520.4). At a concentration of 1000 µM, citral completely or almost completely (>90 %) inhibited all contractions. At a concentration of 100-1000 µM, citral, in general, was already able to reduce the contraction induced by 1-3 mM Ba2+ in both AUH and VUH, under NTP and PEP conditions. DISCUSSION: Citral has been shown to be an effective HUA and HUV vasodilator in NTP and PEP. As its toxicity is low, it suggests that this substance can be considered a potential therapeutic agent.

Fetal hemodynamics and placental histopathology in Down syndrome.

OBJECTIVE: To evaluate the association between Doppler patterns in fetuses with Down syndrome (DS) and their placental histopathologic findings. METHODS: A retrospective cross-sectional study was performed by collecting data from medical records of singleton pregnancies between January 2014 and January 2022, whose fetuses had a confirmed diagnosis of DS either prenatally or postnatally. Placental histopathology, maternal characteristics, and prenatal ultrasound (biometric parameters and umbilical artery [UA] Doppler) were evaluated. RESULTS: Of 69 eligible pregnant women, 61 met the inclusion and exclusion criteria. In the sample, 15 fetuses had an estimated fetal weight < 10th percentile for gestational age (GA) and were considered small for gestational age (SGA). Thirty-eight fetuses had increased resistance on the UA Doppler. Histologic changes were detected in 100% of the placentas, the most common being delayed villous maturation, alterations associated with poor fetal vascular perfusion, and villous dysmorphism. More than 50% of the placentas showed alterations related to placental insufficiency. We did not observe a statistically significant association between UA Doppler examination and placental alterations. All placentas analyzed in the SGA subgroup showed findings compatible with placental insufficiency. CONCLUSION: We found no statistically significant association between placental histopathologic findings and UA Doppler abnormalities in fetuses with DS. The placental alterations identified were delayed villous maturation, alterations associated with poor fetal vascular perfusion, and villous dysmorphism.

Placental differences between severe fetal growth restriction and hypertensive disorders of pregnancy requiring early preterm delivery: morphometric analysis of the villous tree supported by artificial intelligence.

BACKGROUND: The great obstetrical syndromes of fetal growth restriction and hypertensive disorders of pregnancy can occur individually or be interrelated. Placental pathologic findings often overlap between these conditions, regardless of whether 1 or both diagnoses are present. Quantification of placental villous structures in each of these settings may identify distinct differences in developmental pathways. OBJECTIVE: This study aimed to determine how the quantity and surface area of placental villi and vessels differ between severe, early-onset fetal growth restriction with absent or reversed umbilical artery Doppler indices and hypertensive disorders of pregnancy or the 2 conditions combined among subjects with disease severity that warrant early preterm delivery. We hypothesized that the trajectories of placental morphogenesis diverge after a common initiating insult of deep defective placentation. Specifically, we postulated that only villi are affected in pregnancy-related hypertension, whereas both villous and vascular structures are proportionally diminished in severe fetal growth restriction with no additional effect when hypertension is concomitantly present. STUDY DESIGN: In this retrospective cohort study, paraffin-embedded placental tissue was obtained from 4 groups, namely (1) patients with severe fetal growth restriction with absent or reversed umbilical artery end-diastolic velocities and hypertensive disorders of pregnancy, (2) patients with severe fetal growth restriction with absent or reversed umbilical artery Doppler indices and no hypertension, (3) gestational age-matched, appropriately grown pregnancies with hypertensive disease, and (4) gestational age-matched, appropriately grown pregnancies without hypertension. Dual immunohistochemistry for cytokeratin-7 (trophoblast) and CD34 (endothelial cells) was performed, followed by artificial intelligence-driven morphometric analyses. The number of villi, total villous area, number of fetoplacental vessels, and total vascular area across villi within a uniform region of interest were quantified. Quantitative analyses of placental structures were modeled using linear regression. RESULTS: Placentas from pregnancies complicated by hypertensive disorders of pregnancy exhibited significantly fewer stem villi (-282 stem villi; 95% confidence interval, -467 to -98; P<.01), a smaller stem villous area (-4.3 mm2; 95% confidence interval, -7.3 to -1.2; P<.01), and fewer stem villous vessels (-4967 stem villous vessels; 95% confidence interval, -8501 to -1433; P<.01) with no difference in the total vascular area. In contrast, placental abnormalities in cases with severe growth restriction were limited to terminal villi with global decreases in the number of villi (-873 terminal villi; 95% confidence interval, -1501 to -246; P<.01), the villous area (-1.5 mm2; 95% confidence interval, -2.7 to -0.4; P<.01), the number of blood vessels (-5165 terminal villous vessels; 95% confidence interval, -8201 to -2128; P<.01), and the vascular area (-0.6 mm2; 95% confidence interval, -1.1 to -0.1; P=.02). The combination of hypertension and growth restriction had no additional effect beyond the individual impact of each state. CONCLUSION: Pregnancies complicated by hypertensive disorders of pregnancy exhibited defects in the stem villi only, whereas placental abnormalities in severely growth restricted pregnancies with absent or reversed umbilical artery end-diastolic velocities were limited to the terminal villi. There were no significant statistical interactions in the combination of growth restriction and hypertension, suggesting that distinct pathophysiological pathways downstream of the initial insult of defective placentation are involved in each entity and do not synergize to lead to more severe pathologic consequences. Delineating mechanisms that underly the divergence in placental development after a common inciting event of defective deep placentation may shed light on new targets for prevention or treatment.

