Serotonin and Interleukin 10 Can Influence the Blood and Urine Viscosity in Gestational Diabetes Mellitus and Pregnancy-Specific Urinary Incontinence.

Serotonin and interleukin 10 (IL-10) may play a role in gestational diabetes mellitus. Hyperglycemic environment, the detrusor musculature of the bladder and pelvic floor muscles may become damaged, leading to urination problems and urine viscosity in pregnant women with gestational diabetes mellitus and pregnancy-specific urinary incontinence. Urine and blood samples were collected from pregnant women between 24 and 28 weeks of gestation. The serotonin concentration and cytokine IL-10 levels were evaluated in plasma and urine. In the total blood and urine, the viscosity was evaluated in the presence and absence of exogenous serotonin and IL-10. The plasma serotonin levels decreased, while the urine serotonin levels increased in the normoglycemic incontinent (NG-I), hyperglycemic continent (GDM-C), and hyperglycemic incontinent (GDM-I) groups. The IL-10 in the plasma decreased in the GDM-I group and was higher in the urine in the NG-I and GDM-I groups. The blood viscosity was higher, independently of urinary incontinence, in the GDM groups. The serotonin increased the blood viscosity from women with GDM-C and urine in the NG-I, GDM-C, and GDM-I groups. Blood and urine in the presence of IL-10 showed a similar viscosity in all groups studied. Also, no difference was observed in the viscosity in either the blood or urine when in the presence of serotonin and IL-10. These findings suggest that serotonin and IL-10 have the potential to reduce blood viscosity in pregnant women with gestational diabetes and specific urinary incontinence, maintaining values similar to those in normoglycemic women's blood.

Relaxin-2 during pregnancy according to glycemia, continence status, and pelvic floor muscle function.

INTRODUCTION AND HYPOTHESIS: To investigate relaxin-2 concentration comparing gestational diabetes mellitus (GDM) and non-GDM patients during pregnancy according to urinary incontinence (UI) and pelvic function status. METHODS: This is a cross-sectional study evaluating 282 pregnant women from 24 weeks of gestation. The participants were divided into two groups, non-GDM and GDM, according to American Diabetes Association's diabetes mellitus gestational threshold. In addition, according to subanalysis, both groups were subdivided according to the presence of pregnancy-specific urinary incontinence: non-GDM continent, non-GDM incontinent, GDM continent, and GDM incontinent. All participants filled in questionnaires on clinical, obstetric, and urinary continence status (International Consultation on Incontinence Questionnaire-Short Form, ICIQ-SF, and Incontinence Severity Index, ISI), followed by pelvic floor muscle evaluation by the PERFECT scheme in which strength, endurance, and speed of contractions were evaluated. RESULTS: Serum relaxin-2 concentrations were significantly lower in pregnant women with pregnancy-specific urinary incontinence in both non-GDM and GDM patients, but GDM showed the lowest concentration. In addition, the stratification of the groups according to pelvic floor muscle strength showed that pregnant patients with GDM and modified Oxford scale 0-2 had significantly lower levels than those who were non-GDM and GDM with Modified Oxford Scale 3-5. Relaxin-2 level was much lower in GDM incontinent pregnant women with MOS 0-2 compared to the other three groups. CONCLUSIONS: Lower relaxin-2 concentration was associated with the presence of pregnancy-specific urinary incontinence, but the combination of GDM, pregnancy-specific urinary incontinence, and lower levels of pelvic floor strength led to lower levels of relaxin-2 compared to the other three groups.

Transcriptomic Profiling of Rectus Abdominis Muscle in Women with Gestational Diabetes-Induced Myopathy: Characterization of Pathophysiology and Potential Muscle Biomarkers of Pregnancy-Specific Urinary Incontinence.

