Spiral Arteries in Second Trimester of Pregnancy: When Is It Possible to Define Expected Physiological Remodeling as Abnormal?

After undergoing remodeling, uterine spiral arteries turn into wide, flexible tubes, with low resistance. If remodeling does not occur, spontaneous abortions, intrauterine growth restriction, and pregnancy-related hypertensive disorders can ensue. Arterial transformation begins at a very early gestational stage; however, second quarter pregnancy histopathological samples have yet to pinpoint the exact moment when abnormal remodeling transpires. We examined 100 samples, taken from consecutive abortions at 12-23 gestational weeks. Following Pijnenborg and Smith guidelines, blinded pathologists analyzed clinical data on remodeling stages. Lab results showed that arterial remodeling is not synchronic in all vessels; a single sample can include various remodeling stages; neither is remodeling homogenous in a single vessel: change may be occurring in one part of the vessel, but not in another. To our knowledge, no one has published this finding. In the examined age group, Smith stage IV predominates; around week 14, substantial muscle and endothelium loss takes place. After week 17, endovascular or fibrin trophoblast does not usually occur. Although scant consensus exists on what defines preeclampsia etiology, it is clear that it involves abnormal remodeling in decidua vessels. Improved understanding requires further knowledge on both the physiological and pathological aspects of the remodeling process. We observed that muscle and endothelial tissues disappear from weeks 14-17, after which time reendothelization predominates. We list the expected proportion of spiral artery changes for each gestational age which, to date, has not been available.

Can increased resistance to uterine artery flow be a risk factor for adverse neurodevelopmental outcomes in childhood? A prospective cohort study.

A prospective cohort study was conducted to determine whether an increased uterine artery pulsatility index (UtA-PI) in the second trimester of pregnancy is a risk factor for neurodevelopmental outcomes in children 2-3 years of age. A group of pregnant women with a UtA-PI below the 90th percentile (P90) and a second group with a UtA-PI ≥ P90 in the second trimester were included in this study. The children of these women were evaluated during their second or third year of life using the Bayley III Screening Test. A total of 858 pregnancies with UtA-PI < P90 and 96 pregnancies with UtA-PI ≥ 90 were studied. The differences between the groups related to UtA-PI ≥ 90 were detected in relation to the variables of the Caucasian ethnicity, hypertension, newborn weight and stay in the intensive care unit after birth. However, adjusted neurodevelopmental outcomes did not differ between the groups: OR 0.53 (95% CI 0.27-1.04%). This study failed to demonstrate that the UtA-PI is a risk factor for adverse neurodevelopment in children.Impact statementWhat is already known on this subject? Early interventions in children at high risk for neurodevelopmental deficiency have proved to be beneficial. The complications associated with gestation and delivery negatively influence neurodevelopment. Several studies have shown that some adverse pregnancy outcomes such as preeclampsia, foetal growth restriction and foetal death can be predicted by increased resistance to flow in the uterine artery in the second trimester. However, there are no studies evaluating the association of the uterine artery with neurodevelopmental results.What do the results of this study add? This study concludes that neurodevelopment is influenced by multiple environmental and intrinsic factors and cannot be predicted by only one variable, such as the uterine artery blood flow. The brain has repair mechanisms to attenuate insults that occur during gestation and delivery.What are the implications of these findings for clinical practice and/or further research? This study was unable to demonstrate that blood flow in the uterine artery is a risk factor for neurodevelopment. Different, larger studies should be conducted by combining other factors with the uterine artery in an algorithm to allow the early identification of children at risk for neurodevelopmental impairment.

Preeclampsia in 2018: Revisiting Concepts, Physiopathology, and Prediction.

Preeclampsia currently remains one of the leading causes of death and severe maternal morbidity. Although its prevalence is still underestimated in some places due to underreporting, preeclampsia is a disease that health professionals need to know how to deal with and take action. For this reason, the studies about the theme remain along with the advances in their understanding that often implies improvement and change of concepts and conducts. The complexity of its etiology is a challenge and requires further studies for its full understanding. Apparently, poor adaptation of the maternal organism to the conceptus, marked by the nonoccurrence of changes in the uterine spiral arteries, determines a series of systemic repercussions that compound the various forms of preeclampsia presentation. In recent years, the use of acetylsalicylic acid to prevent cases of early onset of the disease has been consolidated and, alongside, studies have advanced the development of accessible and effective methods of identifying women at risk of preeclampsia. The aim of this review is to discuss updates on the occurrence, concept, pathophysiology, repercussion, prevention, and prediction of preeclampsia.

Perinatal outcome and placental apoptosis in patients with late-onset pre-eclampsia and abnormal uterine artery Doppler at diagnosis.

