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The aim was to assess the role of Metabolic Syndrome (MetS) diagnostic markers, recommended by three different guidelines, in the prediction of hyperglycemia in pregnancy. This cross-sectional cohort study included 506 non-diabetic women, with a singleton pregnancy, who underwent a diagnostic test for hyperglycemia at 24-28 weeks. Clinical, anthropometric, and laboratory data were obtained. The relationship between MetS markers and the risk of hyperglycemia was evaluated by backward stepwise logistic regression analysis (OR, 95% CI). The limit of statistical significance was 95% (p < 0.05). Triglycerides (TG) ≥ 150 mg/dL, blood pressure (BP) ≥ 130/85 mmHg, fasting glucose (FG) ≥ 100 mg/dL, and waist circumference (WC) > 88 cm were identified as independent risk factors for hyperglycemia in pregnancy. These results might help the selective screening of hyperglycemia in pregnancy.

Background: Pelvic floor muscles (PFM) and rectus abdominis muscles (RAM) of pregnant diabetic rats exhibit atrophy, co-localization of fast and slow fibers and an increased collagen type I/III ratio. However, the role of similar PFM or RAM hyperglycemic-related myopathy in women with gestational diabetes mellitus (GDM) remains poorly investigated. This study aims to assess the frequency of pelvic floor muscle disorders and pregnancy-specific urinary incontinence (PS-UI) 12 months after the Cesarean (C) section in women with GDM. Specifically, differences in PFM/RAM hyperglycemic myopathy will be evaluated., Methods: The Diamater is an ongoing cohort study of four groups of 59 pregnant women each from the Perinatal Diabetes Research Centre (PDRC), Botucatu Medical School (FMB)-UNESP (São Paulo State University), Brazil. Diagnosis of GDM and PS-UI will be made at 24-26 weeks, with a follow-up at 34-38 weeks of gestation. Inclusion in the study will occur at the time of C-section, and patients will be followed at 24-48 h, 6 weeks and 6 and 12 months postpartum. Study groups will be classified as (1) GDM plus PS-UI; (2) GDM without PS-UI; (3) Non-GDM plus PS-UI; and (4) Non-GDM without PS-UI. We will analyze relationships between GDM, PS-UI and hyperglycemic myopathy at 12 months after C-section. The mediator variables to be evaluated include digital palpation, vaginal squeeze pressure, 3D pelvic floor ultrasound, and 3D RAM ultrasound. RAM samples obtained during C-section will be analyzed for ex-vivo contractility, morphological, molecular and OMICS profiles to further characterize the hyperglycemic myopathy. Additional variables to be evaluated include maternal age, socioeconomic status, educational level, ethnicity, body mass index, weight gain during pregnancy, quality of glycemic control and insulin therapy., Discussion: To our knowledge, this will be the first study to provide data on the prevalence of PS-UI and RAM and PFM physical and biomolecular muscle profiles after C-section in mothers with GDM. The longitudinal design allows for the assessment of cause-effect relationships between GDM, PS-UI, and PFMs and RAMs myopathy. The findings may reveal previously undetermined consequences of GDM.

Aims: To estimate and compare the alterations in the urethral tissues of female rats with two diabetes models: short-term severe and long-term mild diabetes., Methods: To induce mild diabetes (blood glucose levels between 120 and 300 mg/dl), female newborns received streptozotocin (100 mg/kg body weight, sc route), and to induce short-term severe diabetes (blood glucose levels > 300 mg/d), adult animals received streptozotocin (40 mg/kg, iv route). The rats were killed on day 133 of the experimental via an i.p. Thiopentax ® injection of 80 mg/kg, and the urethrovaginal tissues were harvested. Morphometric, pathological, immunohistochemical, and ultrastructural analyses were conducted., Results: In the long-term mild diabetes group, collagen deposition, severe fibrosis, lipid droplets and numerous subsarcolemmal, and intermyofibrillar mitochondria were observed. In the short-term severe diabetes group, centrally located myonuclei and a significantly reduced striated muscle area were noted. Both diabetic models exhibited similar immunohistochemistry patterns, with changes from fast to slow fibers and a decrease in the numbers of fast fibers., Conclusions: Either long-term mild hyperglycemia or short-term severe hyperglycemia have detrimental impacts on muscle health. They are both involved in the failure to maintain healthy skeletal muscle that may contribute to the development of pelvic floor dysfunctions via different pathways. These results have important implications for monitoring and prevention strategies for improving the quality of life of women with diabetes mellitus and pelvic floor muscle dysfunction. Neurourol. Urodynam. 36:574-579, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Introduction: Gestational (GC) (derived from the placenta) and non-gestational (NGC) choriocarcinomas are trophoblastic diseases originated from abnormal proliferation of trophoblastic cells. These rare tumors share similar morphology and pathological features and differ on chemotherapy response, genetic origin and prognosis. In this study, the genomic profile of choriocarcinomas was performed according to their origin (GC or NGC) aiming to better understand these poorly characterized diseases., Methods: Thirteen patients were included in this study; 10 presented previous history of hydatidiform mole and six developed metastasis. Twelve polymorphic microsatellite markers (D15S659, APOC2, D5S816, BAT25, D3S1614, D3S1311, D1S1656, APC-D5S346, D3S1601, D18S70, D8S1110 and D11S1999) were investigated to distinguish GC from NGC. All choriocarcinomas were evaluated by copy number alterations using array CGH., Results: Eight cases were classified as GC and five as NGC. Although potentially polymorphic, NGC exhibited significant gain of 21p11. Rare copy number alterations (CNA) were detected as a frequent event in GC including gains of 1p36.33-p36.32 (3 cases), 17q25.3 (4 cases), and losses of 9q33.1 (5 cases), 17q21.3 (3 cases) and 18q22.1 (4 cases) (varying from 724 to 3,053 Kb)., Discussion: Two tumor suppressor genes are candidates to be involved in GC: TRIM32 (9q33.1) and CDH19 (18q22.1). Gains of CBX2, CBX4 and CBX8 were frequently found in high risk prognostic score in GC. The in silico functional interaction analysis revealed the involvement of PTEN and PI3K-Akt signaling pathways. These data pointed out significant genomic alterations in GC, opening new avenues to better characterize the pathobiology of this disease., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: In August 2011, the Specialized Center for Diabetes and Pregnancy of the Botucatu Medical School/Unesp adopted a new diagnostic protocol for gestational diabetes mellitus, recommended by the American Diabetes Association and the International Association of the Diabetes and Pregnancy Study Group. The glycemic profile was evaluated using the 75-g oral glucose tolerance test (OGTT) used to diagnose mild gestational hyperglycemia, recognized and treated in our department as gestational diabetes mellitus. The cost-effectiveness of the new guidelines and the continued need for the evaluation of the glycemic profile, as part of our Service protocol, are controversial and require further investigation. We aimed to assess the impact of the new guidelines on the evaluation of mild gestational hyperglycemia and gestational diabetes mellitus, the incidence of adverse perinatal outcomes, and the association between the 75-g OGTT and the glycemic profile for the diagnosis of mild gestational hyperglycemia., Methods: This cross-sectional study was performed identifying a convenience sample of pregnant women and their newborns. The women used our Service for diagnostic procedures, prenatal care and delivery, both before (January 2008 to August 14, 2011) and after (August 15, 2011 to December 2014) the protocol modification. The following variables were compared, following stratification according to diagnostic protocol: prevalence of gestational diabetes mellitus and mild gestational hyperglycemia, newborns large for gestational age, macrosomia, first cesarean delivery, and newborn hospital stay. Statistical analysis was performed using Poisson regression, the Student's t test, the Chi square or Fisher's exact test and risk estimate. The statistical significance threshold was set at 95% (p < 0.05)., Results: The new protocol resulted in an 85% increase in the number of women with GDM, but failed to identify 17.3% of pregnant women classified as having mild gestational hyperglycemia, despite a normal 75-g OGTT. The new guidelines did not affect perinatal outcome., Conclusions: These results support the validity of maintaining the glycemic profile as part of the diagnostic protocol at our hospital. Large multicenter studies with an adequate sample size are required for conclusive evidence on the cost-effectiveness of the new protocol.