Gestational diabetes mellitus (GDM) is recognized as a "window of opportunity" for the future prediction of such complications as type 2 diabetes mellitus and pelvic floor muscle disorders, including urinary incontinence and genitourinary dysfunction. Translational studies have reported that pelvic floor muscle disorders are due to a GDM-induced-myopathy (GDiM) of the pelvic floor muscle and rectus abdominis muscle (RAM). We now describe the transcriptome profiling of the RAM obtained by Cesarean section from GDM and non-GDM women with and without pregnancy-specific urinary incontinence (PSUI). We identified 650 genes in total, and the differentially expressed genes were defined by comparing three control groups to the GDM with PSUI group (GDiM). Enrichment analysis showed that GDM with PSUI was associated with decreased gene expression related to muscle structure and muscle protein synthesis, the reduced ability of muscle fibers to ameliorate muscle damage, and the altered the maintenance and generation of energy through glycogenesis. Potential genetic muscle biomarkers were validated by RT-PCR, and their relationship to the pathophysiology of the disease was verified. These findings help elucidate the molecular mechanisms of GDiM and will promote the development of innovative interventions to prevent and treat complications such as post-GDM urinary incontinence.

Streptozotocin-induced leukocyte DNA damage in rats.

Although several studies using peripheral blood samples suggest that DNA damage is caused by streptozotocin (STZ) per se, our hypothesis is that DNA damage is caused by STZ-induced glycemic changes. Thus, we aimed at evaluating DNA damage levels in peripheral blood samples from rats at different time points within the first 24 h after a single intravenous dose of STZ. Female Wistar rats (control, n = 8; STZ, n = 7) were administered a single STZ intravenous injection (40 mg/kg body weight). Blood samples were collected from the tail vein for genotoxicity analysis by comet assay and glycemia assessment before STZ administration (time point zero) and at 2, 4, 6, 8, 12, and 24 h afterward. At 2 h, there was initial hyperglycemia associated with STZ-induced glycogenolysis that caused an increase in leukocyte DNA damage levels. At 4 h, glycemic and DNA damage levels were normalized. However, at 6 and 8 h, we observed hypoglycemia concomitant with increased DNA damage levels. From 10 h onward up to 24 h, DNA damage persisted and hyperglycemia appeared. Thus, DNA damage increased soon after both hypoglycemia and hyperglycemia, which were not directly induced by STZ owing to its known short life. In conclusion, increased peripheral blood DNA damage levels within 24 h after STZ administration in rats are associated with abnormal glycemic levels and their complications rather than with STZ per se.

Effects of short-term severe and long-term mild STZ-induced diabetes in urethral tissue of female rats.

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.

Validation of a symphysis-fundal height chart developed for pregnancy complicated by diabetes and hyperglycemia: an observational study.

BACKGROUND: The present study validates a symphysis-fundal height chart (SFH-chart) for pregnant women with type 2 diabetes mellitus (DM2), gestational diabetes mellitus (GDM) and mild gestational hyperglycemia (MGH) attending at the Diabetes and Pregnancy Reference Service of the Botucatu Medical School, UNESP, Brazil. METHODS: A cross-sectional study was carried out to evaluate the performance of the specific FHC in predicting small (SGA) and large (LGA) for gestational age newborns (NB). We evaluated 206 pregnant women with DM2, GDM or MGH and their NB. The last symphysis-fundal height measure, taken at birth, was used to determine the sensitivity index (Sens), specificity index (Spe), positive prediction value (PPV), negative prediction value (NPV) and accuracy in predicting SGA and LGA. The gold standard was the Lubchenco birth weight/gestational age ratio evaluated at birth. RESULTS: The mothers showed adequate glycemic control; 91.3 % of all pregnant women achieved HbA1c < 6,5 % in the third trimester. The SFH-chart tested achieved 100 % of Sens and NPV in predicting both SGA and LGA, with accuracy of 90.3 % (85.5; 93.6) and 91.8 % (87.2; 94.8), respectively, for predicting SGA and LGA newborns. CONCLUSIONS: The Basso SFH-chart showed high performance in predicting both SGA and LGA newborns of DM-2, GDM and MGH mothers, with better performance than the national reference SFH-chart. These findings support the internal validation of the Basso SFH-chart, which may be implemented in the prenatal care of the Diabetes and Pregnancy Reference Service-Botucatu Medical School/UNESP.

Maternal and fetal outcomes in pregnancies complicated by overweight and obesity.

