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Preeclampsia (PE) is considered the leading cause of maternal and perinatal morbidity and mortality. The placenta seems to play an essential role in this disease, probably due to factors involved in its formation and development. The present study aimed to investigate the association between placental lesions, cytokines and angiogenic factors in pregnant women with preeclampsia (PE). We evaluated 20 normotensive pregnant women, 40 with early-onset PE and 80 with late-onset PE. Placental samples were analyzed for histopathology, immunohistochemistry and determination of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-10 (IL-10), transforming growth factor-beta 1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), placental growth factor (PlGF), vascular endothelial growth factor (VEGF), fms-like tyrosine-kinase-1 (Flt-1) and endoglin (Eng) levels. Higher percentages of increased syncytial knots and increased perivillous fibrin deposits, and greater levels of TNF-α, TGF-β1and Flt-1 were detected in placentas from early-onset PE. Levels of IL-10, VEGF and PlGF were decreased in PE versus normotensive placentas. Both the TNF-α/IL-10 and sFlt-1/PlGF ratios were higher in placental homogenate of early-onset PE than late-onset PE and control groups. The more severe lesions and the imbalance between TNF-α/IL-10 and PlGF/sFlt-1 in placentas from early-onset PE allows differentiation of early and late-onset PE and suggests higher placental impairment in early-onset PE.

Purpose To assess the association between maternal potentially life-threatening conditions (PLTC), maternal near miss (MNM), and maternal death (MD) with perinatal outcomes. Methods Cross-sectional study in 27 Brazilian referral centers from July, 2009 to June, 2010. All women presenting any criteria for PLTC and MNM, or MD, were included. Sociodemographic and obstetric characteristics were evaluated in each group of maternal outcomes. Childbirth and maternal morbidity data were related to perinatal adverse outcomes (5th min Apgar score < 7, fetal death, neonatal death, or any of these). The Chi-squared test evaluated the differences between groups. Multiple regression analysis adjusted for the clustering design effect identified the independently associated maternal factors with the adverse perinatal outcomes (prevalence ratios; 95% confidence interval). Results Among 8271 cases of severe maternal morbidity, there were 714 cases of adverse perinatal outcomes. Advanced maternal age, low level of schooling, multiparity, lack of prenatal care, delays in care, preterm birth, and adverse perinatal outcomes were more common among MNM and MD. Both MNM and MD were associated with Apgar score (2.39; 1.68–3.39); maternal hemorrhage was the most prevalent characteristic associated with fetal death (2.9, 95% CI 1.81–4.66) and any adverse perinatal outcome (2.16; 1.59–2.94); while clinical/surgical conditions were more related to neonatal death (1.56; 1.08–2.25). Conclusion We confirmed the association between MNM and MD with adverse perinatal outcomes. Maternal and perinatal issues should not be dissociated. Policies aiming maternal care should include social and economic development, and improvements in accessibility to specialized care. These, in turn, will definitively impact on childhood mortality rates.

Hypertensive disorders of pregnancy (HDP), comprising gestational hypertension (GH) and pre-eclampsia (PE), are leading causes of maternal and perinatal morbidity and mortality. Both GH and PE are characterized by new-onset hypertension, but PE additionally includes proteinuria and/or end-organ damage. Impaired nitric oxide (NO) bioavailability may lead to endothelial dysfunction in GH and PE, and the primary source of vascular NO is endothelial NO synthase (eNOS). However, no previous study has investigated plasma eNOS concentrations in patients with GH and PE. In this study, we compared plasma eNOS concentrations in healthy pregnancies and HDP in two independent cohorts. The primary study included 417 subjects, with 43 non-pregnant (NP) and 156 healthy pregnant (HP) women and 122 patients with GH and 96 with PE. The replication study included 85 pregnant women (41 healthy and 44 pre-eclamptic). Plasma concentrations of eNOS were measured using a commercial ELISA kit provided by R&D Systems, and plasma nitrite concentrations were assessed using two ozone-based chemiluminescence assays. Correlations between plasma eNOS concentrations and plasma nitrite concentrations, as well as clinical and biochemical parameters, were evaluated by either Spearman’s or Pearson’s tests. In the primary study, NP women and HDP had significantly lower plasma eNOS concentrations compared to HP; concentrations were even lower in PE compared to GH. Plasma eNOS concentrations were reduced but not significant in early-onset PE, PE with severe features, preterm birth, and intrauterine growth restriction. No correlation was observed between plasma eNOS and nitrite levels. In HDP, there was a significant positive correlation between levels of eNOS and hemoglobin (r = 0.1496, p = 0.0336) as well as newborn weight (r = 0.1487, p = 0.0316). Conversely, a negative correlation between eNOS levels and proteinuria was observed (r = −0.2167, p = 0.0179). The replication study confirmed significantly reduced plasma concentrations of eNOS in PE compared to HP. Our findings provide evidence of reduced plasma eNOS concentrations in HDP; they were particularly lower in PE compared to GH and HP in two independent studies.