Perillyl Alcohol Promotes Relaxation in Human Umbilical Artery.

BACKGROUND: Perillyl alcohol (POH) is a monoterpenoid found in plant essential oils and has been shown to relax murine vessels, but its effect on human vessels remains poorly studied. OBJECTIVE: The study aimed to characterize the effect of POH on human umbilical arteries (HUA). METHODS: Rings of HUA were obtained from uncomplicated patients and suspended in an organ bath for isometric recording. The vasorelaxant effect of POH in HUA was evaluated on basal tone and electromechanical or pharmacomechanical contractions, and possible mechanisms of action were also investigated. RESULTS: POH (1-1000 µM) altered the basal tone of HUA and completely relaxed HUA rings precontracted with KCl (60 mM) or 5-HT (10 µM), obtaining greater potency in the pharmacomechanical pathway (EC50 110.1 µM), suggesting a complex interference in the mobilization of extra- and intracellular Ca2+. POH (1000 µM) inhibited contractions induced by BaCl2 (0.1-30 mM) in a similar way to nifedipine (10 µM), indicating a possible blockade of L-type VOCC. In the presence of potassium channel blockers, tetraethylammonium (1 mM), 4-aminopyridine (1 mM), or glibenclamide (10 µM), an increase in the EC50 value of the POH was observed, suggesting a modulation of the activity of BKCa, KV, and KATP channels. CONCLUSION: The data from this study suggest that POH modulates Ca2+ and K+ ion channels to induce a relaxant response in HUA.

Incidence of congenital heart disease in fetuses diagnosed with single isolated umbilical artery. Systematic review and meta-analysis.

OBJECTIVE: To estimate the proportion of heart disease in fetuses with a prenatal diagnosis of a single isolated umbilical artery. METHODS: We performed a search strategy in MEDLINE (OVID), EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to the present. We assessed the risk of bias and performed a meta-analysis. We completed the subgroup analysis according to the region. RESULTS: We found 1384 studies by the search strategy. After carefully reviewing the full-text, 15 studies were included. A total of 2008 fetuses with a single isolated umbilical artery were included, and 177 had cardiac malformations. There was an overall incidence of 9% 95%CI (0.05-0.14) I2 90%. The incidence by country of origin was between 5% and 19%. The most common heart disease reported was a ventricular septal defect. Seven studies were found describing 25 cases. We described other malformations, such as tetralogy of Fallot, coarctation of the aorta, and hypoplastic left ventricle, among others. CONCLUSION: The incidence of congenital heart disease in fetuses with a single isolated umbilical artery was high. In addition, half of these correspond to significant heart disease. Based on the above, we suggest that fetuses with a single isolated umbilical artery should have a complete anatomic evaluation emphasizing cardiac evaluation.

