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Objective: This study was conducted to investigate the distribution of placental villous vessels in pregnant women with different degrees of hyperglycemia., Methods: A cross-sectional study was performed using placental samples from 30 pregnant women without diabetes (n=10), with gestational diabetes mellitus (n=10), and with previous diabetes (type 1 and type 2 diabetes; n=10). Maternal glycemic control was evaluated using the glycemic mean and glycated hemoglobin levels. Placental samples were obtained during elective cesarean sections and processed for villous vessel analysis using immunohistochemistry for Von Willebrand factor. Vessels within 10μm of the villus margin were classified as peripheral, and vessels at a distance greater than 10μm were classified as central. The number, area, and perimeter of all vessels were evaluated, and the relationship between vessel area and total area of placental villus was calculated., Results: Pregnant women with gestational diabetes mellitus and those with previous diabetes had higher glycated hemoglobin levels. The number of vessels was reduced in the villi of the previous Diabetes Group owing to peripheral reduction. Additionally, the area, perimeter, and percentage of peripheral blood were lower in the previous Diabetes Group than in the Non-Diabetic Group., Conclusion: Maternal glycemic levels can modify placental capillary distribution.

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., Competing Interests: Declaration of competing interest I declare that I have no personal or pecuniary interest, direct or indirect, in any matter that raises or may conflict with my duties at the Institution., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors have no conflicts of interest to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Objective: To determine the occurrence and severity of pregnancy-specific urinary incontinence (PSUI) in women with gestational hyperglycaemia, and its impact on quality of life (QoL) over the first year post partum., Study Design: Three hundred and eighty-eight pregnant women with PSUI were distributed into two groups (normoglycaemic and hyperglycaemic) and analysed at five timepoints during pregnancy and the first year post partum. Gestational hyperglycaemia was defined according to the criteria of the American Diabetes Association and the glucose profile test. Relationships with outcome were analysed using Chi-squared test for categorical variables and Student's t-test for quantitative variables., Results: The overall prevalence rate of PSUI was 54.1 %, with prevalence rates of 43.3 % and 56.7 % in normoglycaemic and hyperglycaemic Brazilian pregnant women, respectively. Women with gestational hyperglycaemia had a higher amount of urine loss (p < 0.0027), frequency of UI (p < 0.0014), impact of UI on QoL (p < 0.0001), severity of UI (p = 0.0003) and total scores on the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-SF) and Incontinence Severity Index (ISI) (p<0.0001) at the two timepoints during pregnancy; and a higher amount of urine loss (p = 0.0079), frequency of UI (p = 0.0382), impact of UI on QoL (p < 0.0001), severity of UI (p = 0.0053) and questionnaire scores (p < 0.0001 for ICIQ-SF and p = 0.003 for ISI) over the first year post partum., Conclusions: PSUI in women with gestational hyperglycaemia worsens the occurrence and severity of UI, and the impact of UI on QoL over the first year post partum. These results emphasize the interaction between PSUI, gestational hyperglycaemia and long-term maternal outcome., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Reference symphysis-fundal height (SFH) curves for pregnancies complicated by maternal hyperglycemia are not available., Objective: To build an SFH curve according to gestational age for pregnant women with hyperglycemia-type 2 diabetes (T2DM), gestational diabetes mellitus (GDM), or mild gestational hyperglycemia (MGH) and compare it with three other curves in use in Brazil., Methods: Prospective cohort study of 422 pregnant women with hyperglycemia attending the Perinatal Diabetes Research Center (PDRC) of Botucatu Medical School, São Paulo State University/UNESP. Between 13 and 41 weeks of pregnancy, 2470 SFH measurements were obtained (mean 5.85 per woman). For the assessment of glycemic control, 2074 glucose level measurements were taken and the glycemic mean (GM) at each gestational week was estimated., Results: GM was adequate (<120 mg/dL) in 94.9% and inadequate (≥120 mg/dL) in 5.1% of the cases. The equation applied for SFH prediction was expressed as SFH = 1.082 + 0.966∗week ( r 2 = 84.6%). At visual analysis, P10 and P90 SFH measurements were higher in the study curve than in the three other curves. Statistical analysis confirmed that SFH median values in this study were higher than those in the reference curve of habitual risk pregnancies, especially after 19 weeks of pregnancy., Conclusion: Taking into account that the maternal hyperglycemia was at strict control, our unedited results suggest that the current SFH curve can be a useful tool in prenatal care of T2DM, GDM, and MGH pregnant women., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Neusa A. S. Basso et al.)