Objective: To evaluate the gene expression profile of whole blood cells in pregnant women without diabetes (with positive screening and negative diagnosis for gestational diabetes mellitus (GDM)) compared with pregnant women with negative screening for GDM., Research Design and Methods: Pregnant women were recruited in the Diabetes Perinatal Research Centre-Botucatu Medical School-UNESP and Botucatuense Mercy Hospital (UNIMED). Distributed into 2 groups: control (n=8), women with negative screening and non-diabetic (ND, n=13), with positive screening and negative diagnosis of GDM. A peripheral blood sample was collected for glucose, glycated hemoglobin, and microarray gene expression analyses., Results: The evaluation of gene expression profiles showed significant differences between the control group and the ND group, with 22 differentially expressed gene sequences. Gene networks and interaction tables were generated to evaluate the biological processes associated with differentially expressed genes of interest., Conclusions: In the group with positive screening, there is an apparent regulatory balance between the functions of the differentially expressed genes related to the pathogenesis of diabetes and a compensatory attempt to mitigate the possible etiology. These results support the 'two-step Carpenter-Coustan' strategy because pregnant women with negative screening do not need to continue on diagnostic investigation of gestational diabetes, thus reducing the cost of healthcare and the medicalization of pregnancy. Although not diabetic, they do have risk factors, and thus attention to these genes is important when considering disease evolution because this pregnant women are a step toward developing diabetes compared with women without these risk factors., Competing Interests: Conflicts of Interest: None declared.

Background: Maternal obesity is associated with several adverse pregnancy outcomes. This study was conducted aiming to evaluate maternal levels of adipokines and insulin in pregnancies complicated by overweight and obesity and its correlations with maternal and fetal outcomes., Methods: This cross-sectional study included 72 mother-newborn pairs. Mothers were classified as having normal weight (n = 23), overweight (n = 18), and obesity (n = 31). Maternal adiponectin, leptin, resistin and insulin levels at the end of pregnancy were compared among groups and correlated with maternal and perinatal outcomes. Data were analyzed by ANOVA and correlation tests, with a p value <0.05 being considered as significant., Results: Obese pregnant women showed higher leptin levels (p = 0.0021). Leptin levels were positively correlated with prepregnancy body mass index-BMI (r = 0.57), gestational (37 or 38 weeks of gestation) BMI (r = 0.39), hypertension (r = 0.27), and hyperglycemia (r = 0.30), and negatively associated with newborns' abdominal circumference (r = -0.25). Adiponectin concentrations were negatively correlated with gestational BMI (r = -0.29) and newborns' cephalic circumference (r = -0.27) and positively correlated with birth weight (r = 0.23). Insulin concentrations correlated positively with prepregnancy BMI (r = 0.38), gestational BMI (r = 0.24) and maternal hyperglycemia (r = 0.26)., Conclusions: Our findings support the relationship between markers of obesity and maternal-fetal outcomes. Maternal insulin and adipokines levels showed an independent relationship with mother and newborns outcomes, respectively. In this studied population, the results indirectly reinforce the importance of maternal weight control before and during pregnancy to avoid adverse outcomes to mother and their newborns.

Purpose: To evaluate the contamination index of metals and pesticides in pregnant women, and to relate this to perinatal outcomes., Methods: Descriptive, retrospective, exploratory study, developed from existing secondary data analyses at Level III maternity center. A total of 40 mothers with their newborns (NB), living in a rural area in Botucatu- Brazil and surrounding region. Blood samples from mothers and newborn were collected to determine the total contamination index for metals and pesticides. The concentrations of each metal and each pesticide were determined in blood samples of mothers and their newborns by Rudge's results. After obtaining these concentrations, the total contamination index in mother and NB was calculated, along with its correlation with clinical parameters of NB., Results: There was no correlation (p> 0.05) between maternal contamination index with NB clinical parameters, and NB contamination index versus NB clinical parameters., Conclusion: The maternal contamination index of metals and pesticides was not related to perinatal outcomes, but it could be used as baseline parameter in future toxicological studies, regarding to long-term toxic characteristics as persistent organic pollutants, its long half-lives, bioacumulative, and expected to impose serious health effects on humans.

Introduction: A number of physical and psychological changes that occur during pregnancy can stimulate the development of psychological disorders such as anxiety and depression. The study evaluated psychological aspects related to maternal depression and anxiety in pregnant women with diabetes mellitus or hyperglycemia, contrasting the results with those of non-diabetic pregnant women., Method: In a prospective and longitudinal approach, two questionnaires were applied and validated for use in Brazil, the Beck depression inventory and the State-Trait Anxiety Inventory. The questionnaires were applied to pregnant women at the first prenatal visit or at the time of disease diagnosis (T1) and reapplied at admission for delivery (T2). Regardless of the degree of hyperglycemia, both at first and in the second stage most women had severe anxiety trait. In early pregnancy (T1), however, severe state anxiety was more frequent in women with hyperglycemia than in those from the NG group., Results: Most pregnant women showed moderate state anxiety over their pregnancy, regardless of glycemic status. In early pregnancy, however, severe state anxiety was more prevalent in hyperglycemic women than in those with normal glycemic status. Most women showed moderate trait anxiety and mild depression in both early and late pregnancy, irrespective of glycemic status., Conclusion: The incidence of severe state anxiety in early pregnancy is more frequent in women with diabetes or hyperglycemia, but their levels of trait anxiety and depression are not affected by glycemic status.

Background: Metabolic syndrome (MetS) is a cluster of risk factors for type 2 diabetes (Type2 DM) and cardiovascular diseases (CVD), and its prevalence varies based on region, population, and sex. Newborns of women with MetS have a greater risk of adverse perinatal outcomes. This study explores the prevalence of metabolic syndrome in non-diabetic, pregnant Angolan women and the adverse perinatal outcomes associated with it., Methods: This cross-sectional study collected the demographic, anthropometric and clinical data of 675 pregnant women in the maternity ward of General Hospital in Huambo, Angola. Metabolic syndrome was defined using four criteria: the third report of the National Cholesterol Education Program Adult Treatment Panel (ATPIII), the Joint Interim Statement (JIS), and definitions by both Bartha et al. and Chatzi et al., Results: The crude prevalence of metabolic syndrome was 36.6 % based on the JIS definition, 29.2 % based on NCEP ATPIII, 12.6 % based on Chatzi et al. and 1.8 % based on Bartha et al. In general, the prevalence of adverse perinatal outcomes was 14.1 %., Conclusions: There was a high prevalence of metabolic syndrome, depending on the criteria used, and thus a great need to harmonize the criteria and cutoff points. Perinatal adverse outcomes were higher in pregnant women with metabolic syndrome.

Objective: This study aimed at correlating maternal blood glucose levels with DNA damage levels in the offspring of women with diabetes or mild gestational hyperglycemia (MGH)., Methodology: Based on oral glucose tolerance test results and glycemic profiles, 56 pregnant women were allocated into 3 groups: nondiabetes, MGH, and diabetes. The offspring of these women (56 infants) were also evaluated. Maternal peripheral blood and umbilical cord blood samples were collected and processed for biochemical and DNA damage analysis by the comet assay., Results: A positive correlation between maternal blood glucose mean and increased offspring DNA damage levels was observed. Hyperglycemia played a role in offspring DNA damage, but other diabetes-induced complications were also involved., Conclusion: Increased maternal blood glucose levels can lead to increased offspring DNA damage levels. Therefore, the monitoring, control, and treatment of pregnant women with diabetes and MGH are highly important to ensure a risk-free pregnancy and healthy infants., (© The Author(s) 2015.)