The role of ultrasound and mitofusin-2 levels to predict pregnancy outcomes in patients with severe preeclampsia: a case-control study

SUMMARY OBJECTIVE: The aim of this study was to evaluate mitofusin-2 levels and fetal Doppler ultrasonography effects in patients with severe preeclampsia. METHODS: This single-center case-control study was conducted in the gynecology service of the university hospital in Van. A total of 90 pregnant women aged 18-40 years were included in the study. Of these, 30 are normal, 30 have mild preeclampsia, and 30 are pregnant with severe preeclampsia. In this study, especially in severe preeclampsia patients, serum mitofusin-2 levels and important fetal Doppler flows such as uterine arterial pressure, umbilical arterial pressure, and 1st and 5th minute Apgar scores, birth weight, and the relationship between postnatal outcomes such as week of birth and the number of patients in the neonatal intensive care unit were investigated. RESULTS: There was a significant difference between the three groups in terms of mitofusin-2 levels, which was the highest in the group (p<0.05). Maternal serum mitofusin-2 levels were positively correlated with uterine arterial pressure (r=0.543, p=0.007), umbilical arterial pressure (r=0.238, p=0.008), diastolic blood pressure, and systolic blood pressure (p<0.001). Receiver operating characteristic curve of mitofusin-2 in predicting preeclampsia is as follows: optimal cutoff 1.6 ng/mL; area under the curve: 0.861; 95%CI: 0.786-0.917; sensitivity: 83.9%; and specificity: 70.0%, (p≤0.001). A one-unit increase in mitofusin-2 resulted in a statistically significant 4.21-fold increase in preeclampsia risk. CONCLUSION: This study recommends the use of mitofusin-2 together with fetal Doppler ultrasound findings as a reliable indicator of preeclampsia severity.

Prevalencia de la arteria umbilical única en gestantes: su relación con otras malformaciones y el bajo peso al nacer

Introducción: La arteria umbilical única tiene una incidencia del 1 % en los recién nacidos. Se le asocia frecuentemente con gemelaridad, malformaciones y crecimiento intrauterino retardado, y constituye un factor de riesgo de prematuridad, muerte fetal y neonatal. Objetivos: Determinar la prevalencia de la arteria umbilical única en gestantes, y la asociación de esta entidad con otras malformaciones y el bajo peso al nacer. Materiales y métodos: Estudio descriptivo retrospectivo, con datos obtenidos de las historias clínicas y del modelo de seguimiento lineal existente en las consultas de genética comunitaria del municipio Matanzas, de enero de 2015 a diciembre de 2019. Resultados: La prevalencia de la arteria umbilical única fue del 0,3 %. Las malformaciones más frecuentes fueron las renales; el 27,7 % de los nacimientos fueron pretérmino y el 33,3 % de los nacidos fue con un peso inferior a 2500 g. Conclusiones: La arteria umbilical única constituye un marcador para otras malformaciones. Cuando coexisten ambas existe riesgo de prematuridad y bajo peso al nacer. Se recomienda realizar examen clínico posnatal a todo recién nacido con arteria umbilical única, pesquisando defectos renales y cardíacos.

Introduction: The single umbilical artery has an incidence of 1% in newborns. It is frequently associated with twinning, malformations and delayed intrauterine growth, and is a risk factor of prematurity, fetal and neonatal death. Objective: To determine the prevalence of single umbilical artery in pregnant women and the association of this entity with other malformations and low birth weight. Materials and methods: Retrospective descriptive study, with data obtained from medical records and the linear follow-up model existing in the community genetic clinics of the municipality of Matanzas, from January 2015 to December 2019. Results: The prevalence of the single umbilical artery was 0.3%. The most frequent malformations were renal ones; 27.7% of births were pre-term and 33.3% of those born weighed less than 2500g. Conclusions: The single umbilical artery is a marker for other malformations. When both coexist there is a risk of prematurity and low birth weight. Postnatal clinical examination is recommended for all newborns with single umbilical artery, checking for renal and heart defects.

Vasodilation promoted by (E,E)-farnesol involving ion channels in human umbilical arteries.