BACKGROUND: Overweight and obesity are associated with pregnancy complications and adverse perinatal outcomes, posing short and long-term risks for maternal and child health. This study evaluated maternal, delivery and neonatal outcomes in pregnancies complicated by overweight and obesity. METHODS: This prospective cross-sectional study included 258 pregnant women. According to prepregnancy body mass index (BMI), participants were classified as normal weight, overweight, or obese. Data were analyzed using the chi-square test and analysis of variance followed by the Tukey test. Logistic regression was performed to calculate odds ratios and 95 % confidence intervals (p < 0.05). RESULTS: Most women ≥ 35 years old were overweight (22.7 %) and obese (27.6 %). Prepregnancy diabetes was significantly associated with obesity (15.7 %, p < 0.000). Obese women showed the lowest weight gain (9.6 ± 7.5Kg). Overweight and obese women practiced physical exercise more frequently (p = 0.010) than normal weight women. A greater proportion of obese mothers (13.4 %) had large for gestational age babies (p = 0.021), with higher thoracic circumference (33.6 ± 2.0 cm) and abdominal circumference (31.6 ± 2.3 cm). Obesity increased the risk of developing hypertension (OR = 7.0; 3.1-15.9), hyperglycemic disturbances (OR = 5.5; 2.9-10.6) and HbA1c ≥ 6.5 % (OR = 3.7; 1.2-11.1). The infants born to obese mothers had longer hospital stay (3.9 ± 3.9 days) (p = 0.005). CONCLUSION: Our results confirm that obesity in pregnancy can lead to adverse outcomes, and underscore the importance of identifying and treating inadequate weight status during pregnancy.

Depression and anxiety in pregnant women with diabetes or mild hyperglycemia.

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.

Short and long-term repercussions of the experimental diabetes in embryofetal development.

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.

Urethral striated muscle and extracellular matrix morphological characteristics among mildly diabetic pregnant rats: translational approach.

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.

Risk factors for perinatal death in two different levels of care: a case-control study.

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.

Prognostic factors associated with time to hCG remission in patients with low-risk postmolar gestational trophoblastic neoplasia.

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.

The role of cytokines in the functional activity of phagocytes in blood and colostrum of diabetic mothers.

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- ß 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- ß 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- ß 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- ß modulate the functional activity of phagocytes in the colostrum, maternal blood, and cord blood of pregnant diabetic women.

Impact of Obesity and Hyperglycemia on Pregnancy-specific Urinary Incontinence.

OBJECTIVE: The lack of data on the impact of hyperglycemia and obesity on the prevalence of pregnancy-specific urinary incontinence (PSUI) led us to conduct a cross-sectional study on the prevalence and characteristics of PSUI using validated questionnaires and clinical data. METHODS: This cross-sectional study included 539 women with a gestational age of 34 weeks who visited a tertiary university hospital between 2015 and 2018. The main outcome measures were the prevalence of PSUI, the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), and the Incontinence Severity Index (ISI) questionnaires. The women were classified into four groups: normoglycemic lean, normoglycemic obese, hyperglycemic lean, and hyperglycemic obese. The differences between groups were tested using descriptive statistics. Associations were estimated using logistic regression analysis and presented as unadjusted and adjusted odds ratios. RESULTS: Prevalence rates of PSUI were no different between groups. However, significant difference in hyperglycemic groups worse scores for severe and very severe PSUI. When adjusted data for confound factors was compared with normoglycemic lean group, the hyperglycemic obese group had significantly higher odds for severe and very severe forms of UI using ICIQ-SF (aOR 3.157; 95% CI 1.308 to 7.263) and ISI (aOR 20.324; 95% CI 2.265 to 182.329) questionnaires and highest perceived impact of PSUI (aOR 4.449; 95% CI 1.591 to 12.442). CONCLUSION: Our data indicate that obesity and hyperglycemia during pregnancy significantly increase the odds of severe forms and perceived impact of PSUI. Therefore, further effective preventive and curative treatments are greatly needed.