Objective: Investigate the DNA damage and its cellular response in blood samples from both mother and the umbilical cord of pregnancies complicated by hyperglycemia., Methods: A total of 144 subjects were divided into 4 groups: normoglycemia (ND; 46 cases), mild gestational hyperglycemia (MGH; 30 cases), gestational diabetes mellitus (GDM; 45 cases) and type-2 diabetes mellitus (DM2; 23 cases). Peripheral blood mononuclear cell (PBMC) isolation and/or leukocytes from whole maternal and umbilical cord blood were obtained from all groups at delivery. Nuclear and mitochondrial DNA damage were measured by gene-specific quantitative PCR, and the expression of mRNA and proteins involved in the base excision repair (BER) pathway were assessed by real-time qPCR and Western blot, respectively. Apoptosis was measured in vitro experiments by caspase 3/7 activity and ATP levels., Results: GDM and DM2 groups were characterized by an increase in oxidative stress biomarkers, an increase in nuclear and mitochondrial DNA damage, and decreased expression of mRNA (APE1, POLβ and FEN1) and proteins (hOGG1, APE1) involved in BER. The levels of hyperglycemia were associated with the in vitro apoptosis pathway. Blood levels of DNA damage in umbilical cord were similar among the groups. Newborns of diabetic mothers had increased expression of BER mRNA (APE1, POLβ and FEN1) and proteins (hOGG1, APE1, POLβ and FEN1). A diabetes-like environment was unable to induce apoptosis in the umbilical cord blood cells., Conclusions: Our data show relevant asymmetry between maternal and fetal blood cell susceptibility to DNA damage and apoptosis induction. Maternal cells seem to be more predisposed to changes in an adverse glucose environment. This may be due to differential ability in upregulating multiple genes involved in the activation of DNA repair response, especially the BER mechanism. However if this study shows a more effective adaptive response by the fetal organism, it also calls for further studies to determine the limit of this response that definitely changes the fate of a fetus under these conditions of cellular stress.

The present study characterized natural killer cells and cytokines in diabetic mothers, their placenta, and fetus. In the maternal blood from the hyperglycemic groups, the CD16(+)CD56(-) NK cells increased, whereas that of CD16(+)CD56(+) decreased in gestational diabetes mellitus [GDM] group. Cord blood from type 2 diabetes [DM-2] showed a higher proportion of CD16(+)CD56(-) and CD16(-)CD56(+). The placental extravillous layer of GDM and DM-2 showed an increase of CD16(+)CD56(-) cells and, irrespective of region, the proportion of CD16(-)CD56(+) cells was higher in mild gestational hyperglycemia [MGH] and GDM and lower in DM-2. IL-2 was lower in maternal blood and IFN-γ higher in maternal and cord blood from the GDM group. IL-17 was higher in maternal and cord blood from the DM-2 group. The placental extravillous layer of the MGH showed high levels of IL-4, IL-6, IL-10, IL-17, and IFN-γ and low levels of IL-1β and IL-8, whereas the placental villous layer contained high levels of IL-17 and IFN-γ. The GDM group, irrespective of region, showed higher levels of IL-8. The DM-2 group, irrespective of region, placenta showed high levels of TNF-α, IL-17, and IFN-γ. The hyperglycemia produces an inflammatory environment with a high content of inflammatory cytokines and cells expressing CD16(+).

Context and Objective: Bacterial vaginosis occurs frequently in pregnancy and increases susceptibility to sexually transmitted infections (STI). Considering that adolescents are disproportionally affected by STI, the aim of this study was to evaluate the cervicovaginal levels of interleukin (IL)-1 beta, IL-6, IL-8 and bacterial sialidase in pregnant adolescents with bacterial vaginosis., Design and Setting: Cross-sectional study at mother and child referral units in Belém, Pará, Brazil., Methods: Vaginal samples from 168 pregnant adolescents enrolled were tested for trichomoniasis and candidiasis. Their vaginal microbiota was classified according to the Nugent criteria (1991) as normal, intermediate or bacterial vaginosis. Cervical infection due to Chlamydia trachomatisand Neisseria gonorrhoeae was also assessed. Cytokine and sialidase levels were measured, respectively, using enzyme-linked immunosorbent assays and MUAN conversion in cervicovaginal lavages. Forty-eight adolescents (28.6%) were excluded because they tested positive for some of the infections investigated. The remaining 120 adolescents were grouped according to vaginal flora type: normal (n = 68) or bacterial vaginosis (n = 52). Their cytokine and sialidase levels were compared between the groups using the Mann-Whitney test (P < 0.05)., Results: The pregnant adolescents with bacterial vaginosis had higher levels of IL-1 beta, IL-6 and IL-8 (P < 0.05). Sialidase was solely detected in 35 adolescents (67.2%) with bacterial vaginosis., Conclusions: Not only IL-1 beta and sialidase levels, but also IL-6 and IL-8 levels are higher in pregnant adolescents with bacterial vaginosis, thus indicating that this condition elicits a more pronounced inflammatory response in this population, which potentially increases vulnerability to STI acquisition.

Purpose: To analyze the physiological and biochemical measurements before, during and after pregnancy of healthy rats., Methods: Wistar adult females rats (n=8) were weighed and blood samples were obtained before, during and after pregnancy for biochemical determinations, chow intake, water consumption and milk production were evaluated. At day 10 postpartum, the rats were killed for weighing of organs and adipose tissues., Results: The results showed increase in body weight, serum insulin and ingestion of water and chow. At day 17 pregnancy, presented normal values in the OGTT. At days 7, 14 and 20 of pregnancy, there was increase in triglyceride levels. At term pregnancy, there was weight gain due to fetal growth. In the postpartum period presented reduced blood glucose levels. The glycemic means were reduced during and after pregnancy compared to after pregnancy. The triglyceride concentrations were increased before and during pregnancy in relation to after pregnancy. The total cholesterol levels presented no changes., Conclusion: The use of experimental animals is suitable for evaluation of metabolic changes because the profile of answers found in this study was similar to human profile, showing the relevance of translational research to better understand the pathophysiological mechanisms and possible treatment for diseases.

To evaluate the effect of swimming in pregnant rats born with intrauterine growth restriction (IUGR) and their offspring, IUGR rats were obtained using the streptozotocin-induced severe diabetic (SD) rats. In this study, the nondiabetic parental generation presented 10 rats and diabetic parental generation presented 116 rats. Of these, the mated nondiabetic female rats were 10 and the number of diabetic rats was 45. In relation to term pregnancy, there were 10 animals in the nondiabetic group and 15 rats in the diabetic group. In the offspring of SD rats (IUGR group), 43 females were classified as small for pregnancy age, 19 rats were classified as appropriate for pregnancy age, and 0 female was classified as large for pregnancy age. The nondiabetic and SD pregnant rats generated offspring with appropriate (control [C]) and small (IUGR) weight for pregnancy age, respectively. At adult life, the C group was maintained as nonexercised C group and IUGR rats were distributed into 2 subgroups, namely, nonexercised (IUGR) and exercised (IUGRex). The rate of mated rats in the IUGR group was reduced compared to the C group. During pregnancy, the IUGR rats presented hyperinsulinemia, impaired reproductive outcomes, decreased body weight, hypertriglyceridemia, and hyperlactacidemia. The IUGRex presented reduced insulin and triglyceride levels. Thus, swimming improved lipid metabolism and increased insulin sensitivity. However, the offspring showed retarded growth, reinforcing the need to stimulate the exercise practice in women under supervision with different professional expertise to promote appropriate gestational conditions and improve perinatal outcomes., (© The Author(s) 2015.)