Background: (E,E)-farnesol is a sesquiterpene alcohol derived from plants and animals that exhibits pharmacological properties in the cardiovascular system. However, its effects on human umbilical vessels remain unknown. Purpose: Thus, this study aims to characterize the vasodilatory effect of (E,E)-farnesol in human umbilical arteries (HUA). Study design: The tissue is obtained from pregnant women over 18 years of age, normotensive, and without prepartum complications. After collected, the tissue was segmented and dissected to remove Wharton's jelly and obtain the umbilical arteries segments. Methods: HUA segments were isolated and sectioned into rings that were subjected to isometric tension recordings in an organ bath. Results: (E,E)-farnesol (1 µmol/L to 1 mmol/L) promoted vasodilatory effect in HUA preparations, affecting basal tone, and inhibiting the electromechanical coupling induced by KCl 60 mmol/L with greater potency (EC50 225.3 µmol/L) than the pharmacomechanical coupling induced by 5-HT 10 µmol/L (EC50 363.5 µmol/L). In the absence of extracellular calcium, pharmacomechanical coupling was also abolished, and contractions induced by CaCl2 or BaCl2 were attenuated by (E,E)-farnesol indicating a possible direct inhibition of L-type VOCC as a mechanism of the vasodilatory effect. The vasodilator efficacy of (E,E)-farnesol on reduction of vasocontraction induced by the presence of tetraethylammonium (1 or 10 mmol/L), 4-aminopyridine (1 mmol/L) and glibenclamide (10 µmol/L) suggesting a possible influence of different potassium channels (BKCa, KV and KATP). Conclusion: These results suggest that (E,E)-farnesol may be a promising pharmacological candidate for obstetric hypertensive disorders.

Craniofacial Microsomia, Associated Congenital Anomalies, and Risk Factors in 63 Cases from the Alberta Congenital Anomalies Surveillance System.

OBJECTIVE: To report associated congenital anomalies with unexplained craniofacial microsomia (CFM) and the phenotypic overlap with other recurrent constellations of embryonic malformations (RCEM), and to assess prenatal and perinatal risk factors. STUDY DESIGN: This is a retrospective cross-sectional study. Cases with CFM, delivered between January 1, 1997, and December 31, 2019, were abstracted from the population-based Alberta Congenital Anomalies Surveillance System. Livebirths, stillbirths, and early fetal losses were reviewed to include all types of pregnancy outcomes along the spectrum of this condition. Prenatal and perinatal risk factors were compared with the Alberta birth population to assess differences between the 2 groups. RESULTS: There were 63 cases with CFM, yielding a frequency of 1 per 16 949. There was a high rate of cases (65%) with anomalies outside the craniofacial and vertebral regions. Congenital heart defects were the most common (33.3%). A single umbilical artery was found in 12.7% of cases. The twin/triplet rate of 12.7% was significantly higher than the Alberta rate of 3.3% (P < .0001). There was an overlap with a second RCEM condition in 9.5% of cases. CONCLUSIONS: Although CFM is primarily a craniofacial condition, the majority of cases have congenital anomalies affecting other systems requiring additional assessments, including an echocardiogram, renal ultrasound examination, and a complete vertebral radiograph. The high rate of an associated single umbilical artery raises the possibility of a related etiological mechanism. Our findings support the proposed concept of RCEM conditions.

Effect of Lippia alba (Mill.) N.E. Brown Essential Oil on the Human Umbilical Artery.

Lippia alba is popularly known as lemon balm, with its essential oil (EO) cited for displaying antimicrobial, sedative, and vasorelaxant effects. Yet, its action on isolated human vessels has not been described in the literature. Thus, we evaluated the vasorelaxant effect of essential oil of L. alba (EOLa) on human umbilical arteries (HUA) isolated in organ baths. HUA rings were isolated, subjected to contractions induced by potassium chloride (KCl), serotonin (5-HT), or histamine (HIST) to record the isometric tension, and then treated with EOLa (30-1000 µg/mL). The EOLa showed a more prominent inhibitory effect on the pharmacomechanical coupling contraction via HIST with an EC50 value of 277.1 ± 8.5 µg/mL and maximum relaxant effect at 600 µg/mL. The addition of tetraethylammonium (TEA) or 4-aminopyridine (4-AP) in HUA preparations did not inhibit EOLa total relaxant effect at 1000 µg/mL. In the presence of gliblenclamide (GLI), the oil relaxed the HUA rings by 90.8% at maximum concentration. The EOLa was also investigated for its effects on voltage-operated calcium channels (VOCCs), where the HUA preincubation with this oil at 1000 µg/mL inhibited BaCl2 (0.1-30 mM)-induced contractions. This study demonstrates for the first time that EOla has a vasorelaxant effect on HUA and its particular blockade of VOCCs.

Pharmacological screening of species from the Lippia genus, content in terpenes and phenylpropanoids, and their vasorelaxing effects on human umbilical artery.