Objective. To assess quality of care of women with severe maternal morbidity and to identify associated factors. Method. This is a national multicenter cross-sectional study performing surveillance for severe maternal morbidity, using the World Health Organization criteria. The expected number of maternal deaths was calculated with the maternal severity index (MSI) based on the severity of complication, and the standardized mortality ratio (SMR) for each center was estimated. Analyses on the adequacy of care were performed. Results. 17 hospitals were classified as providing adequate and 10 as nonadequate care. Besides almost twofold increase in maternal mortality ratio, the main factors associated with nonadequate performance were geographic difficulty in accessing health services (P<0.001), delays related to quality of medical care (P=0.012), absence of blood derivatives (P=0.013), difficulties of communication between health services (P=0.004), and any delay during the whole process (P=0.039). Conclusions. This is an example of how evaluation of the performance of health services is possible, using a benchmarking tool specific to Obstetrics. In this study the MSI was a useful tool for identifying differences in maternal mortality ratios and factors associated with nonadequate performance of care.

Preeclampsia (PE) is a pregnancy-specific syndrome characterized by a systemic inflammatory response that polarizes peripheral blood monocytes to the M1 phenotype. The classically activated M1 monocytes comprise immune effector cells with an acute inflammatory phenotype. CD163 is a scavenger receptor expressed by monocytes/macrophages that may be shed from their cell membrane after proteolytic cleavage, producing the soluble CD163 molecule (sCD163). This study evaluated CD163 expression by monocytes and sCD163 as well as pro- and anti-inflammatory cytokine concentration in the plasma of pregnant women with PE. Fifty-six women with PE and 28 normotensive pregnant women were included. Plasma levels of sCD163, interleukin-1 beta (IL-1β), IL-6, IL-10, transforming growth factor beta (TGF-β1), and tumor necrosis factor-alpha (TNF-α) were determined by ELISA, and CD163 expression by monocytes was assessed by flow cytometry. The expression of CD163 by monocytes was significantly lower in severe and mild PE than in normotensive pregnant. Plasma concentrations of IL-1β, TGF-β1, and TNF-α were higher in severe PE than in mild PE and normotensive pregnant women. Both groups of preeclamptic women showed decreased plasma levels of sCD163 and IL-10. Negative correlations between sCD163 and IL-1β (r = − 0.45; P = 0.014) and between sCD163 and TNF-α concentrations (r = − 0.54; P = 0.001) were observed in the severe PE group. The association between the pro-inflammatory cytokine profile and lower concentrations of sCD163 and IL-10 in plasma from women with severe PE suggests an impairment in the modulation of the systemic inflammatory response in this group of pregnant women with preeclampsia.

Background:To evaluate associations between alterations in vaginal flora and clinical symptoms in low-risk pregnant women. Methods:Vaginal specimens from 245 pregnant women were analyzed by microscopy for vaginal flora. Signs and symptoms of vaginal infection were determined by patient interviews and gynecologic examinations. Results:Abnormal vaginal flora was identified in 45.7% of the subjects. The final clinical diagnoses were bacterial vaginosis (21.6%), vaginal candidosis (10.2%), intermediate vaginal flora (5.2%), aerobic vaginitis (2.9%), mixed flora (2.9%) and other abnormal findings (2.9%). The percentage of women with or without clinical signs or symptoms was not significantly different between these categories. The presence of vaginal odor or vaginal discharge characteristics was not diagnostic of any specific flora alteration; pruritus was highly associated with candidosis (p < 0.0001). Compared to women with normal flora, pruritus was more prevalent in women with candidosis (p < 0.0001), while vaginal odor was associated with bacterial vaginosis (p = 0.0026). Conclusion:The prevalence of atypical vaginal flora is common in our low-risk pregnant population and is not always associated with pathology. The occurrence of specific signs or symptoms does not always discriminate between women with different types of atypical vaginal flora or between those with abnormal and normal vaginal flora.