OBJECTIVE: To determine the rate of placental apoptosis and adverse perinatal outcome in patients with late-onset pre-eclampsia (PE) and abnormal uterine artery (UtA) Doppler at diagnosis. METHODS: This was a prospective cohort study of women with singleton pregnancy diagnosed with late PE, performed between August 2011 and January 2014 at the Maternal-Fetal Medicine Unit of Hospital Carlos Van Buren. Patients were stratified according to UtA Doppler status at diagnosis (pulsatility index (PI) ≤ or > 95th percentile). Logistic regression analysis was performed to identify associations between abnormal UtA Doppler and adverse maternal and perinatal outcomes. In a subset of this cohort for whom placental samples were available, immunohistochemical analysis of the placenta was performed to identify the rate of apoptosis and its association with UtA Doppler by comparing samples from those with normal and those with abnormal UtA Doppler and normotensive controls. Non-parametric linear trend analysis was performed for assessment of the apoptotic index. RESULTS: Eighty-six patients were included in the final analysis. Of these, UtA-PI was above the 95th percentile in 33 (38.4%) patients. Gestational age at diagnosis and delivery were significantly lower in this group compared with patients with normal UtA Doppler. Abnormal UtA Doppler was associated with increased risk of severe PE (odds ratio (OR) = 7.5; 95% CI, 2.76-20.46; P < 0.001), late preterm delivery (OR = 13.7; 95% CI, 4.53-41.46; P < 0.001), small-for-gestational age at birth (OR = 12.3; 95% CI, 3.17-47.57; P < 0.001) and admission to the neonatal intensive care unit (OR = 12.8; 95% CI, 2.61-62.36; P = 0.002). Moreover, UtA Z-score demonstrated a significant inverse correlation with birth-weight Z-score (r = -0.34; P = 0.0013). Mean placental apoptotic index demonstrated an ascending linear trend according to UtA Doppler status (P = 0.04). CONCLUSIONS: In patients with late PE, UtA Doppler was useful for clinical classification and as an indicator of placental histological findings. Correlation between UtA Doppler and the apoptotic index provides new evidence of a subgroup of late PE with a placental origin. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Uterine artery Doppler flow velocimetry parameters for predicting gestational trophoblastic neoplasia after complete hydatidiform mole, a prospective cohort study.

OBJECTIVES:: Doppler ultrasonography can be used to assess neoangiogenesis, a characteristic feature of postmolar gestational trophoblastic neoplasia. However, there is limited information on whether uterine artery Doppler flow velocimetry parameters can predict gestational trophoblastic neoplasia following a complete hydatidiform mole. The purpose of this study was as follows: 1) to compare uterine blood flow before and after complete mole evacuation between women who developed postmolar gestational trophoblastic neoplasia and those who achieved spontaneous remission, 2) to assess the usefulness of uterine Doppler parameters as predictors of postmolar gestational trophoblastic neoplasia and to determine the best parameters and cutoff values for predicting postmolar gestational trophoblastic neoplasia. METHODS:: This prospective cohort study included 246 patients with a complete mole who were treated at three different trophoblastic diseases centers between 2013 and 2014. The pulsatility index, resistivity index, and systolic/diastolic ratio were measured by Doppler flow velocimetry before and 4-6 weeks after molar evacuation. Statistical analysis was performed using Wilcoxon's test, logistic regression, and ROC analysis. RESULTS:: No differences in pre- and post-evacuation Doppler measurements were observed in patients who developed postmolar gestational trophoblastic neoplasia. In those with spontaneous remission, the pulsatility index and systolic/diastolic ratio were increased after evacuation. The pre- and post-evacuation pulsatility indices were significantly lower in patients with gestational trophoblastic neoplasia (odds ratio of 13.9-30.5). A pre-evacuation pulsatility index ≤1.38 (77% sensitivity and 82% specificity) and post-evacuation pulsatility index ≤1.77 (79% sensitivity and 86% specificity) were significantly predictive of gestational trophoblastic neoplasia. CONCLUSIONS:: Uterine Doppler flow velocimetry measurements, particularly pre- and post-molar evacuation pulsatility indices, can be useful for predicting postmolar gestational trophoblastic neoplasia.

Doppler velocimetry in fetal rats exposed to enoxaparin and unfractionated heparin (UFH) during pregnancy.

PURPOSE:: To evaluate the effects of enoxaparin and unfractionated heparin (UFH) administered in prophylactic and therapeutic doses on fetal vessels in healthy pregnant Wistar rats, according to Doppler velocimetry measurements. METHODS:: Fifty animals were assigned to one of five groups: controls (saline), prophylactic and therapeutic enoxaparin (1 and 2 mg/kg/day, respectively), and prophylactic and therapeutic UFH (72 and 400 UI/kg/day, respectively). Uterine horns were examined by ultrasound for identification of live fetuses. A sample of these fetuses underwent Doppler velocimetry. Spectral curves, peak systolic velocity (PSV), pulsatility index (PI), and resistance index (RI) of the middle cerebral artery, ductus venosus, and umbilical artery were investigated. Differences were considered statistically significant when p<0.05. RESULTS:: No significant differences in PSV, PI, or RI values were observed among the groups. CONCLUSION:: Doppler velocimetry measurements revealed no significant effects of enoxaparin or unfractionated heparin on fetal vessels in pregnant Wistar rats.