BACKGROUND: Naturally occurring bioactive compounds have a plethora of biological effects. OBJECTIVE: In this study, we examined a pharmacological screening of natural products on the human umbilical artery (HUA). METHODS: HUA preparations were used to follow contractions by KCl (60 mM) and tested at different concentrations (1-5000 µg/mL and µM) of the Lippia alba (EOLa) and Lippia origanoides (EOLo) essential oils, terpenes (citral, limonene perilic alcohol) and phenylpropanoids (eugenol, methyl eugenol). Discussion/Results: The reduction corresponded to approximately 100%, except for limonene (80±1.2 %). When evaluating the concentration of the natural product that promotes 50 % relaxation of the HUA contracted by KCL, EC50 values were: 424.3 µg/mL (EOLa); 468.7±6.7 µg/mL (EOLo); 264.2 ± 8.2 µM (citral); 677.8±5.4 µM (limonene); 186.3±6.4 µM (peryl alcohol); 986.4±7.9 µM (eugenol); and 279.1±4.4 µM (methyl-eugenol). Perillyl alcohol had a lower EC50 (consequently it has a higher pharmacological potency). CONCLUSION: The plant extracts have a promising vasorelaxing effect in HUAs, paving the way for future investigations: as applications in diseases related to these vessels, such as preeclampsia.

Prognostic factors and perinatal outcomes in early-onset intrauterine growth restriction due to placental insufficiency.

OBJECTIVE: To determine the principal prognostic factors and neonatal outcomes associated with perinatal death in cases of early-onset intrauterine growth restriction (IUGR) due to placental insufficiency and to define the cutoff point for the risk of perinatal death. METHODS: A retrospective cohort study conducted with 198 pregnant women with a diagnosis of early-onset IUGR (as detected before the 32nd week of gestational age). The association between the dependent variable (perinatal death) and the independent variables was investigated using a multivariate logistic regression model. The area under the receiver operating characteristic (ROC) curve was calculated to determine the sensitivity and specificity of the adjusted model. A significance level of 5% was established for the entire statistical analysis. RESULTS: Perinatal deaths occurred in 89 (44.9%) of the 198 fetuses with early-onset IUGR. Birthweight <800 grams (OR: 14.73; 95%CI: 4.13-52.54; p < .001), postnatal need for mechanical ventilation (OR: 24.56; 95%CI: 5.58-108.08; p < .001) and postnatal use of an oxygen hood (OR: 0.09; 95%CI: 0.02-0.39; p = .001) remained significantly associated with neonatal death in the multivariate model. The sensitivity, specificity, positive and negative predictive values for birthweight <800 grams and need for mechanical ventilation as predictors of death were, respectively, 84%, 91%, 88%, 88% and 93%, 71%, 60% and 96%, while the values for use of an oxygen hood were, respectively, 15%, 62%, 15% and 62%. CONCLUSION: The principal determinants of perinatal death in fetuses with early-onset IUGR were birthweight <800 grams, gestational age at delivery <30 weeks and postnatal need for mechanical ventilation as risk factors while postnatal use of an oxygen hood was found to constitute a protective factor.

Utilidad de la ecografía Doppler en el diagnóstico, el pronóstico y el manejo de la restricción del crecimiento fetal: situación en Chile / Usefulness of Doppler ultrasound for the diagnosis, prognosis and management of fetal growth restriction: situation in Chile

INTRODUCCIÓN: La restricción del crecimiento fetal (RCF) se define como la disminución patológica de la tasa de crecimiento fetal, generalmente asociada a insuficiencia placentaria. Se diagnostica mediante ultrasonografía obstétrica y velocimetría Doppler, pero no existe un consenso global respecto a los parámetros referenciados. OBJETIVO: Brindar una revisión actualizada de la aproximación clínica de la RCF en Chile, enfocada en el uso de la ultrasonografía Doppler como herramienta fundamental para el diagnóstico, el pronóstico y el manejo de esta patología, y realizar una comparativa con respecto a otros países. MÉTODO: Se realizó una revisión con palabras clave en las bases de datos PubMed y SciELO. RESULTADOS: Se obtuvieron 89 referencias bibliográficas, logrando una revisión de datos actualizados del uso del Doppler en la RCF tanto en el mundo como en Chile. CONCLUSIONES: La Guía Perinatal 2015 publicada en Chile carece de actualización con los conocimientos y la evidencia científica más recientes. Sin embargo, concuerda en gran parte con los lineamientos y las pautas generales de manejo de la RCF de las diferentes guías clínicas analizadas. Las discrepancias entre las guías revisadas podrían explicarse por la gran variabilidad de la evidencia de los estudios científico-clínicos, los cuales es importante unificar a través de una guía que promueva una estandarización de la atención de la RCF en el país.

