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Preeclampsia (PE) is a specific syndrome of pregnancy, characterized by hypertension and proteinuria. This pathology is associated with hyperuricemia and elevated serum levels of inflammatory cytokines. Uric acid crystals may activate an intracellular complex called inflammasome, which is important for processing and release of inflammatory cytokines. This study investigated the state of monocyte activation, both endogenous and stimulated with monosodium urate (MSU), by gene expression of NLRP1 and NLRP3 receptors as well as their association with inflammatory cytokines expression. Monocytes were obtained from peripheral blood of 23 preeclamptic pregnant women, 23 normotensive pregnant women (NT) and 23 healthy non-pregnant women (NP). Inflammasome activation was evaluated by the gene expression of NLRP1, NLRP3, caspase-1, IL-1β, IL-18 and TNF-α by RT-qPCR in unstimulated monocytes (endogenous expression), or after cell stimulation with MSU (stimulated expression). The concentration of cytokines was assessed by ELISA. In preeclamptic pregnant women, gene expression of NLRP1, NLRP3, caspase-1, IL-1β and TNF-α by monocytes stimulated or not with MSU was significantly higher than in NT and NP groups. Stimulation of monocytes from preeclamptic and non-pregnant women with MSU induced increased gene expression of NLRP3, caspase-1 and TNF-α in relation to the endogenous expression in these groups, while this was not observed in the NT group. The cytokine determination showed that monocytes from women with PE produced higher endogenous levels of IL-1β, IL-18 and TNF-α compared to the other groups, while the stimulus with MSU led to higher production of these cytokines in preeclamptic group than in the NT group. In conclusion, the results showed increased basal gene expression of NLRP1 and NLRP3 receptors in monocytes from PE group. These cells stimulation with MSU demonstrates that uric acid plays a role in NLRP3 inflammasome activation, suggesting the participation of this inflammatory complex in the pathogenesis of preeclampsia.

This study aimed to evaluate the levels of pro- and anti-inflammatory cytokines in umbilical cord blood of preterm neonates who developed focal early-onset infection (EOI) after preterm premature rupture of membranes (PPROM). This is a prospective study conducted on 46 preterm infants from mothers with PPROM. The cytokines were measure by flow cytometry. Newborns were classified into two groups as focal EOI (n=19) and non-infected (n=27). Interleukin (IL)-6 and IL-8 levels were higher, whereas IL-10 and IL-12 p70 levels were lower in the EOI when compared to the non-infected group. The best combination of cytokines was IL-6+IL-8, with a diagnostic accuracy of 0.97. Focal EOI after PPROM is associated with increased levels of IL-6 and IL-8 and diminished IL-10 and IL-12 in the cord blood of preterm infants. Combined assessment of IL-6 and IL-8 in cord blood may provide an additional tool for identifying preterm infants who develop EOI after PPROM.

Background Pregnant women with mild gestational hyperglycemia present high risk for hypertension, obesity and hyperglycemia, and appeared to reproduce the model of metabolic syndrome in pregnancy, with hyperinsulinemia and insulin resistance. Our clinical studies showed that mild gestational hyperglycemia or gestational diabetes are related to similar adverse maternal and perinatal outcomes. Hyperglycemia and other factors associated with diabetes generate reactive oxygen species that increase DNA damage levels. The aim of this study was to evaluate oxidative DNA damage in lymphocytes of pregnant women with diabetes or mild gestational hyperglycemia. Methods The study included 111 pregnant women distributed into three groups based on oral glucose tolerance test (OGTT) and glycemic profiles (GP), as follows: Normal OGTT and GP (control group); Normal OGTT and abnormal GP (mild gestational hyperglycemia group); Abnormal OGTT and GP (diabetic group). Maternal blood samples (5–10 mL) were collected and processed for determination of oxidative DNA damage by the comet assay, using Fpg and Endo III enzymes. Urine samples were also collected for determination of 8-OHdG concentrations by ELISA. Results Subjects in the diabetes group presented increased amount of oxidized purines, while mild gestational hyperglycemia women presented with increased oxidized pyrimidines, compared to the control group. Conclusion Gestational, overt diabetes and mild gestational hyperglycemia, were all related to increased oxidative DNA damage. Diabetic pregnant women showed increased level of oxidative DNA damage, perhaps mainly due to hyperglycemia. On the other hand, oxidative DNA damage detected in women with mild gestational hyperglycemia might be associated with repercussions from obesity, hypertension and/or insulin resistance. Interestingly, the type of DNA base affected seemed to be dependent on the glycemic profile or oxidative stress.