Uterine artery Doppler flow velocimetry parameters for predicting gestational trophoblastic neoplasia after complete hydatidiform mole, a prospective cohort study

OBJECTIVES: Doppler ultrasonography can be used to assess neoangiogenesis, a characteristic feature of postmolar gestational trophoblastic neoplasia. However, there is limited information on whether uterine artery Doppler flow velocimetry parameters can predict gestational trophoblastic neoplasia following a complete hydatidiform mole. The purpose of this study was as follows: 1) to compare uterine blood flow before and after complete mole evacuation between women who developed postmolar gestational trophoblastic neoplasia and those who achieved spontaneous remission, 2) to assess the usefulness of uterine Doppler parameters as predictors of postmolar gestational trophoblastic neoplasia and to determine the best parameters and cutoff values for predicting postmolar gestational trophoblastic neoplasia. METHODS: This prospective cohort study included 246 patients with a complete mole who were treated at three different trophoblastic diseases centers between 2013 and 2014. The pulsatility index, resistivity index, and systolic/diastolic ratio were measured by Doppler flow velocimetry before and 4-6 weeks after molar evacuation. Statistical analysis was performed using Wilcoxon’s test, logistic regression, and ROC analysis. RESULTS: No differences in pre- and post-evacuation Doppler measurements were observed in patients who developed postmolar gestational trophoblastic neoplasia. In those with spontaneous remission, the pulsatility index and systolic/diastolic ratio were increased after evacuation. The pre- and post-evacuation pulsatility indices were significantly lower in patients with gestational trophoblastic neoplasia (odds ratio of 13.9-30.5). A pre-evacuation pulsatility index ≤1.38 (77% sensitivity and 82% specificity) and post-evacuation pulsatility index ≤1.77 (79% sensitivity and 86% specificity) were significantly predictive of gestational trophoblastic neoplasia. CONCLUSIONS: Uterine Doppler flow velocimetry measurements, particularly pre- and post-molar evacuation pulsatility indices, can be useful for predicting postmolar gestational trophoblastic neoplasia.

Doppler velocimetry in fetal rats exposed to enoxaparin and unfractionated heparin (UFH) during pregnancy

Abstract Purpose: To evaluate the effects of enoxaparin and unfractionated heparin (UFH) administered in prophylactic and therapeutic doses on fetal vessels in healthy pregnant Wistar rats, according to Doppler velocimetry measurements. Methods: Fifty animals were assigned to one of five groups: controls (saline), prophylactic and therapeutic enoxaparin (1 and 2 mg/kg/day, respectively), and prophylactic and therapeutic UFH (72 and 400 UI/kg/day, respectively). Uterine horns were examined by ultrasound for identification of live fetuses. A sample of these fetuses underwent Doppler velocimetry. Spectral curves, peak systolic velocity (PSV), pulsatility index (PI), and resistance index (RI) of the middle cerebral artery, ductus venosus, and umbilical artery were investigated. Differences were considered statistically significant when p<0.05. Results: No significant differences in PSV, PI, or RI values were observed among the groups. Conclusion: Doppler velocimetry measurements revealed no significant effects of enoxaparin or unfractionated heparin on fetal vessels in pregnant Wistar rats.

Defective trophoblast invasion underlies fetal growth restriction and preeclampsia-like symptoms in the stroke-prone spontaneously hypertensive rat.