INTRODUCTION: Fetal growth restriction (FGR) is the pathological decrease in the fetal growth rate generally associated with placental insufficiency. Diagnosis is made by obstetric ultrasonography and Doppler velocimetry, assessing different biometric and hemodynamic parameters. However, there is no global consensus regarding the parameters to be referenced. OBJECTIVE: To provide an updated review of the FGR clinical approach in Chile, focused on the use of Doppler ultrasonography as a fundamental tool in the diagnosis, prognosis, and management of this pathology and to compare with other countries. METHOD: A literature search was conducted in the PubMed and SciELO databases, including relevant and updated articles. RESULTS: The search included 89 bibliographic references under which it was possible to make a review of the most current data on the use of Doppler in FGR both worldwide and in Chile. CONCLUSIONS: The 2015 Perinatal Guidelines published in Chile is not updated with the latest scientific evidence and knowledge. However, it largely agrees with international guidelines for FGR management. The discrepancies between the revised guidelines could be explained due to the variability of evidence from scientific-clinical studies, which are essential to unify for standardized care of FGR in the country.

Doppler Ultrasound of the Umbilical Artery: Clinical Application / Ultrassonografia Doppler da artéria umbilical: Aplicação clínica

Abstract Objective To provide a survey of relevant literature on umbilical artery Doppler ultrasound use in clinical practice, technical considerations and limitations, and future perspectives. Methods Literature searches were conducted in PubMed and Medline, restricted to articles written in English. Additionally, the references of all analyzed studies were searched to obtain necessary information. Results The use of this technique as a routine surveillance method is only recommended for high-risk pregnancies with impaired placentation. Meta-analyses of randomized trials have established that obstetric management guided by umbilical artery Doppler findings can improve perinatal mortality and morbidity. The values of the indices of Umbilical artery Doppler decrease with advancing gestational age; however, a lack of consensus on reference ranges prevails. Conclusion Important clinical decisions are based on the information obtained with umbilical artery Doppler ultrasound. Future efforts in research are imperative to overcome the current limitations of the technique.

Resumo Objetivo Compilar informação relevante proveniente da literatura atual sobre a ultrassonografia Doppler das artérias umbilicais (AUs) na prática clínica, considerações e limitações técnicas e perspectivas futuras. Métodos A pesquisa bibliográfica foi realizada nos bancos de dados PubMed e Medline e restringiu-se a artigos escritos na língua inglesa. Recorreu-se também à bibliografia dos artigos selecionados, quando necessário, para obter informação relevante. Resultados A utilização desta técnica como método de vigilância de rotina está apenas recomendada emgravidezes de alto risco comdisfunção placentar.Metanálises de estudos randomizados mostraram que o seguimento obstétrico baseado nos achados do Doppler da artéria umbilical pode melhorar a mortalidade e a morbilidade perinatal. É consensual que os valores dos índices Doppler da AU decrescem com o avanço da idade gestacional. No entanto, há ainda muita incerteza quanto aos valores de referência. Conclusão As informações obtidas através da AU Doppler US são a base para muitas decisões clínicas importantes. Trabalhos de investigação nesta área são essenciais para tentar colmatar atuais limitações da técnica.

Presumed normal hemodynamic values of the arteries in the final third period of gestation in bitches

Background: Doppler ultrasonography enables the investigation of vascular blood flow indexes in gestational assessment,being able to detect vascular resistances that can affect fetal and maternal circulation, such as cases of placental insufficiency, associated with fetal cerebral oxygenation deficit and fetal distress. The study aims to assume hemodynamicallynormal values in the final third of gestation in bitches, of the umbilical, uteroplacental, middle cerebral and internal carotidarteries, correlating the obtained Doppler velocimetric indexes, for the assessment of the feto-placental circulation, andprediction of fetal viability indexes, fetal centralization and probable date of delivery.Materials, Methods & Results: Thirty healthy bitches were examined in the final third of gestation (40-60 days). Thesewere evaluated by Doppler ultrasonography at 2 times (T): T1: between 40-50 days; T2: between 51-60 of gestation.At each time point, the peak systolic velocities (PSV) and end-diastolic velocities (EDV) used to obtain the pulsatility(IP) and resistivity (IR) indexes of the umbilical, uteroplacental, middle cerebral and internal carotid arteries of fetuseswere evaluated. Also, the systole/diastole (S/D) ratio of these vessels was evaluated. The data obtained were subjected toanalysis of variance and Tukey test, using a P value equal to 5%. A significant difference was observed between velocitiesand Doppler velocimetric indexes between the 2 phases of the gestational final third in all studied vessels. There was anincrease in the values of PSV and EDV and a decrease in the indexes, as the probable date of delivery approached. Theanalysis of the umbilical cord IR showed an increase from P1 to P2 (P < 0.05), while the IP decreased at the same time.For all studied variables there was a statistically significant difference (P < 0.05). In the uteroplacental...(AU)