OBJETIVO: A falta de dados sobre o impacto da hiperglicemia e obesidade na prevalência de incontinência urinária específica da gravidez (IAPS) nos levou a realizar um estudo transversal sobre a prevalência e características da IAPS usando questionários validados e dados clínicos. MéTODOS: Este estudo transversal incluiu 539 mulheres com idade gestacional de 34 semanas que visitaram um hospital universitário terciário entre 2015 e 2018. As principais medidas de desfecho foram a prevalência de PSUI, o formulário curto do International Consultation on Incontinence Questionnaire (ICIQ-SF) e os questionários do Incontinence Severity Index (ISI). As mulheres foram classificadas em quatro grupos: magras normoglicêmicas, obesas normoglicêmicas, magras hiperglicêmicas e obesas hiperglicêmicas. As diferenças entre os grupos foram testadas por meio de estatística descritiva. As associações foram estimadas usando análise de regressão logística e apresentadas como odds ratio não ajustadas e ajustadas. RESULTADOS: As taxas de prevalência de PSUI não foram diferentes entre os grupos. No entanto, houve diferença significativa nos grupos hiperglicêmicos com piores escores para PSUI grave e muito grave. Quando os dados ajustados para fatores de confusão foram comparados ao grupo magro normoglicêmico, o grupo obeso hiperglicêmico teve chances significativamente maiores de formas graves e muito graves de IU usando ICIQ-SF (aOR 3,157; IC 95% 1,308 a 7,263) e ISI (aOR 20,324; 95% CI 2,265 a 182,329) questionários e maior impacto percebido de PSUI (aOR 4,449; 95% CI 1,591 a 12,442). CONCLUSãO: Nossos dados indicam que a obesidade e a hiperglicemia durante a gravidez aumentam significativamente as chances de formas graves e o impacto percebido da PSUI. Portanto, tratamentos preventivos e curativos mais eficazes são extremamente necessários.

Integration of nutrigenomics, melatonin, serotonin and inflammatory cytokines in the pathophysiology of pregnancy-specific urinary incontinence in women with gestational diabetes mellitus.

Gestational diabetes mellitus is an important public health problem and has been associated with the development of pregnancy-specific urinary incontinence. The interaction is related to hyperglycemia, and inflammatory and hormonal patterns, which favor functional alterations in different organs and systems. Several genes associated with human diseases have been identified and partially characterized. Most of these genes are known to cause monogenic diseases. However, about 3 % of diseases do not fit the monogenic theory due to the complex interactions between multiple genes and environmental factors, as in chronic metabolic diseases such as diabetes. The nutritional, immunological, and hormonal patterns associated with changes in maternal metabolism may influence and contribute to greater susceptibility to urinary tract disorders. However, early systematic reviews have not yielded consistent findings for these associations. This literature review summarizes important new findings from integrating nutrigenomics, hormones, and cytokines in women with Gestational diabetes mellitus and pregnancy-specific urinary incontinence. Changes in maternal metabolism due to hyperglycemia can generate an inflammatory environment with increased inflammatory cytokines. This environment modulated by inflammation can alter tryptophan uptake through food and thus influence the production of serotonin and melatonin. As these hormones seem to have protective effects against smooth muscle dysfunction and to restore the impaired contractility of the detrusor muscle, it is assumed that these changes may favor the onset of urinary incontinence specific to pregnancy.

Influence of maternal hyperglycemia on IL-10 and TNF-α production: the relationship with perinatal outcomes.

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.

Influence of hydatidiform mole follow-up setting on postmolar gestational trophoblastic neoplasia outcomes: a cohort study.

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.

Molar pregnancy in adolescents.

OBJECTIVE: To describe the clinical presentation of hydatidiform molar pregnancy in women under the age of 20 years. In addition, we sought to understand if this adolescent population manifests differences in clinical factors compared to an adult population that may affect outcome. STUDY DESIGN: We used a database from the New England Trophoblastic Disease Center to analyze clinical data from all women followed for molar pregnancy between 1970 and 2009 with complete follow-up information. This population was stratified by age and clinical parameters including presenting signs, molar histology and development of gestational trophoblastic neoplasia (GTN). Univariable and multivariable logistic regression was employed to discern clinical factors that associated with adolescent age. The Partners Human Research Committee approved this study. RESULTS: We identified 1,494 women diagnosed with hydatidiform mole (HM), of which 220 (14.7%) were adolescents defined as age <20 years. The most common presenting clinical signs were vaginal bleeding and an enlarged uterus compared to dates. Median gestational age at diagnosis was 13.4 weeks, not different from that in the adult population. Similarly, no difference in presenting human chorionic gonadotropin was observed between the adult and adolescent populations. Adolescents presented with a significant overrepresentation of complete mole (86% vs. 75%, p < 0.001) compared to adults. Complete mole was associated with a heightened risk of developing GTN (OR 2.6, 95% CI 1.9-3.5), and despite the association of complete mole with young maternal age, univariable analysis showed no difference in the rate of GTN observed between adolescents and adults (24% vs. 30%, p = 0.08). Multivariable analysis controlling for molar histology demonstrated that adolescent age was associated with a decreased risk of GTN (hazard ratio 0.67, 95% CI 0.48-0.93). CONCLUSION: Adolescents account for a substantial proportion of the population with HM. They commonly present with vaginal bleeding. Though this population develops a complete mole with a higher frequency than adults, adolescents appear to have a significantly decreased risk of developing GTN.