STUDY QUESTION: What is the impact of chronic hypertension on placental development, fetal growth and maternal outcome in the stroke-prone spontaneously hypertensive rat (SHRSP)? SUMMARY ANSWER: SHRSP showed an impaired remodeling of the spiral arteries and abnormal pattern of trophoblast invasion during placentation, which were associated with subsequent maternal glomerular injury and increased baseline hypertension as well as placental insufficiency and asymmetric fetal growth restriction (FGR). WHAT IS KNOWN ALREADY: A hallmark in the pathogenesis of preeclampsia (PE) is abnormal placentation with defective remodeling of the spiral arteries preceding the onset of the maternal syndrome. Pregnancies affected by chronic hypertension display an increased risk for PE, often associated with poor maternal and fetal outcomes. However, the impact of chronic hypertension on the placentation process as well as the nature of the factors promoting the development of PE in pregnant hypertensive women remain elusive. STUDY DESIGN, SIZE, DURATION: Timed pregnancies [n = 5] were established by mating 10-12-week-old SHRSP and Wistar Kyoto (WKY, normotensive controls) females with congenic males. Maternal systolic blood pressures (SBPs) were recorded pre-mating, throughout pregnancy (GD1-19) and post-partum by the tail-cuff method. On selected dates, 24 h urine- and blood samples were collected, and animals were euthanized for isolation of implantation sites and kidneys for morphometrical analyses. PARTICIPANTS/MATERIALS, SETTING, METHODS: The 24 h proteinuria and the albumin:creatinine ratio were used for evaluation of maternal renal function. Renal injury was assessed on periodic acid Schiff, Masson's trichrome and Sirius red stainings. Placental and fetal weights were recorded on gestation day (GD)18 and GD20, followed by determination of fetal cephalization indexes and developmental stage, according to the Witschi scale. Morphometric analyses of placental development were conducted on hematoxylin-eosin stained tissue sections collected on GD14 and GD18, and complemented with immunohistochemical evaluation of isolectin B4 binding for assessment of placental vascularization. Analyses of vascular wall alpha actin content, perforin-positive natural killer (NK) cells and cytokeratin expression by immunohistochemistry were used for evaluation of spiral artery remodeling and trophoblast invasion. MAIN RESULTS AND THE ROLE OF CHANCE: SHRSP females presented significantly increased SBP records from GD13 to GD17 (SBPGD13 = 183.9 ± 3.9 mmHg, P < 0.005 versus baseline) and increased proteinuria at GD18 (P < 0.01 versus WKY). Histological examination of GD18 kidneys revealed glomerular enlargement and mesangial matrix expansion, which were not evident in pregnant WKY or age-matched virgin SHRSP. At GD20, SHRSP displayed a significant reduction of placental mass (P < 0.01 versus WKY) and signs of placental insufficiency (i.e. hypertrophy and reduced branching morphogenesis of the labyrinth layer), associated with decreased offspring weights and increased cephalization index (both P < 0.001 versus WKY) indicating asymmetric FGR. Notably, SHRSP placentas displayed an incomplete remodeling of spiral arteries starting as early as GD14, with luminal narrowing and reduced densities of perivascular NK cells followed by decreased infiltration of endovascular trophoblasts at GD18. LARGE SCALE DATA: n/a. LIMITATIONS, REASONS FOR CAUTION: A pitfall of the present study is the differences in the blood pressure profiles between rats and humans (i.e. unlike pregnancies affected by PE, blood pressure in SHRSP and other hypertensive rat models decreases pre-delivery), which limits extrapolation of the results. WIDER IMPLICATIONS OF THE FINDINGS: Our findings provide new insights on the role of chronic hypertension as a risk factor for PE by interfering with early events during the placentation process. The SHRSP strain represents an attractive model for further studies aimed at addressing the relative contribution of intrinsic (i.e. placental) and extrinsic (i.e. decidual/vascular) factors to defective spiral artery remodeling in pregnancies affected by PE. STUDY FUNDING AND COMPETING INTEREST(S): This work was supported by research grants from Fundación Florencio Fiorini to G.B., from Charité Stiftung to S.M.B. and University of Buenos Aires (UBACyt) to J.T. The authors have no competing interests to declare.

Cystic endometrial hyperplasia-pyometra syndrome in bitches: identification of hemodynamic, inflammatory, and cell proliferation changes.

Cystic endometrial hyperplasia (CEH)-pyometra syndrome is one of the most common diseases of noncastrated female dogs. However, determination of etiological mechanisms and differential diagnosis of CEH-pyometra syndrome are undefined. The aim of this study is to compare immunohistochemically the expression of cyclooxygenase-2 (COX-2) inflammatory mediator, Ki-67 antigen proliferation marker, vascular endothelial growth factor (VEGF-A) angiogenesis mediator and its FLT-1 and KDR receptors, and correlate with Doppler velocimetry of uterine artery and endometrial vascularization in bitches with CEH-pyometra syndrome. Bitches were allocated into CEH-mucometra Group (n = 13), Pyometra Group (n = 11), and Control Group (n = 8). Pyometra Group presented cytoplasmatic staining intensity for COX-2, VEGF-A, and FLT-1 and KDR receptors in luminal epithelium cells significantly higher compared to CEH-mucometra and Control groups. For the glandular epithelium, Pyometra Group had higher immunostaining score for VEGF-A and its receptors (FLT-1 and KDR). Hemodynamic indexes showed negative correlation with VEGF-A and its receptors as well as with COX-2. On the other hand, uterine vascularization score showed positive correlation in relation to immunostaining of COX-2, VEGF-A, and receptors in the endometrium luminal epithelium. In conclusion, uterus of bitches with CEH-pyometra syndrome show inflammatory process characterized by COX-2 expression, resulting in greater expression of proliferative Ki-67 marker as tissue response against the infectious agent. Furthermore, the increased VEGF-A expression and its receptors in CEH-pyometra reflect the increased blood flow and lower vascular resistance. Therefore, canine pyometra is characterized by an inflammatory, proliferative, and vascular disorder.

Uterine and umbilical artery Doppler at 28 weeks for predicting adverse pregnancy outcomes in women with abnormal uterine artery Doppler findings in the early second trimester.