Background In 2000, the eight Millennium Development Goals (MDGs) set targets for reducing child mortality and improving maternal health by 2015. Objective To evaluate the results of a new education and referral system for antenatal/intrapartum care as a strategy to reduce the rates of Cesarean sections (C-sections) and maternal/perinatal mortality. Methods Design : Cross-sectional study. Setting : Department of Gynecology and Obstetrics, Botucatu Medical School, Sao Paulo State University/UNESP, Brazil. Population : 27,387 delivering women and 27,827 offspring. Data collection : maternal and perinatal data between 1995 and 2006 at the major level III and level II hospitals in Botucatu, Brazil following initiation of a safe motherhood education and referral system. Main outcome measures : Yearly rates of C-sections, maternal (/100,000 LB) and perinatal (/1000 births) mortality rates at both hospitals. Data analysis : Simple linear regression models were adjusted to estimate the referral system's annual effects on the total number of deliveries, C-section and perinatal mortality ratios in the two hospitals. The linear regression were assessed by residual analysis (Shapiro-Wilk test) and the influence of possible conflicting observations was evaluated by a diagnostic test (Leverage), with p < 0.05. Results Over the time period evaluated, the overall C-section rate was 37.3%, there were 30 maternal deaths (maternal mortality ratio = 109.5/100,000 LB) and 660 perinatal deaths (perinatal mortality rate = 23.7/1000 births). The C-section rate decreased from 46.5% to 23.4% at the level II hospital while remaining unchanged at the level III hospital. The perinatal mortality rate decreased from 9.71 to 1.66/1000 births and from 60.8 to 39.6/1000 births at the level II and level III hospital, respectively. Maternal mortality ratios were 16.3/100,000 LB and 185.1/100,000 LB at the level II and level III hospitals. There was a shift from direct to indirect causes of maternal mortality. Conclusions This safe motherhood referral system was a good strategy in reducing perinatal mortality and direct causes of maternal mortality and decreasing the overall rate of C-sections.

Background The vast majority of maternal deaths in low-and middle-income countries are preventable. Delay in obtaining access to appropriate health care is a fairly common problem which can be improved. The objective of this study was to explore the association between delay in providing obstetric health care and severe maternal morbidity/death. Methods This was a multicentre cross-sectional study, involving 27 referral obstetric facilities in all Brazilian regions between 2009 and 2010. All women admitted to the hospital with a pregnancy-related cause were screened, searching for potentially life-threatening conditions (PLTC), maternal death (MD) and maternal near-miss (MNM) cases, according to the WHO criteria. Data on delays were collected by medical chart review and interview with the medical staff. The prevalence of the three different types of delays was estimated according to the level of care and outcome of the complication. For factors associated with any delay, the PR and 95%CI controlled for cluster design were estimated. Results A total of 82,144 live births were screened, with 9,555 PLTC, MNM or MD cases prospectively identified. Overall, any type of delay was observed in 53.8% of cases; delay related to user factors was observed in 10.2%, 34.6% of delays were related to health service accessibility and 25.7% were related to quality of medical care. The occurrence of any delay was associated with increasing severity of maternal outcome: 52% in PLTC, 68.4% in MNM and 84.1% in MD. Conclusions Although this was not a population-based study and the results could not be generalized, there was a very clear and significant association between frequency of delay and severity of outcome, suggesting that timely and proper management are related to survival.

To validate the WHO maternal near-miss criteria and develop a benchmark tool for severe maternal morbidity assessments. In a multicenter cross-sectional study implemented in 27 referral maternity hospitals in Brazil, a one-year prospective surveillance on severe maternal morbidity and data collection was carried out. Diagnostic accuracy tests were used to assess the validity of the WHO maternal near-miss criteria. Binary logistic regression was used to model the death probability among women with severe maternal complications and benchmark the management of severe maternal morbidity. Of the 82,388 women having deliveries in the participating health facilities, 9,555 women presented pregnancy-related complications, including 140 maternal deaths and 770 maternal near misses. The WHO maternal near-miss criteria were found to be accurate and highly associated with maternal deaths (Positive likelihood ratio 106.8 (95% CI 99.56-114.6)). The maternal severity index (MSI) model was developed and found to able to describe the relationship between life-threatening conditions and mortality (Area under the ROC curve: 0.951 (95% CI 0.909-0.993)). The identification of maternal near-miss cases using the WHO list of pregnancy-related life-threatening conditions was validated. The MSI model can be used as a tool for benchmarking the performance of health services managing women with severe maternal complications and provide case-mix adjustment.

Background The aim of this study was to assess severe maternal morbidity (SMM) and near miss (NM) cases among adolescent girls and women over 35 years of age in the Brazilian Network for Surveillance of Severe Maternal Morbidity, using a set of standard criteria, compared to pregnant women aged 20 to 34 years. Methods A cross-sectional multicenter study conducted in 27 referral obstetric units in Brazil. All pregnant women admitted to these centers during a one-year period of prospective surveillance were screened to identify cases of maternal death (MD), NM and other SMM . Indicators of maternal morbidity and mortality were evaluated for the three age groups. Sociodemographic, clinical and obstetric characteristics, gestational and perinatal outcomes, main causes of morbidity and delays in care were also compared. Two multiple analysis models were performed, to estimate the adjusted prevalence ratio for identified factors that were independently associated with the occurrence of severe maternal outcome (SMO = MNM + MD). Results Among SMM and MD cases identified, the proportion of adolescent girls and older women were 17% each. The risk of MNM or death was 25% higher among older women. Maternal near miss ratio and maternal mortality ratios increased with age, but these ratios were also higher among adolescents aged 10 to 14, although the absolute numbers were low. On multivariate analysis, younger age was not identified as an independent risk factor for SMO, while this was true for older age (PR 1.25; 1.07-1.45). Conclusions SMO was high among women below 14 years of age and increased with age in Brazilian pregnant women.