The potential benefits and risks of physical exercise on fetal development during pregnancy remain unclear. The aim was to analyze maternal oxidative stress status and the placental morphometry to relate to intrauterine growth restriction (IUGR) from diabetic female rats submitted to swimming program after embryonic implantation. Pregnant Wistar rats were distributed into 4 groups (11 animals/group): control-nondiabetic sedentary rats, control exercised-nondiabetic exercised rats, diabetic-diabetic sedentary rats, and diabetic exercised-diabetic exercised rats. A swimming program was used as an exercise model. At the end of pregnancy, the maternal oxidative stress status, placental morphology, and fetal weight were analyzed. The swimming program was not efficient to reduce the hyperglycemia-induced oxidative stress. This fact impaired placental development, resulting in altered blood flow and energy reserves, which contributed to a deficient exchange of nutrients and oxygen for the fetal development, leading to IUGR., (© The Author(s) 2014.)

Background: Pregnant women with mild gestational hyperglycemia present a high risk for hypertension and obesity, and appear to reproduce the model of metabolic syndrome in pregnancy, including hyperinsulinemia and insulin resistance. Diabetic patients have a higher frequency of the IRS-1 Gly972Arg variant and this polymorphism is directly related to insulin resistance and subsequent hyperglycemia. In diabetes, hyperglycemia and other associated factors generate reactive oxygen species that increase DNA damage. The aims of this study were to evaluate the presence of the IRS-1 Arg972 polymorphism in pregnant women with diabetes or mild gestational hyperglycemia, and in their newborns. Additionally, we evaluated the level of primary DNA damage in lymphocytes of Brazilian pregnant women and the relationship between the amount of genetic damage and presence of the polymorphism., Methods: A based on the oral glucose tolerance test (OGTT) results and on glycemic profiles (GP), as follows: non-diabetic group, mild gestational hyperglycemia (MGH) and diabetic group. Eighty-five newborns were included in the study. Maternal peripheral blood samples and umbilical cord blood samples (5-10 mL) were collected for genotyping by PCR-RFLP and for comet assays., Results: The prevalence of genotype Gly/Arg in pregnant women groups was not statistically significant. In newborns, the frequency of Gly/Arg was significantly higher in the MGH and diabetic groups than in the non-diabetic group. Taken together, groups IIA and IIB (IIA + IIB; diabetes) presented lower amounts of DNA damage than the non-diabetic group (p = 0.064). No significant association was detected between genetic damage and the presence of the Arg972 genotype in pregnant women., Conclusion: The polymorphism was more prevalent in newborns of diabetic and MGH women. We believe that it is necessary to increase the number of subjects to be examined in order to better determine the biological role of the Arg972 polymorphism in these patients. Despite being classified as low-risk, pregnant women with mild gestational hyperglycemia characterize a population of maternal and perinatal adverse outcomes, and that, together with their newborns, require better monitoring by professionals and health services.

Aims: TNF-α is a diabetogenic cytokine associated with adverse outcomes during pregnancy that can be counterbalanced by IL-10. We have investigated IL-10 and TNF-α balance at maternal and placental levels in hyperglycemia-associated pregnancies., Methods: One hundred and ninety-two pregnant women participated, which included normoglycemic women (ND) and women with mild gestational hyperglycemia (MGH), gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (DM2). Maternal plasma and placental tissue IL-10 and TNF-α levels were measured by ELISA and placental TNF-α was also immunolocalized., Results: Maternal plasma TNF-α levels were highest in GDM (p=0.0190), whereas TNF-α levels were highest in placental tissues in DM2 (p=0.0095). Immunohistochemistry also showed strong reactivity with anti-TNF-α antibody in the villous structures in the DM2 group. Conversely, IL-10 levels were lowest in maternal plasma of the DM2 group (p=0.0228). The TNF-α/IL-10 ratio in maternal plasma progressively increased with the severity of hyperglycemia (p<0.0001), being highest in placenta of the DM2 group (p=0.0150). In both, plasma and placenta, TNF-α/IL-10 ratio were correlated with mean maternal glycemia and HbA1c levels., Conclusions: Alterations of placenta and serum TNF-α/IL-10 balance with predominance of TNF-α were correlated with the severity of hyperglycemia during gestation. This association may offer insight into the pathogenesis of gestational hyperglycemia and associated pregnancy outcomes., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

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.

This study aimed at evaluating the effect of swimming before and during pregnancy on rats born with intrauterine growth restriction (IUGR) and their offspring. For this, nondiabetic and streptozotocin-induced severely diabetic (SD) pregnant rats were mated and generated offspring with appropriate (control, C) and small (IUGR) for pregnancy age, respectively. Following that, C and IUGR groups were further distributed into nonexercised control (C), exercised control (Cex), nonexercised IUGR (IUGR), and exercised IUGR (IUGRex). IUGR rats presented lower mating rate than control rats. Regardless of physical exercise IUGR rats presented decreased body weight from birth to lactation. At 90 days of life, IUGR rats presented glucose intolerance. Maternal organ weights were increased and relative adiposity of IUGRex rats was lower than Cex. IUGR and IUGRex offspring presented reduced body weight than C and Cex, respectively. IUGRex dams presented an increased rate of appropriate for pregnancy age newborns. IUGEex male and female offspring relative brain weight was increased compared with Cex. Therefore, swimming before and during pregnancy prevented glucose intolerance, reduced general adiposity, and increased maternal and offspring organ weight in rats, showing the benefit of physical exercise for IUGR rats.

Background: Diabetic pregnancy have increased rates of congenital malformation and neonatal mortality. In vitro studies suggest hyperglycemia associated with diabetes impair embryogenesis but in vivo investigations on maternal hyperglycemic insult and early embryo development are scarce. We evaluated the embryofetal development on experimental diabetes models to assess whether hyperglycemia at preimplantation period impairs the progression of pregnancy., Methods: Different hyperglycemic intensities were obtained by two experimental diabetes models. Female Sprague Dawley rats received streptozotocin at birth (mild diabetes) or at day 90 of life (severe diabetes). For both diabetic groups hyperglycemia was confirmed 5 days after diabetes induction and the mating was performed around 100 day of life. For preimplantation analysis, embryos were recovered at D4 of pregnancy. Another group of animals was submitted to laparotomy at D21 to assess contents of the uterus and fetal viability., Results: Mild (i) and Severe (ii) diabetes modified the early development. Degenerating embryos percentage was higher compared to control (11%) (i) 30.7%, (ii) 37.3%. Cell number mean dropped according to hyperglycemic intensity (control 30.57, (i) 21.42, (ii) 13.42). Pre and post-implantation loss rates were higher in diabetic groups. The fetal viability also decreased from 96% in the control group to (i) 78.7% and (ii) 80.6%., Conclusion: Our results show that during diabetic pregnancy, preimplantation embryos present decreased cell number due to higher apoptosis rates, which are dependent of the hyperglycemic intensity. Moreover, fetal viability was also decreased suggesting that the quality of these embryos at long-term may be questioned., (Copyright © 2014 John Wiley & Sons, Ltd.)

The aim of the present study was at evaluating the effects of oxidative stress in blood and placenta of mild diabetic Wistar rats. At birth, Wistar rats received citrate buffer (nondiabetic group, n = 15) and another group received streptozotocin (100 mg/kg, subcutaneous) to induce mild diabetes (diabetic, n = 15). The glycemia of these pregnant adult female rats were evaluated at days 0, 7, 14, and 21 of pregnancy, and at term pregnancy, the blood and placental samples were collected for oxidative stress measurements. The mild diabetes caused glycemia superior to 120 mg/dL during pregnancy, increased superoxide dismutase, glutathione peroxidase, glutathione reductase activities, and malondialdehyde levels in the blood, and catalase activity in the placenta. Thus, mild diabetes increased activities of antioxidant substances aiming at defending against the exacerbated oxidative stress but were not enough. The placenta also answered to diabetic milieu and increased antioxidant defense, showing that even a mild hyperglycemia was enough to cause placental and maternal blood changes., (© The Author(s) 2014.)