OBJECTIVE: The objective of this study was to determine the contribution of uterine (UtA) and umbilical arteries (UA) Doppler examination at 28 weeks to predict adverse pregnancy outcomes in women who had increased resistance in UtA in the early second trimester. METHODS: Women with UtA mean pulsatility index (PI) above the 95th centile at 19-22 weeks of gestation were offered a growth scan including Doppler examination of UtA and UA at 28 weeks. Adverse pregnancy outcomes included small for gestational age (SGA), defined as birth weight below the tenth centile, preeclampsia (PE) and early-onset PE (PE before 34 weeks). RESULTS: We studied 266 pregnant women with elevated PI in the UtAs in the second trimester and ultrasound reassessment at 28 weeks. UtA PI >95th centile at 28 weeks was associated with subsequent PE [odds ratio (OR): 10.0, 95% CI: 2.3-43.5], early-onset PE (OR: 57.7, 95% CI: 3.8-87.6) and SGA less than the tenth centile (OR: 5.5, 2.2-13.9). UA PI >95th centile at 28 weeks was not significantly associated with any adverse outcome. CONCLUSIONS: In women with abnormal UtA Doppler in the early second trimester scan, persistence of elevated UtA PI, but not abnormal UA PI, is associated with adverse pregnancy outcomes including PE, early-onset PE and SGA. © 2014 John Wiley & Sons, Ltd.

Maternal cerebral centralization of blood flow in pregnant women with specific gestational hypertension / Centralização cerebral do fluxo sanguíneo materno em grávidascom hipertensão gestacional específica

Objectives: To evaluate the occurrence of maternal brain centralization in pregnant women with specific gestational hypertension; to establish normal values of the ratio of the uterine artery with (mean and standard deviation) ophthalmic artery; to compare the ratio of uterine to the ophthalmic artery with normal and abnormal groups; and to establish the Receiver Operator Curve (ROC) for diagnosis of patients with specific hypertensive disease of pregnancy. Methods: To achieve the proposed objectives a case–control study was carried out where the sample consisted of 178 pregnant patients divided into two groups. The control group included pregnant 83 pregnant normotensive women; a case group included 95 patients with clinical and laboratory diagnoses of specific gestational hypertension. Results: Patients with preeclampsia had lower values than the patients who had eclampsia. The Doppler parameters that were statistically significant were those of the ratio of uterine artery with the ophthalmic artery (AU/AO) and vice versa. A comparison between the normal curve systole–diastole and the respective cut-off point was performed. A ROC is shown in the cut-off considering the systolic velocity, the diastolic velocity, the systole/diastole relation, and the index of resistance of the ophthalmic artery. Conclusion: The maternal centralization in high risk pregnancies was observed when specific gestational hypertension is real. The normal curve has a mean and standard deviation of the relative Doppler of the uterine artery to the ophthalmic artery systolic/diastolic ratio was 0.43 ± 0.16 for normal pregnant patients. Comparing the group of patients with normal pathological group of patients there was a statistically significant difference between them considering the relation of Doppler uterine artery with ophthalmic artery.(...)

Objetivos: Avaliar a ocorrência de centralização no cérebro materno em grávidas com hipertensão gestacional específica; estabelecer os valores normais (média e desvio padrão)da razão artéria uterina/artéria oftálmica; comparar a razão artéria uterina/artéria oftálmica entre grupos normal e enfermo; estabelecer a curva ROC para o diagnóstico de pacientes com doença hipertensiva específica da gravidez. Métodos: Estudo de caso-controle em uma amostra de 178 pacientes gestantes, divididas em dois grupos. O grupo controle consistiu em 83 grávidas normotensas; o grupo de casos consistiu em 95 pacientes com diagnóstico clínico e laboratorial de hipertensão gestacional específica. Resultados: Pacientes com pré-eclâmpsia apresentaram valores mais baixos versus pacientes que sofreram eclampsia. Os parâmetros da sonografia Doppler estatisticamente significativos foram os referentes à relação artéria uterina/artéria oftálmica (AU/AO) e vice versa. Foi traçada uma curva de normalidade para sístole-diástole de comparação com os respectivos pontos de corte. A curva ROC exibe os pontos de corte, respectivamente, para velocidade sistólica, velocidade diastólica, razão sístole/diástole e índice de resistência da artéria oftálmica.Conclusão: Foi observada centralização materna em gestações de alto risco em casos de hipertensão gestacional específica. Na curva normal, a média±desvio-padrão da relação sistólica/diastólica entre artéria uterina e artéria oftálmica foi de 0,43±0,16 (Doppler) para pacientes grávidas normais. Comparando-se o grupo de pacientes normais com o grupo de pacientes enfermas, houve diferença estatisticamente significativa entre grupos, considerando o estudo Doppler para a razão artéria uterina/artéria oftálmica.(...)

Angiogenic factors and uterine Doppler velocimetry in early- and late-onset preeclampsia.