Mild gestational hyperglycemia (MGH), as assessed using the normal oral glucose tolerance test (OGTT) and detection of an altered glycemic profile, is associated with adverse perinatal outcome. This study described the results of 40 years of research conducted at the Perinatal Diabetes Research Centre at São Paulo State University (UNESP), Brazil, on the maternal MGH environment and placental markers. This study also described the unidirectional relationship between MGH and excessive fetal growth, also supplying moderator analysis. In addition to hyperglycemia, MGH is associated with an increased incidence of hypertension, metabolic syndrome, persistent insulin resistance after pregnancy, and high risk of developing type 2 diabetes mellitus (T2DM) after pregnancy. Structural changes and functional abnormalities resulting from MGH were observed in placenta. The fully adjusted model concluded that the predictor variable (MGH), which creates a complex environment for the fetus, has a direct effect on excessive birth weight and produces a z-score for ratios of birth weight to gestational age of ≥2. Maternal age, pre-pregnancy BMI, number of previous pregnancies, numbers of prenatal visits, and 1 h OGTT are moderator variables that impact MGH and excessive fetal growth. These results show that maternal MGH has some characteristics associated with similar long-term T2DM development and similar adverse perinatal results to those of gestational diabetes mellitus (GDM) mothers, making it an intermediate maternal and placental marker between normoglycemic and GDM mothers., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We investigated whether mitochondrial-related genes and proteins are modulated by hyperglycemia promoted by gestational diabetes (GDM), thereby increasing neonate obesity predisposition. 19 healthy pregnant women, 16 pregnant women with GDM and their respective neonates were enrolled. Additionally, 19 obese and 19 eutrophic adults were recruited as a reference population. Umbilical cord, peripheral blood and placental (villous and decidua) tissues were collected to evaluate SOD2, PPAR-α and PPARGC-1β and their respective protein expressions. Data from the reference population confirmed that the three genes and proteins were overexpressed in blood cells of obese compared to eutrophic subjects. Only SOD2 was found upregulated in placental villous (fetal side) tissue of GDM women. Therefore, our findings showed an interaction between the hyperglycemic environment and SOD2 modulation, but also indicated that none of the three genes is useful as potential biomarkers for obesity development., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This study was based on the hypothesis that IL-1β and its central regulator, the inflammasome, may play a role in the inflammatory condition exhibited by placental tissues from mothers with different gestational hyperglycemia levels. Pregnant women were classified according to the glycemic reference as non-diabetic (n = 15), mild gestational hyperglycemia (n = 15), gestational diabetes mellitus (n = 15) and type 2 diabetes mellitus (n = 15). We investigated levels of pro-inflammatory factors in maternal plasma and placental tissues (by ELISA or immunohistochemistry) and, NFKB activity (by electrophoretic mobility shift assay) and inflammasome protein expression (by Western blot) in chorionic villous. Maternal plasma and placental levels of inflammatory factors (IL-1β, IL-6, and MCP-1) were increased during all hyperglycemic conditions. Villous stroma cells showed strong immunoreactivity to CD68. In addition, with syncytiotrophoblast, the villous stroma cells were also stained to detect iNOS, MCP-1, TLR2, and TLR4. Although the levels of protein had fluctuated in the groups, NLRP1, NLRP3, ASC, and Caspase 1 were up-regulated in all hyperglycemic groups suggesting the inflammasome may be assembled in these pregnant women. The NFKB activity also exhibited higher levels in hyperglycemic groups, which might imply in pro-inflammatory cytokines production. In summary, increased maternal glucose levels during pregnancy changed systemic and placental inflammatory patterns, which occurred in parallel with the expression of inflammasome factors and processing and secretion of the pro-inflammatory cytokine IL-1β. These results suggest an inflammatory condition in all gestational hyperglycemic conditions, even in hyperglycemia that is less severe than gestational or overt diabetes, likely associated with inflammasome activation and inflammatory cytokine secretion. Inflammasome activation as a possible source of inflammatory factors may be an important target to be considered while managing hyperglycemia and preventing adverse pregnancy outcomes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To analyze the distribution and quantification of the key structural extracellular matrix components of the urethral tissue in a rat model of hyperglycemia and pregnancy., Study Design: A total of 120 female Wistar rats were distributed into the following four experimental groups: virgin, pregnant, hyperglycemic and hyperglycemic + pregnant groups. The urethra was harvested for histochemical, morphometric, immunohistochemical, Western blot and glycosaminoglycan analyses. All protocols were approved by the Institutional Animal Care and Use Committee of Botucatu Medical School (process number 828-2010)., Results: The hyperglycemic + pregnant group showed significantly increased stiffness in urethral tissue. The total striated muscle was decreased, with increased deposition of collagen fibers around the muscle fibers and a change in the organization of the collagen fibrils. An increase in the relative collagen type I/III ratio and a decrease in total glycosaminoglycans were also observed., Conclusions: This study provides the first line of experimental evidence supporting a metabolic relationship between hyperglycemia and urethral remodeling of connective tissue in pregnant rats. The different organization of the collagen fibrils and the profile of glycosaminoglycans found in urethral samples suggest that the pathology of the urethral fibromuscular system could be related to hyperglycemia-induced pelvic floor dysfunction in women, which has direct clinical implications with the possibility to develop new multidisciplinary treatments for improving the health care of these women., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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.