The prevalence of urinary incontinence in diabetic pregnant women is significantly high two years after cesarean section. Incontinence can be the most common consequence of hyperglycemia compared to other complications. Thus, identifying the risk factors for the development of urinary incontinence in diabetes is the major aim in the prevention of this very common condition. Recent surveys have shown that not only muscle but also the urethral extracellular matrix play an important role in the mechanism of urinary continence. Translational work on rats by our research group showed that diabetes during pregnancy damages the extracellular matrix and urethral striated muscle, a fact that may explain the high prevalence of urinary incontinence and pelvic floor dysfunction in women with gestational diabetes mellitus. Diabetes affects the expression, organization and change in extracellular matrix components in different organs, and tissue remodeling and fibrosis appear to be a direct consequence of it. Therefore, understanding the impact of modifiable risk factors, such as diabetes, which involves using preventive strategies, can reduce the rates of urinary incontinence and the health care costs, and improve the quality of life of women, especially during pregnancy and postpartum.

Background: To evaluate waist circumference (WC) measured at 20-24 weeks of gestation as a predictor of gestational diabetes mellitus (GDM)., Methods: This cross-sectional study included 240 women at 20-24 weeks of gestation. At enrollment, WC was measured, and both prepregnancy and gestational body mass index (BMI) were estimated. According to the results of 75-g oral glucose tolerance test (OGTT) performed at 24-28 weeks, subjects were allocated into two groups, non-GDM and GDM. WC sensitivity and specificity, and odds ratios (OR) and 95% confidence intervals for BMI and WC were estimated, and a receiver operating characteristics curve was generated., Results: Of the 240 pregnant women enrolled, 31 (13%) had GDM. Prepregnancy BMI (OR = 4.21), gestational BMI (OR = 3.17) and WC at 20-24 weeks (OR = 4.02) correlated with GDM risk. At 20-24 weeks, a WC of 85.5-88.5 cm was the optimal cutoff point for predicting GDM (Sens/Spec balance between 87.1/41.1% and 77.4/56.9%)., Conclusion: At 20-24 weeks of gestation, WC values in the range of 86-88 cm showed to be a good performance in predicting GDM.

Introduction and Hypothesis: Diabetes mellitus (DM) during pregnancy is associated with high levels of urinary incontinence (UI) and pelvic floor muscle dysfunction. Mild DM can lead to changes in urethral striated muscle and extracellular matrix (ECM) in pregnant rats considering both structures as an entire system responsible for urinary continence., Methods: Ninety-two female Wistar rats were distributed in four experimental groups: virgin, pregnant, diabetic, and diabetic pregnant. In adult life, parental nondiabetic female rats were mated with nondiabetic male rats to obtain newborns. At the first day of birth, newborns received citrate buffer (nondiabetic group) or streptozotocin 100 mg/kg body weight, subcutaneous route (mild DM group). At day 21 of the pregnancy, the rats were lethally anesthetized and the urethra and vagina were extracted as a unit. Urethral and vaginal sections were cut and analyzed by: (a) cytochemical staining for ECM and muscle structural components, (b) immunohistochemistry to identify fast- and slow-muscle fibers, and (c) transmission electron microscopy for ultrastructural analysis of urethral striated muscle., Results: In comparison with the three control groups, variations in the urethral striated muscle and ECM from diabetic pregnant rats were observed including thinning, atrophy, fibrosis, increased area of blood vessels, mitochondria accumulation, increased lipid droplets, glycogen granules associated with colocalization of fast and slow fibers, and a steady decrease in the proportion of fast to slow fibers., Conclusions: Mild DM and pregnancy can lead to a time-dependent disorder and tissue remodeling in which the urethral striated muscle and ECM has a fundamental function.

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.

Glucose homeostasis is controlled by endocrine pancreatic cells, and any pancreatic disturbance can result in diabetes. Because 8% to 12% of diabetic pregnant women present with malformed fetuses, there is great interest in understanding the etiology, pathophysiological mechanisms, and treatment of gestational diabetes. Hyperglycemia enhances the production of reactive oxygen species, leading to oxidative stress, which is involved in diabetic teratogenesis. It has also been suggested that maternal diabetes alters embryonic gene expression, which might cause malformations. Due to ethical issues involving human studies that sometimes have invasive aspects and the multiplicity of uncontrolled variables that can alter the uterine environment during clinical studies, it is necessary to use animal models to better understand diabetic pathophysiology. This review aimed to gather information about pathophysiological mechanisms and fetal outcomes in streptozotocin-induced diabetic rats. To understand the pathophysiological mechanisms and factors involved in diabetes, the use of pancreatic regeneration studies is increasing in an attempt to understand the behavior of pancreatic beta cells. In addition, these studies suggest a new preventive concept as a treatment basis for diabetes, introducing therapeutic efforts to minimize or prevent diabetes-induced oxidative stress, DNA damage, and teratogenesis.

The increased production of reactive oxygen species (ROS) plays a key role in pathogenesis of diabetic complications. ROS are generated by exogenous and endogenous factors such as during hyperglycemia. When ROS production exceeds the detoxification and scavenging capacity of the cell, oxidative stress ensues. Oxidative stress induces DNA damage and when DNA damage exceeds the cellular capacity to repair it, the accumulation of errors can overwhelm the cell resulting in cell death or fixation of genome mutations that can be transmitted to future cell generations. These mutations can lead to and/or play a role in cancer development. This review aims at (i) understanding the types and consequences of DNA damage during hyperglycemic pregnancy; (ii) identifying the biological role of DNA repair during pregnancy, and (iii) proposing clinical interventions to maintain genome integrity. While hyperglycemia can damage the maternal genetic material, the impact of hyperglycemia on fetal cells is still unclear. DNA repair mechanisms may be important to prevent the deleterious effects of hyperglycemia both in mother and in fetus DNA and, as such, prevent the development of diseases in adulthood. Hence, in clinical practice, maternal glycemic control may represent an important point of intervention to prevent the deleterious effects of maternal hyperglycemia to DNA.

Ethnopharmacological Relevance: Azadirachta indica A. Juss, popularly known as neem, presents medicinal and insecticide properties. However, the repercussions of the neem maternal treatment on fetal development should be investigated. Thus, the aim of this study was to evaluated the effects of Azadirachta indica (neem) on the frequency of congenital malformations in fetuses from rats., Materials and Methods: Pregnant rats were randomly distributed into three experimental groups: NT=non-treated; TOil=treated with neem seed oil (1.2 mL/day); TAP=treated with active principle of Azadirachta indica (azadirachtin-1.0 mg/mL/day). The neem oil (1.2 mL/day) or azadirachtin (1.0 mg/mL/day) treatments were orally administered throughout pregnancy. Blood samples were collected on days 0, 7, 14 and 20 of pregnancy. Oral glucose test tolerance (OGTT) was performed at day 17 of pregnancy for estimation of total area under the curve (AUC). At term, the fetuses were collected and external and internal (visceral and skeletal) malformations were analyzed., Results: The data showed that the dams treated with neem seed oil and Azadirachtin had no significant change in glucose levels and AUC. It was also verified that neem oil treatment contributed to increase the frequency of malformation/variation, in particular the visceral in their fetuses, while neither significant result was observed in TAP group., Conclusion: In conclusion, neem seed oil treatment administered during pregnancy caused abnormalities in rat fetuses, showing teratogenic effect but the Azadirachtin (active principle) presented no impairment in the fetuses., (© 2013 Elsevier Ireland Ltd. All rights reserved.)