OBJECTIVE: To assess correlations between maternal serum levels of pro- and anti-angiogenic factors with uterine perfusion in women with early- compared with late-onset preeclampsia, and in healthy pregnant women. DESIGN: Case-control study. SETTING: Antenatal care clinic located within a hospital (São Bernardo do Campo, Brazil). POPULATION: We enrolled 54 preeclamptic and 54 healthy control women who were coming for routine ultrasound at 28-36 weeks' gestation. METHODS: All participants had uterine artery and umbilical Doppler studies and a blood sample to assess maternal serum levels of soluble fms-like tyrosine kinase-1, soluble endoglin, adiponectin and plasminogen activator inhibitor-1. All angiogenic factors were measured using enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Levels of pro- and anti-angiogenic factors in maternal serum, and uterine artery Doppler findings. RESULTS: Concentrations of soluble fms-like tyrosine kinase-1 and soluble endoglin were significantly higher in preeclamptic than control women (p < 0.0001 and p < 0.0001, respectively), especially in those with early-onset (<34 weeks) preeclampsia. These two anti-angiogenic mediators were significantly correlated with increased uterine artery Doppler in the preeclamptic women. Plasminogen activator inhibitor-1 levels were significantly higher in preeclampsia (p = 0.03) but unrelated to uterine artery resistance. Adiponectin levels were similar in cases and controls, independent of body mass index and unrelated to uterine artery resistance. CONCLUSION: Preeclamptic patients have increased soluble fms-like tyrosine kinase-1 and soluble endoglin serum levels and this increase is directly correlated with uterine artery resistance, especially in those with early-onset preeclampsia.

Association of Doppler parameters with placental signs of underperfusion in late-onset small-for-gestational-age pregnancies.

OBJECTIVE: To elucidate the association between Doppler parameters and histological signs of placental underperfusion in late-onset small-for-gestational-age (SGA) babies. METHODS: Umbilical, fetal middle cerebral and uterine artery pulsatility indices and umbilical vein blood flow (UVBF), which had been recorded within 7 days prior to delivery, were analyzed from a cohort of SGA singleton pregnancies delivered after 34 weeks' gestation and confirmed as having a birth weight < 10(th) percentile by local standards. In each case, the placenta was histologically evaluated for signs of placental underperfusion using a hierarchical and standardized classification system. The independent association of the Doppler parameters with placental underperfusion was evaluated using logistic regression and decision tree analysis. RESULTS: In 51 cases (53.7%), there were 61 placental histological findings indicative of placental underperfusion. These cases had a significantly higher incidence of Cesarean section for non-reassuring fetal status (52.1% vs 11.9%; P < 0.001) and neonatal metabolic acidosis at birth (21.6% vs 0%; P = 0.001). Significant and independent contributions to the presence of placental underperfusion lesions were provided by increased mean UtA pulsatility index (PI) (P = 0.018; odds ratio (OR) 2 (95% CI, 1.1-3.7)) and decreased UVBF normalized to estimated fetal weight (P = 0.027; OR 0.97 (95% CI, 0.95-0.99)). The combination of both parameters revealed three groups with differing risks for placental underperfusion: normalized UVBF > 82 mL/min/kg (risk 31.3%), normalized UVBF ≤ 82 mL/min/kg and mean UtA-PI ≤ 95(th) percentile (risk 65.5%), and normalized UVBF ≤ 82 mL/min/kg and UtA-PI > 95(th) percentile (risk 94.4%). CONCLUSIONS: In late-onset SGA pregnancies, uterine Doppler and UVBF are surrogates for placental underperfusion. These findings facilitate phenotypic profiling of cases of fetal growth restriction among the general population of late-onset SGA babies.

Assessment of pregestational insulin resistance as a risk factor of preeclampsia.

AIM: To assess the impact that pregestational insulin resistance (PIR) has as a risk factor for preeclampsia (PE). METHODS: Nested case-control study that included patients with PIR and a control group that was randomly selected from pregnancies admitted to the Fetal Medicine Unit between January 2005 and May 2011. Clinical and hemodynamic variables were analyzed by a multiple logistic regression analysis. RESULTS: Of the 13,124 patients admitted during the study period, 119 had a diagnosis of PIR (0.9%). Patients with PIR were older and had a higher body mass index (BMI). PIR was also related to a significantly higher frequency of chronic hypertension (CrHT; 10.1 vs. 2.2%, p < 0.05) and hypothyroidism (5.0 vs. 1.6%, p < 0.05) than in the control group. Moreover, women with PIR were more likely to develop PE (8.4 vs. 4.2%, p < 0.05) and gestational diabetes mellitus (9.2 vs. 2.9%) than the control group. Multivariate analysis showed that maternal age, CrHT and altered uterine artery Doppler sonography during the first and second trimesters were good predictors of PE and that PIR was not. CONCLUSION: Although PIR correlates with PE, conditions related to the latter (CrHT, higher maternal age and increased BMI) may be predominant as risk factors for PE.