Umbilical artery pulsatility index and half-peak systolic velocity in second- and third-trimester fetuses with trisomy 18 and 13.

OBJECTIVES: To analyze umbilical artery (UA) Doppler velocimetry and its possible role in placenta-mediated fetal growth restriction (FGR) in second- and third-trimester fetuses with trisomy 18 and 13. METHODS: UA pulsatility index (PI) and half-peak systolic velocity deceleration time (hPSV-DT) were measured in fetuses with trisomy 18 and 13. Correlation with gestational age, birthweight, and perinatal outcome was analyzed. RESULTS: A total of 80 measurements were taken from 33 fetuses with trisomy 18 and 19 with trisomy 13. Overall, there was a high prevalence of abnormal UA Doppler velocimetry. In fetuses with trisomy 18, 54% (27/50) of the UA PI values and 58% (29/50) of the UA hPSV-DT values were abnormal. In fetuses with trisomy 13, 80% (24/30) of the UA PI values and 87% (26/30) of the UA hPSV-DT values were abnormal. The prevalence of abnormal UA Doppler velocimetry increased with gestational age in both types of aneuploidy. However, this trend was only significant for trisomy 13 (p<0.05). All fetuses with trisomy 18 and 86% of fetuses with trisomy 13 were classified at birth as FGR. There were no perinatal survivors in this series. CONCLUSIONS: A high prevalence of abnormal UA Doppler velocimetry was found in second- and third-trimester fetuses with trisomy 18 and 13, which further increased with gestational age. These results may well correlate with alterations described previously in the placenta, suggesting placental insufficiency has an important role in the development of FGR in these autosomal aneuploid fetuses.

Presumed normal hemodynamic values of the arteries in the final third period of gestation in bitches

Background: Doppler ultrasonography enables the investigation of vascular blood flow indexes in gestational assessment,being able to detect vascular resistances that can affect fetal and maternal circulation, such as cases of placental insufficiency, associated with fetal cerebral oxygenation deficit and fetal distress. The study aims to assume hemodynamicallynormal values in the final third of gestation in bitches, of the umbilical, uteroplacental, middle cerebral and internal carotidarteries, correlating the obtained Doppler velocimetric indexes, for the assessment of the feto-placental circulation, andprediction of fetal viability indexes, fetal centralization and probable date of delivery.Materials, Methods & Results: Thirty healthy bitches were examined in the final third of gestation (40-60 days). Thesewere evaluated by Doppler ultrasonography at 2 times (T): T1: between 40-50 days; T2: between 51-60 of gestation.At each time point, the peak systolic velocities (PSV) and end-diastolic velocities (EDV) used to obtain the pulsatility(IP) and resistivity (IR) indexes of the umbilical, uteroplacental, middle cerebral and internal carotid arteries of fetuseswere evaluated. Also, the systole/diastole (S/D) ratio of these vessels was evaluated. The data obtained were subjected toanalysis of variance and Tukey test, using a P value equal to 5%. A significant difference was observed between velocitiesand Doppler velocimetric indexes between the 2 phases of the gestational final third in all studied vessels. There was anincrease in the values of PSV and EDV and a decrease in the indexes, as the probable date of delivery approached. Theanalysis of the umbilical cord IR showed an increase from P1 to P2 (P < 0.05), while the IP decreased at the same time.For all studied variables there was a statistically significant difference (P < 0.05). In the uteroplacental...

Lateral Compartment Endometriosis is Associated with Retraction of the Obliterated Umbilical Artery.