Preeclampsia (PE), a specific syndrome of pregnancy, can be classified into early and late onset, depending on whether clinical manifestations occur before or after 34 weeks' gestation. We determined whether plasma concentrations of Hsp60 and Hsp70 were related to circulating cytokine levels, as well as kidney and liver functions, in early- and late-onset PE. Two hundred and thirty-seven preeclamptic women (95 with early- and 142 with late-onset PE) were evaluated. Plasma levels of Hsp60, Hsp70, and their specific antibodies, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1, IL-10, IL-12, and soluble TNF-α-receptor I (sTNFRI) concentrations, were determined by enzyme-linked immunosorbent assay (ELISA). Concentrations of Hsp70, TNF-α, IL-1β, IL-12, and sTNFRI were significantly elevated in patients with early-onset PE compared with women with late-onset PE; IL-10 levels were significantly lower in the early-onset PE group. Concentrations of urea, uric acid, proteinuria, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and lactate dehydrogenase (LDH) were also significantly higher in early-onset PE. The percentage of infants with intrauterine growth restriction was also significantly higher in women with early-onset PE. There were positive correlations between Hsp70 levels and TNF-α, TNFRI, IL-1β, IL-12, GOT, GPT, LDH, and uric acid concentrations in early-onset PE group. Thus, early-onset PE was associated with greater maternal and fetal impairment. There are differences in pathophysiology between early- and late-onset PE, highlighting by the difference in Hsp70 levels., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To evaluate the methodological and statistical design evolution of the publications in the Brazilian Journal of Gynecology and Obstetrics (RBGO) from resolution 196/96., Methods: A review of 133 articles published in 1999 (65) and 2009 (68) was performed by two independent reviewers with training in clinical epidemiology and methodology of scientific research. We included all original clinical articles, case and series reports and excluded editorials, letters to the editor, systematic reviews, experimental studies, opinion articles, besides abstracts of theses and dissertations. Characteristics related to the methodological quality of the studies were analyzed in each article using a checklist that evaluated two criteria: methodological aspects and statistical procedures. We used descriptive statistics and the χ2 test for comparison of the two years., Results: There was a difference between 1999 and 2009 regarding the study and statistical design, with more accuracy in the procedures and the use of more robust tests between 1999 and 2009., Conclusions: In RBGO, we observed an evolution in the methods of published articles and a more in-depth use of the statistical analyses, with more sophisticated tests such as regression and multilevel analyses, which are essential techniques for the knowledge and planning of health interventions, leading to fewer interpretation errors.

Maternal diabetes constitutes an unfavorable environment for fetal-placental and embryonic development. It is has important repercussion in modern obstetrics, since it is associated to an increased risk of neonatal and maternal morbidity, and it still is a significant medical challenge. The increased occurrence of diabetes worldwide, the increase in diabetes type 2 in women at reproductive age and the crossed generation of intrauterine programming for diabetes type 2 are the bases for the growing interest in utilization of diabetic experimental samples, with the aim to acquire knowledge about the mechanisms that induce development alterations in gestational diabetes. Several studies have shown the benefits of diabetes prevention, with interventions in lifestyle, metabolic improvement and control of cardiovascular risk factors to substantially prevent the complications of this devastating disease. Despite these findings, the recent revolution in the scientific knowledge, and the infinite number of new therapies for diabetes, there is still a large gap between what was learned through research and what is really done in public, clinical and community health. The negative economic impact of this complacency in people, families, and national economies is alarming. It is expected that translational research in the binomial diabetes and pregnancy are implemented in centers of excellence, in both basic and applied research, and complemented by multicenter clinical studies, conducted in a pragmatic way to increase the level of scientific evidence with more reliable diagnostic and propaedeutic resources.

Objective: Experimental studies have shown that exposure to cigarette smoke has negative effects on lipid metabolism and oxidative stress status. Cigarette smoke exposure in nonpregnant and pregnant rats causes significant genotoxicity (DNA damage). However, no previous studies have directly evaluated the effects of obesity or the association between obesity and cigarette smoke exposure on genotoxicity. Therefore, the aim of the present investigation was to evaluate DNA damage levels, oxidative stress status and lipid profiles in obese Wistar rats exposed to cigarette smoke., Design and Methods: Female rats subcutaneously (s.c.) received a monosodium glutamate solution or vehicle (control) during the neonatal period to induce obesity. The rats were randomly distributed into three experimental groups: control, obese exposed to filtered air, and obese exposed to tobacco cigarette smoke. After a 2-month exposure period, the rats were anesthetized and killed to obtain blood samples for genotoxicity, lipid profile, and oxidative stress status analyses., Results: The obese rats exposed to tobacco cigarette smoke presented higher DNA damage, triglycerides, total cholesterol, free fatty acids, VLDL-c, HDL-c, and LDL-c levels compared to control and obese rats exposed to filtered air. Both obese groups showed reduced SOD activity. These results showed that cigarette smoke enhanced the effects of obesity., Conclusion: In conclusion, the association between obesity and cigarette smoke exposure exacerbated the genotoxicity, negatively impacted the biochemical profile and antioxidant defenses and caused early glucose intolerance. Thus, the changes caused by cigarette smoke exposure can trigger the earlier onset of metabolic disorders associated with obesity, such as diabetes and metabolic syndrome., (Copyright © 2012 The Obesity Society.)

Objective: The purpose of this study was to identify the clinical factors associated with time to hCG remission among women with low-risk postmolar GTN., Methods: This study included a non-concurrent cohort of 328 patients diagnosed with low-risk postmolar GTN according to FIGO 2002 criteria. Associations of time to hCG remission with history of prior mole, molar histology, time to persistence, use of D&C at persistence, presence of metastatic disease, FIGO score, hCG values at persistence, type of first line therapy and use of multiagent chemotherapy were investigated with both univariate and multivariate analyses., Results: Overall median time to remission was 46 days. Ten percent of the patients required multi-agent chemotherapy to achieve hCG remission. Multivariate analysis incorporating the variables significant on univariate analysis confirmed that complete molar histology (HR 1.45), metastatic disease (HR 1.66), use of multi-agent therapy (HR 2.00) and FIGO score (HR 1.82) were associated with longer time to remission. There was a linear relationship between FIGO score and time to hCG remission. Each 1-point increment in FIGO score was associated with an average 17-day increase in hCG remission time (95% CI: 12.5-21.6)., Conclusions: Complete mole histology prior to GTN, presence of metastatic disease, use of multi-agent therapy and higher FIGO score were independent factors associated with longer time to hCG remission in low-risk GTN. Identifying the prognostic factors associated with time to remission and effective counseling may help improve treatment planning and reduce anxiety in patients and their families., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the effects of exercise prior to or during pregnancy on maternal reproductive outcome, biochemical profile, and on fetal anomaly frequency in a rat pregnancy model utilizing chemically induced diabetes. Wistar rats (minimum n = 11 animals/group) were randomly assigned the following groups: group 1 (G1), sedentary, nondiabetic; G2, nondiabetic, exercised during pregnancy; G3, nondiabetic, exercised prior to and during pregnancy; G4, sedentary, diabetic; G5, diabetic, exercised during pregnancy; and G6, diabetic, exercised prior to and during pregnancy. A swimming program was utilized for moderate exercise. On day 21 of pregnancy, all rats were anesthetized to obtain blood for biochemical measurements. The gravid uterus was weighed with its contents, and the fetuses were analyzed. The nondiabetic rats exercised prior to pregnancy presented a reduced maternal weight gain. Besides, G2 and G3 groups showed decreased fetal weights at term pregnancy, indicating slight intrauterine growth restriction (IUGR). In the diabetic dams, the swimming program did not have antihyperglycemic effects. The exercise applied only during pregnancy caused severe IUGR, as confirmed by reduced fetal weight mean, fetal weight classification, and ossification sites. Nevertheless, exercise was not a teratogenic factor and improved the rats' lipid profiles, demonstrating that the exercise presented possible benefits, but there are also risks prior and during pregnancy, especially in diabetic pregnant women.