Função endotelial, perfusão uterina e fluxo central em gestações complicadas por Pré-Eclampsia / Endothelial function, uterine perfusion and central Flow in pregnancies complicated by Preeclampsia

FUNDAMENTO: A fisiopatologia da Pré-Eclampsia (PE) é caracterizada por deficiência no processo de placentação, disfunção endotelial sistêmica e hiperfluxo do Sistema Nervoso Central (SNC). Do ponto de vista clínico, seria interessante determinar a ocorrência desses fenômenos antes do aparecimento das manifestações clínicas da doença, levantando a possibilidade de novos métodos de predição da PE. OBJETIVO: Comparar o processo de placentação, a função endotelial e o hiperfluxo do SNC em gestantes de alto risco para desenvolvimento de PE que posteriormente desenvolveram ou não a síndrome. MÉTODOS: Um total de 74 gestantes foi submetido ao exame de Dilatação Fluxo-Mediada (DFM) da artéria braquial, dopplerfluxometria de artérias uterinas e oftálmica para avaliação da função endotelial, processo de placentação e hiperfluxo central, respectivamente. Os exames foram realizados entre 24 e 28 semanas de gestação e as pacientes foram acompanhadas até o puerpério para coleta de dados. RESULTADOS: Quinze pacientes tiveram a gestação complicada pela PE e 59 se mantiveram normotensas até o puerpério. Pacientes que subsequentemente desenvolveram PE apresentaram entre 24 e 28 semanas de gestação, maiores valores no índice de pulsatilidade das artérias uterinas e menores valores de DFM (p < 0,001 e p = 0,001, respectivamente). Entretanto, não houve diferença nos valores obtidos no índice de resistência da artéria oftálmica (p = 0,08). CONCLUSÃO: Os dados obtidos sugerem que a deficiência no processo de placentação e a disfunção endotelial precedem cronologicamente as manifestações clínicas da PE, o que não ocorre com o hiperfluxo do SNC.

BACKGROUND: The physiopathology of Preeclampsia (PE) is characterized by a deficiency in the process of placentation, systemic endothelial dysfunction and Central Nervous System (CNS) hyperflow. From a clinical point of view, it would be interesting to determine the occurrence of these phenomena before the onset of clinical manifestations of the disease, raising the possibility of new methods for predicting PE. OBJECTIVE:Compare the process of placentation, endothelial function and CNS hyperflow in pregnant women at high risk for the development of PE who subsequently developed or not the syndrome. METHODS: A total of 74 pregnant women underwent the Flow-Mediated Dilation (FMD) of the brachial artery, Doppler study of uterine and ophthalmic arteries for the assessment of endothelial function, process of placentation and central hyperflow, respectively. The examinations were performed between 24 and 28 weeks of gestation and were followed until the postpartum period for data collection. RESULTS: Fifteen patients had PE and 59 remained normotensive until the puerperium. Patients who subsequently developed PE had between 24 and 28 weeks of gestation, higher pulsatility index of uterine arteries and lower values of FMD (p < 0.001 and p = 0.001, respectively). However, there was no difference in the values obtained in the resistive index in the ophthalmic artery (p = 0.08). CONCLUSION: The data obtained suggest that the deficiency in the process of placentation and endothelial dysfunction chronologically precede the clinical manifestations of PE, which does not occur with CNS hyperflow.

Endothelial function, uterine perfusion and central flow in pregnancies complicated by Preeclampsia.

BACKGROUND: The physiopathology of Preeclampsia (PE) is characterized by a deficiency in the process of placentation, systemic endothelial dysfunction and Central Nervous System (CNS) hyperflow. From a clinical point of view, it would be interesting to determine the occurrence of these phenomena before the onset of clinical manifestations of the disease, raising the possibility of new methods for predicting PE. OBJECTIVE: Compare the process of placentation, endothelial function and CNS hyperflow in pregnant women at high risk for the development of PE who subsequently developed or not the syndrome. METHODS: A total of 74 pregnant women underwent the Flow-Mediated Dilation (FMD) of the brachial artery, Doppler study of uterine and ophthalmic arteries for the assessment of endothelial function, process of placentation and central hyperflow, respectively. The examinations were performed between 24 and 28 weeks of gestation and were followed until the postpartum period for data collection. RESULTS: Fifteen patients had PE and 59 remained normotensive until the puerperium. Patients who subsequently developed PE had between 24 and 28 weeks of gestation, higher pulsatility index of uterine arteries and lower values of FMD (p < 0.001 and p = 0.001, respectively). However, there was no difference in the values obtained in the resistive index in the ophthalmic artery (p = 0.08). CONCLUSION: The data obtained suggest that the deficiency in the process of placentation and endothelial dysfunction chronologically precede the clinical manifestations of PE, which does not occur with CNS hyperflow.

Reliability of examining the external iliac artery with Doppler ultrasound in the first trimester and its relationship with maternal blood pressure and uterine artery blood flow.