BACKGROUND AND OBJECTIVES: Based on laparoscopic views, we hypothesized that the involvement of the lateral compartment of the pelvis (LCP) by deep infiltrating endometriosis can be inferred by observing retraction of the obliterated umbilical artery (OUA) toward the abdominal cavity. We sought to verify the association between the retraction of the OUA and the presence of endometriosis in the ipsilateral LCP (parametrium, paracervix, or paracolpium). METHODS: This preplanned, retrospective, cross-sectional study evaluated 76 women with deep endometriosis at a private referral center. Using magnetic resonance imaging, the retraction of OUA was represented by its distance from the rectus abdominis (four different measurements were used). The diameter of the OUA was also measured and considered. T2-weighted imaging of the pelvis were obtained in two planes (sagittal and axial) and from two reference points: the proximal angle of the artery (measurement 1) and a point immediately above (measurement 2). The measurements were assessed through an exploratory multivariate principal component analysis. The associations were tested using the bivariate, non-parametric statistical Mann-Whitney U test. RESULTS: The presence of endometriosis of all LCP examined was 34.2% (95% confidence interval: 26.8-41.7) with the highest percentage in the paracervix. The retraction of the OUA was greater in women with endometriosis in the ipsilateral LCP for all four measurements and was statistically significant for three of them: Sagittal 1 (p = .011), Sagittal 2 (p = .015), Axial 1 (p = .021), and Axial 2 (p = .093). The OUA diameter was not associated with its retraction (p = .392). CONCLUSION: Retraction of the OUA toward the abdominal cavity is associated with the presence of endometriosis in the ipsilateral paracervix.

Perinatal Outcome of Selective Intrauterine Growth Restriction in Monochorionic Twins: Evaluation of a Retrospective Cohort in a Developing Country.

Selective intrauterine growth restriction (sIUGR) in monochorionic twin pregnancies is associated with greater morbidity and mortality for both fetuses when compared to singleton and dichorionic pregnancies. This retrospective cohort study aimed to assess the perinatal outcomes of monochorionic twin pregnancies affected by this disorder and conducted expectantly, by analyzing the results according to the end-diastolic flow in the umbilical artery Doppler of the smaller twin (type I: persistently forward/type II: persistently absent or reversed/type III: intermittently absent or reversed). Seventy-five monochorionic diamniotic twin pregnancies with sIUGR were included in this study. sIUGR was defined by estimated fetal weight below the 3rd centile for gestational age, or below the 10th centile, when associated with at least one of the following three criteria: abdominal circumference below the 10th percentile, umbilical artery pulsatility index of the smaller twin above the 95th percentile, or estimated fetal weight discordance of 25% or more. Perinatal outcomes were analyzed from the prenatal period to hospital discharge and included perinatal death, neurological injury, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and sepsis. The mortality rate was 1.33% in this cohort. The overall morbidity rate was lower in type I twin pregnancies. In conclusion, this study shows that sIUGR type I has lower morbidity than types II and III in expectant management.

Endothelium-derived dopamine modulates EFS-induced contractions of human umbilical vessels.

Electrical field stimulation (EFS) induces contractions of both snake aorta and human umbilical cord vessels (HUCV) which were dependent on the presence of the endothelium. This study aimed to establish the nature of the mediator(s) responsible for EFS-induced contractions in HUCV. Rings with or without endothelium from human umbilical artery (HUA) or vein (HUV) were mounted in organ bath chambers containing oxygenated, heated Krebs-Henseleit's solution. Basal release of dopamine (DA), noradrenaline, and adrenaline was measured by LC-MS-MS. Cumulative concentration-response curves were performed with dopamine in the absence and in the presence of L-NAME or of dopamine antagonists. EFS studies were performed in the presence and absence of L-NAME, the α-adrenergic blockers prazosin and idazoxan, and the dopamine antagonists SCH-23390 and haloperidol. Tyrosine hydroxylase (TH) and dopa-decarboxylase (DDC) were studied by immunohistochemistry and fluorescence in situ hybridizations. Basal release of dopamine requires an intact endothelium in both HUA and HUV. TH and DDC are present only in the endothelium of both HUA and HUV as determined by immunohistochemistry. Dopamine induced contractions in HUA only in the presence of L-NAME. Dopamine-induced contractions in HUV were strongly potentiated by L-NAME. The EFS-induced contractions in both HUA and HUV were potentiated by L-NAME and inhibited by the D2-like receptor antagonist haloperidol. The α-adrenergic antagonists prazosin and idazoxan and the D1-like receptor antagonist SCH-23390 had no effect on the EFS-induced contractions of HUA and HUV. Endothelium-derived dopamine is a major modulator of HUCV reactivity in vitro.