Obese Black women are at increased risk for development of gestational diabetes mellitus and have worse perinatal outcomes than do obese women of other ethnicities. Since hsp72 has been associated with the regulation of obesity-induced insulin resistance, we evaluated associations between glucose ingestion, hsp72 release and insulin production in Black pregnant women. Specifically, the effect of a 50-g glucose challenge test (GCT) on heat shock protein and insulin levels in the circulation 1 h later was evaluated. Hsp27 and hsp60 levels remained unchanged. In contrast, serum levels of hsp72 markedly increased after glucose ingestion (p = 0.0054). Further analysis revealed that this increase was limited to women who were not obese (body mass index <30). Insulin levels pre-GCT were positively correlated with body mass index (p = 0.0189). Median insulin concentrations also increased post GCT in non-obese women but remained almost unchanged in obese women. Post-GCT serum hsp72 concentrations were inversely correlated with post GCT insulin concentrations (p = 0.0111). These observations suggest that glucose intake during gestation in Black women rapidly leads to an elevation in circulating hsp72 only in non-obese Black women. The release of hsp72 may regulate the extent of insulin production in response to a glucose challenge and, thereby, protect the mother and/or fetus from development of hyperglycemia, hyperinsulinemia, and/or immune system alterations.

Immune response changes induced by diabetes are a risk factor for infections during pregnancy and may modify the development of the newborn's immune system. The present study analyzed colostrum and maternal and cord blood of diabetic women to determine (1) the levels of the cytokines IFN- γ and TGF- β and (2) phagocytic activity after incubation with cytokines. Methods. Colostrum and maternal and cord blood samples were classified into normoglycemic (N = 20) and diabetic (N = 19) groups. Cytokine levels, superoxide release, rate of phagocytosis, bactericidal activity, and intracellular Ca(2+) release by phagocytes were analyzed in the samples. Irrespective of glycemic status, IFN- γ and TGF- β levels were not changed in colostrum and maternal and cord blood. In maternal blood and colostrum, superoxide release by cytokine-stimulated phagocytes was similar between the groups. Compared to spontaneous release, superoxide release was stimulated by IFN- γ and TGF- β in normoglycemic and diabetic groups. In the diabetic group, cord blood phagocytes incubated with IFN- γ exhibited higher phagocytic activity in response to EPEC, and maternal blood exhibited lower microbicidal activity. These data suggest that diabetes interferes in maternal immunological parameters and that IFN- γ and TGF- β modulate the functional activity of phagocytes in the colostrum, maternal blood, and cord blood of pregnant diabetic women.

Context and Objective: Pregnancies complicated by diabetes are associated with increased neonatal and maternal complications. The most serious maternal complication is the risk of developing type 2 diabetes, 10-12 years after the delivery. For rigorous control over blood glucose, pregnant women are treated through ambulatory management or hospitalization. The aim of this study was to evaluate the effectiveness of ambulatory management versus hospitalization in pregnancies complicated by diabetes or hyperglycemia., Design and Setting: Systematic review conducted in a public university hospital., Methods: A systematic review of the literature was performed and the main electronic databases were searched. The date of the most recent search was September 4, 2011. Two authors independently selected relevant clinical trials, assessed their methodological quality and extracted data., Results: Only three studies were selected, with small sample sizes. There was no statistically significance different between ambulatory management and hospitalization, regarding mortality in any of the subcategories analyzed: perinatal and neonatal deaths (relative risk [RR] 0.65; 95% confidential interval [CI]: 0.11 to 3.84; P = 0.63); neonatal deaths (RR 0.29; 95% CI: 0.01 to 6.07; P = 0.43); and infant deaths (RR 0.29; 95% CI: 0.01 to 6.07; P = 0.43)., Conclusions: This review, based on studies with high or moderate risk of bias, showed that there was no statistically significant difference between ambulatory management and hospital care, regarding reduction of mortality rates in pregnancies complicated by diabetes or hyperglycemia. It also suggested that there is a need for further randomized controlled trials on this issue.

Context and Objective: There is uncertainty in the literature regarding the theory that obstetric events and pelvic floor injuries give rise to lower risk of subsequent urinary incontinence among women delivering via cesarean section than among women delivering vaginally. The objective of this study was to assess the two-year postpartum prevalence of urinary incontinence and pelvic floor muscle dysfunction and the factors responsible for them., Design and Setting: Cross-sectional study, conducted in a public university., Methods: 220 women who had undergone elective cesarean section or vaginal childbirth two years earlier were selected. Their urinary incontinence symptoms were investigated, and their pelvic floor muscle dysfunction was assessed using digital palpation and a perineometer., Results: The two-year urinary incontinence prevalences following vaginal childbirth and cesarean section were 17% and 18.9%, respectively. The only risk factor for pelvic floor muscle dysfunction was weight gain during pregnancy. Body mass index less than 25 kg/m 2 and normal pelvic floor muscle function protected against urinary incontinence. Gestational urinary incontinence increased the risk of two-year postpartum urinary incontinence., Conclusion: Gestational urinary incontinence was a crucial precursor of postpartum urinary incontinence. Weight gain during pregnancy increased the subsequent risk of pelvic floor muscle dysfunction, and elective cesarean section did not prevent urinary incontinence.

We evaluated associations between the concentrations of heat shock proteins (hsp60 and hsp70) and their respective antibodies, alterations in maternal reproductive performance, and fetal malformations in pregnant rats with hyperglycemia. Mild diabetes (MD) or severe diabetes (SD) was induced in Sprague-Dawley rats prior to mating; non-treated non-diabetic rats (ND) served as controls. On day 21 of pregnancy, maternal blood was analyzed for hsp60 and hsp70 and their antibodies; and fetuses were weighed and analyzed for congenital malformations. Hsp and anti-hsp levels were correlated with blood glucose levels during gestation. There was a positive correlation between hsp60 and hsp70 levels and the total number of malformations (R = 0.5908, P = 0.0024; R = 0.4877, P = 0.0134, respectively) and the number of malformations per fetus (R = 0.6103, P = 0.0015; R = 0.4875, P = 0.0134, respectively). The anti-hsp60 IgG concentration was correlated with the number of malformations per fetus (R = 0.3887, P = 0.0451) and the anti-hsp70 IgG level correlated with the total number of malformations (R = 0.3999, P = 0.0387). Moreover, both hsp and anti-hsp antibodies showed negative correlations with fetal weight. The results suggest that there is a relationship between hsp60 and hsp70 levels and their respective antibodies and alterations in maternal reproductive performance and impaired fetal development and growth in pregnancies associated with diabetes.

The presence of diabetes in pregnancy leads to hormonal and metabolic changes making inappropriate intrauterine environment, favoring the onset of maternal and fetal complications. Human studies that explore mechanisms responsible for changes caused by diabetes are limited not only for ethical reasons but also by the many uncontrollable variables. Thus, there is a need to develop appropriate experimental models. The diabetes induced in laboratory animals can be performed by different methods depending on dose, route of administration, and the strain and age of animal used. Many of these studies are carried out in neonatal period or during pregnancy, but the results presented are controversial. So this paper, addresses the review about the different models of mild diabetes induction using streptozotocin in pregnant rats and their repercussions on the maternal and fetal organisms to propose an adequate model for each approached issue.