OBJECTIVE: To explore the reliability of examining the external iliac artery (EIA) at 11+0 to 13+6 weeks of gestation with Doppler ultrasound and its relationship with maternal characteristics and uterine artery blood flow. STUDY DESIGN: Cross-sectional study of 451 pregnant women undergoing an ultrasound scan in the first trimester. Mean pulsatility index (PI) of both EIAs was correlated to maternal characteristics (maternal age, parity, body mass index and mean arterial blood pressure (MAP)) and ultrasound parameters (crown-rump length (CRL) and mean uterine artery PI). Mean EIA-PI was logarithmically transformed to perform multiple linear regression analysis. The intra- and inter-observer reproducibilities of EIA-PI were examined. RESULTS: Satisfactory flow velocity waveforms were obtained from both EIA in all patients. There is a significant negative correlation between mean EIA pulsatility index and maternal blood pressure. Multiple linear regression analysis showed an independent contribution of MAP to log EIA-PI (mean) (standardized regression coefficient = -0.20, 95% CI: -0.005 to -0.002). The intra-class correlation coefficients (ICCs) for intraobserver and interobserver reproducibility were 0.94 (95% CI, 0.88-0.97) and 0.87 (0.76-0.94) respectively. CONCLUSIONS: Examining blood flow in the external iliac artery using Doppler ultrasound in the first trimester is feasible and reproducible. There is a negative correlation between mean EIA-PI and maternal blood pressure.

[Uterine artery score in patients with systemic lupus erythematous as a predictor of intrauterine growth restriction]. / Indice de arterias uterinas en pacientes con lupus eritematoso sistémico como predictor de restricción del crecimiento intrauterino.

BACKGROUND: Because of its high prevalence in the female population and its high incidence in reproductive age, Systemic Lupus Erythematosus can complicate pregnancy causing miscarriage, fetal death, preeclampsia, fetal growth restriction (up to 25%) and preterm birth. Doppler ultrasonography measures the flow in the uterine arteries, which is reduced in patients with preeclampsia and FGR, and thus is an ideal method for identifying pregnant women with a high risk of developing an adverse perinatal outcome. OBJECTIVE: Identify if Doppler ultrasound predicts FGR in patients with systemic lupus erythematosus. PATIENTS AND METHOD: In this observational, transversal, prospective study carried out from June 1st, 2010 to November 30th, 2010, in patients who had already been diagnosed with SLE, a complete clinical history was registered, blood samples taken and Doppler of uterine arteries between 18 and 23 gestation weeks taken (measuring the pulsatility index) RESULTS: Of the 17 women in the study, 6 patients had a PI equal or greater than 1.45 (35.29%), of whom in 5 cases (29.41%), the product had FGR. Therefore the sensitivity of this test is 100%, with a specificity of 91%, a predictive positive value of 83% and a predictive negative value of 100%. With a p of 0.0010, which is considered extremely significant, and a confidence interval of 95%. CONCLUSIONS: There exists a high association between an abnormal PI and the development of FGR. Abnormal Doppler ultrasound of uterine arteries is useful for predicting FGR in pregnant women with SLE.

High-end arteriolar resistance limits uterine artery blood flow and restricts fetal growth in preeclampsia and gestational hypertension at high altitude.

The reduction in infant birth weight and increased frequency of preeclampsia (PE) in high-altitude residents have been attributed to greater placental hypoxia, smaller uterine artery (UA) diameter, and lower UA blood flow (Q(UA)). This cross-sectional case-control study determined UA, common iliac (CI), and external iliac (EI) arterial blood flow in Andeans residing at 3,600-4,100 m, who were either nonpregnant (NP, n = 23), or experiencing normotensive pregnancies (NORM; n = 155), preeclampsia (PE, n = 20), or gestational hypertension (GH, n = 12). Pregnancy enlarged UA diameter to ~0.62 cm in all groups, but indices of end-arteriolar vascular resistance were higher in PE or GH than in NORM. Q(UA) was lower in early-onset (≤34 wk) PE or GH than in NORM, but was normal in late-onset (>34 wk) illness. Left Q(UA) was consistently greater than right in NORM, but the pattern reversed in PE. Although Q(CI) and Q(EI) were higher in PE and GH than NORM, the fraction of Q(CI) distributed to the UA was reduced 2- to 3-fold. Women with early-onset PE delivered preterm, and 43% had stillborn small for gestational age (SGA) babies. Those with GH and late-onset PE delivered at term but had higher frequencies of SGA babies (GH=50%, PE=46% vs. NORM=15%, both P < 0.01). Birth weight was strongly associated with reduced Q(UA) (R(2) = 0.80, P < 0.01), as were disease severity and adverse fetal outcomes. We concluded that high end-arteriolar resistance, not smaller UA diameter, limited Q(UA) and restricted fetal growth in PE and GH. These are, to our knowledge, the first quantitative measurements of Q(UA) and pelvic blood flow in early- vs. late-onset PE in high-altitude residents.