BACKGROUND Pregnancy and arterial hypertension (AH) have a prohypertrophic effect on the heart. It is suspected that the 2 conditions combined cause disproportionate myocardial hypertrophy. We sought to evaluate myocardial hypertrophy (LVH) and left ventricular function in normotensive and hypertensive women in the presence or absence of pregnancy. METHODS This prospective cross-sectional study included 193 women divided into 4 groups: hypertensive pregnant (HTP; n = 57), normotensive pregnant (NTP; n = 47), hypertensive nonpregnant (HTNP; n = 41), and normotensive nonpregnant (NTNP; n = 48). After clinical and echocardiographic evaluation, the variables were analyzed using 2-way analysis of variance with pregnancy and hypertension as factors. Left ventricular mass (LVM) was compared using nonparametric analysis of variance and Dunn′s test. Predictors of LVH and diastolic dysfunction were analyzed using logistic regression (significance level, P < 0.05). RESULTS Myocardial hypertrophy was independently associated with hypertension (odds ratio (OR) = 11.1, 95% confidence interval (CI) = 3.2-38.5; P < 0.001) and pregnancy (OR = 6.1, 95% CI = 2.6-14.3; P < 0.001) in a model adjusted for age and body mass index. Nonpregnant women were at greater risk of LVH in the presence of AH (OR = 25.3, 95% CI = 3.15-203.5; P = 0.002). The risk was additionally increased in hypertensive women during pregnancy (OR = 4.3, 95% CI = 1.7-10.9; P = 0.002) in the model adjusted for stroke volume and antihypertensive medication. Although none of the NTNP women presented with diastolic dysfunction, it was observed in 2% of the NTP women, 29% of the HTNP women, and 42% of the HTP women (P < 0.05). CONCLUSIONS Hypertension and pregnancy have a synergistic effect on ventricular remodeling, which elevates a woman's risk of myocardial hypertrophy.

Background According to the World Health Organization, there are over 6.3 million perinatal deaths (PND) a year worldwide. Identifying the factors associated with PND is very helpful in building strategies to improve the care provided to mothers and their babies. Objective To investigate the maternal, gestational and neonatal factors associated with PND at two different levels of care. Methods Case–control study including 299 PND cases and 1161 infants that survived the early neonatal period (controls) between 2001–2006 in two hospitals at different care levels (secondary and tertiary) located in southeastern Brazil. Correlations between study variables and PND were evaluated by univariate analysis. PND-related variables were included in a multiple logistic regression model, and independent estimates of PND risk were obtained. Results Although five-minute Apgar score <7, low birthweight and maternal hemorrhage were associated with PND in the secondary care center, no independent risk factors were identified at this level of care. In the tertiary hospital, PND was positively associated with primiparity, male sex, prematurity, low 5-minute Apgar score, and pregnancy complicated by arterial hypertension or intrauterine infection. Conclusions Several risk factors positively associated with PND were indentified in the tertiary, but not in the secondary care level hospital. Since most of the risk factors herein identified are modifiable through effective antenatal and intrapartum care, greater attention should be given to preventive strategies.

Preeclampsia (PE) is a human pregnancy-specific syndrome with abnormal activation of cells from the innate immune system. The present study evaluated whether silibinin (SB) treatment of monocytes from preeclamptic women could modulate NLRP1 and NLRP3 inflammasomes as well as TLR4/NF-κB pathway activation. Peripheral blood monocytes from 20 preeclamptic and 20 normotensive (NT) pregnant women, as well as the THP-1 cell line, were cultured with or without monosodium urate (MSU) or SB. NLRP1, NLRP3, Caspase-1, TLR4, MyD88, NF-κB, IL-1β, IL-18, TNF-α and IL-10 gene expression by monocytes was analysed by quantitative real-time polymerase chain reaction (qPCR), while inflammatory cytokine production and p65NF-κB activity were determined by enzyme-linked immunosorbent assays (ELISAs). TLR4/MyD88/NF-κB and NLRP1/NLRP3 inflammasomes pathways in THP-1 cells were evaluated by flow cytometry and western blot respectively. Compared with NT women, monocytes from preeclamptic women showed The Ethics Committee of the Botucatu Medical School approved the study (protocol number 2.333.216)higher endogenous activation of NLRP1/NLRP3 inflammasomes and the TLR4/NF-κB pathway as well as higher gene and protein expression of IL-1β, IL-18 and TNF-α, and lower expression of IL-10. Monocyte stimulation with MSU increased inflammation-related genes as well as NF-κB activity. In vitro, SB treatment of monocytes from preeclamptic women reduced the basal activation of these cells by decreasing NLRP1/NLRP3 inflammasomes and p65NF-κB activity. THP-1 cells exhibited a similar immunological response profile to monocytes from preeclamptic women when cultured with or without MSU or SB. These results suggest uric acid participates in the systemic inflammatory response characteristic of preeclampsia and that in vitro SB treatment can modulate the sterile inflammation established in monocytes from preeclamptic women.

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.

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.

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.