Ethnopharmacological Relevance: The role of Azadirachta indica (neem) against Chagas disease and its antibiotic and antidiabetic action have been demonstrated in non-pregnant animals. However, the effects of neem on lipid metabolism and oxidative stress during pregnancy remain to be investigated. The objective of this study was to evaluate the effects of Azadirachta indica (neem) on maternal reproductive performance and biochemical parameters in non-diabetic and streptozotocin-induced mild diabetic rats (MD)., Materials and Methods: Pregnant rats were randomly distributed into six experimental groups: ND=non-treated non-diabetic (n=13); NDOil=non-diabetic treated with 1.2 mL/day neem seed oil (n=12); NDPA=non-diabetic treated with 1.0mg/mL/day azadirachtin (n=12); D=non-treated diabetic (n=13); DOil: diabetic treated with neem seed oil (n=12), and DPA=diabetic treated with azadirachtin, n=13. Treatment with either neem oil (1.2 mL/day) or azadirachtin (1.0mg/mL/day) was orally administered throughout pregnancy. Glucose test tolerance (GTT) was performed at day 17 of pregnancy and used as an inclusion criterion. At term pregnancy, maternal reproductive outcomes, lipid profile and oxidative stress status were assessed., Results: Treatment with neem oil and azadirachtin during pregnancy (1) had no hypoglycemic and anti-hyperglycemic effects on non-diabetic and diabetic rats, respectively; (2) affected OGTT glycemic levels in diabetic rats; (3) increased the proportion of fetuses classified as small for pregnancy age (SPA) in all groups; and (4) did not interfere with the lipid profile in non-diabetic dams. Neem oil reduced the rate of total cholesterol and NEFA in diabetic animals. Both neem oil and azadirachtin increased lipoperoxidation, characterized by increased MDA levels in non-diabetic rats., Conclusion: Both neem seed oil and azadirachtin impaired intrauterine development and altered antioxidant/oxidative status during pregnancy., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: To assess the influence of hydatidiform mole (HM) management setting (reference center versus other institutions) on gestational trophoblastic neoplasia (GTN) outcomes., Methods: This cohort study included 270 HM patients attending Botucatu Trophoblastic Diseases Center (BTDC, São Paulo State University, Brazil) between January 1990 and December 2009 (204 undergoing evacuation and entire postmolar follow-up at BTDC and 66 from other institutions [OIs]). GTN characteristics and outcomes were analyzed and compared according to HM management setting. The confounding variables assessed included age, gravidity, parity, number of abortions and HM type (complete or partial). Postmolar GTN outcomes were compared using Mann-Whitney's test, chi2 test or Fisher's exact test., Results: Postmolar GTN occurred in 34 (34/204 = 16.7%) BTDC patients and in 27 (27/66 = 40.9%) of those initially treated in other institutions. BTDC patients showed lower metastasis rate (5.8% vs. 48%, p = 0.003) and lower median FIGO (2002) score (2.00 [1.00, 3.00] vs. 4.00 [2.00, 7.00], p = 0.003]. Multiagent chemotherapy to treat postmolar GTN was required in 2 BTDC cases (5.9%) and in 8 OI cases (29.6%) (p = 0.017). Median time interval between molar evacuation and chemotherapy onset was shorter among BTDC patients (7.0 [6.0, 10.0] vs. 10.0 [7.0, 16.0], p = 0.040)., Conclusion: BTDC patients showed GTN characteristics indicative of better prognosis. This underscores the importance of GTD specialist centers.

Introduction: Preeclampsia is a human pregnancy-specific syndrome characterized by the onset of hypertension and proteinuria. These manifestations may occur before the 34th week of gestation or from this period on, being denominated early-onset or late-onset preeclampsia respectively. The etiology of both disorders seems to differ qualitatively; therefore, different strategies of prevention and treatment must be studied., Objectives: The aim of the present study is to determine whether the plasma levels of heat-shock proteins Hsp60 and Hsp70 as well as specific antibodies anti-Hsp60 and anti-Hsp70 may differentiate early-onset from late-onset preeclampsia., Methods: We evaluated 175 pregnant women with PE (55 early-onset PE and 120 late-onset PE). Plasma was obtained from peripheral blood and Hsp60, Hsp70 as well as anti-Hsp60 and anti-Hsp70 antibody levels were determined by enzyme immunoassay. Uric acid levels were also determined in the plasma of patients. For statistical analyses, the Mann-Whitney U-test and the Spearman rank order correlation were applied with significance level set at 5%., Results: Hsp70 levels obtained from early-onset PE group were significantly higher than the late-onset PE women and showed positive correlation with uric acid (r=0.4547; p=0.0028). The Hsp60 production was similar in both groups. Our results also indicate that there was no significant difference of anti-Hsp60 and anti-Hsp70 antibody levels between women with early- and late-onset PE. However,these antibody levels were high,indicating a strong relationship with the production of HSP60 and Hsp70 protein., Conclusion: Association between levels of Hsp70 and uric acid in plasma of patients with early-onset PE seems to reflect the oxidative stress in this group of patients. This study provides evidence that Hsp70 determination may be utilized to assess the differentiation between early- and late-onset PE., Financial Support: FAPESP 2010/09241-2., (Copyright © 2012. Published by Elsevier B.V.)

Aims: This study was conducted to evaluate maternal and placental concentrations of interleukin 10 (IL-10) and tumor necrosis factor-alpha (TNF-α) in pregnant women with glycemic mean (GM) < or ≥100 mg/dL, as well as correlate IL-10 and TNF-α placental concentrations with perinatal outcomes., Methods: One hundred eighty-six pregnant women were distributed in groups determined by a GM <100 mg/dL or a GM ≥100 mg/dL. The GM, HbA1c levels, maternal and placental concentrations of IL-10 and TNF-α, and the correlation of placental cytokines with perinatal outcomes were evaluated., Results: In maternal blood, the lowest concentrations of IL-10 (p = 0.0019) and TNF-α (p = 0.0185) were observed in the GM ≥100-mg/dL group. The placentas from GM ≥100 mg/dL group exhibited higher TNF-α concentrations (p = 0.0385). Placental IL-10 directly correlated with hemoglobin (r = 0.63; p = 0.02) and insulin (r = 0.78; p = 0.01) levels in the umbilical cord and with 1-min (r = 0.53; p = 0.0095) and 5-min (r = 0.69; p = 0.0003) Apgar scores. Placental TNF-α displayed a tendency to inversely correlate with fetal weight (r = -0.41; p = 0.05)., Conclusion: Compared to GM <100 mg/dL, GM ≥100 mg/dL was associated with a reduction in maternal IL-10 and TNF-α concentrations and increased placental TNF-α production. Placental IL-10 production was similar in both groups studied and directly correlated with hemoglobin and umbilical cord insulin levels, as well as with the 1- and 5-min Apgar scores.

This study aimed to evaluate the genotoxicity (DNA damage levels) in lymphocyte samples from pregnant Wistar rats with severe or mild diabetes and in whole blood samples from their newborns. Wistar female rats (1 and 90 days of age) and male rats (approximately 90 days of age) were used. The experiment consisted of 2 experimental groups (n=8 animals/group): 1) rats with severe diabetes, 2) rats with mild diabetes. For mild diabetes induction, the rats received streptozotocin (STZ) subcutaneously (100 mg/kg body weight) at day of birth, and those showing glycemia from 120 to 300 mg/dL in their adult life were included. For induction of severe diabetes, adult rats received 40 mg/kg STZ (intravenous route), and those showing glycemia > 300 mg/dL were included. At day 21 of pregnancy, the rats were anesthetized and euthanized for removal of maternal and fetal blood samples for determination of the oxidative DNA damage by applying Endo III and Fpg using the comet assay. Thus, the rats with mild diabetes and their offspring showed higher Fpg-sensitive sites, reflecting the damage resulting from hyperglycemia. The rats with severe diabetes and their offspring showed higher oxidative DNA damage detected by Fpg and Endo III-sensitive sites, showing general repercussions related to diabetes. The enzymatic treatment for DNA damage evidenced that the maternal repercussions of diabetes are associated with oxidative DNA damage of their newborn, which was not reflected using only the analysis of DNA damage free of the enzymes., (© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.)