Assessment of Pelvic Floor Disorders due to the Gestational Diabetes Mellitus Using Three-Dimensional Ultrasonography: A Narrative Review.

Gestational diabetes mellitus (GDM)is an entity with evolving conceptual nuances that deserve full consideration. Gestational diabetes leads to complications and adverse effects on the mother's and infants' health during and after pregnancy. Women also have a higher prevalence of urinary incontinence (UI) related to the hyperglycemic status during pregnancy. However, the exact pathophysiological mechanism is still uncertain. We conducted a narrative review discussing the impact of GDM on the women's pelvic floor and performed image assessment using three-dimensional ultrasonography to evaluate and predict future UI.

O diabetes gestacional (DG)é uma entidade com nuances conceituais em evolução que merecem total consideração. O DG leva a complicações e efeitos adversos na saúde da mãe e do bebê durante e após a gravidez. As mulheres também apresentam maior prevalência de incontinência urinária (IU) relacionada ao estado hiperglicêmico durante a gravidez. No entanto, o mecanismo fisiopatológico exato ainda é incerto. Realizamos uma revisão narrativa discutindo o impacto do DG no assoalho pélvico das mulheres e utilizamos o exame de ultrassonografia tridimensional para avaliar e predizer a ocorrência de IU.

Gestational diabetes is associated with alteration on pelvic floor muscle activation pattern during pregnancy and postpartum: Prospective cohort using electromyography assessment.

Background and objective: Gestational diabetes mellitus (GDM) is a comorbidity which may cause acute and lifelong disorders to mother and child. Alterations in muscular and connective tissues have been associated with GDM in translation studies, characterizing gestational diabetic myopathy. Pregnancy-specific urinary incontinence and sexual disabilities, disorders that depend on the pelvic floor muscle (PFM) integrity, are also associated with GDM both during and after pregnancy. The aim was to compare PFM activation patterns between GDM and non-GDM women from 24-30 gestational weeks to 18-24 months postpartum during a standard clinical test during gestation and postpartum. Methods: We conducted a prospective three-time-point cohort study from gestation (24-30 weeks-T1, and 36-38 weeks-T2) to 18-24 months postpartum (T3). PFM electromyography was recorded in primigravida or primiparous women with one previous elective c-section with or without the diagnosis of GDM according to the American Diabetes Association criteria. A careful explanation of the muscle anatomy and functionality of the PFM was given to participants before EMG assessment. The outcome measures were PFM activation patterns assessed during pregnancy and postpartum, comparing intra and between groups. PFM activation patterns were assessed by normalized electromyography signal at rest and during 1-second (sec) phasic, 10-sec hold, and 60-sec sustained contractions. Results: Demographic and obstetric data showed homogeneity between groups. The GDM group achieved peak PFM EMG amplitudes similarly to the non-GDM group, but they took longer to return to baseline levels during the ~1-sec contraction (flicks). During 10-sec hold contractions, the GDM group sustained lower levels of PFM activation than the non-GDM group at both 36-38 weeks of gestation and 18-24 months postpartum when compared to the non-GDM group. Conclusion: The results suggest that GDM impaired PFM control mainly on 1-sec flicks and 10-sec hold contraction, which appears to develop during late pregnancy and extends long-term postpartum. This motor behavior may play a role on pelvic floor dysfunctions.