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We evaluated insulin release and insulin sensitivity in women with basal and/or postprandial hyperglycemia but normal oral glucose tolerance test (OGTT) in previous pregnancy (GHG). These women were individually matched with females without previous hyperglycemia (NGT). Both groups consisted of normal glucose-tolerant women at the time of this study. They underwent OGTT (75 g; n=32 pairs) and hyperglycemic clamp experiments (10 mmoll(-1); n=27 pairs) with plasma glucose, insulin, and C-peptide measurements and calculation of insulinogenic index, first- and second-phase insulin release, and insulin sensitivity index (ISI). The GHG group showed higher glycosylated hemoglobin levels (6.2+/-0.6% versus 5.8+/-0.8%; P<0.05); lower insulinogenic index at 30 min (134.03+/-62.69 pmol mmol(-1) versus 181.59+/-70.26 pmol mmoll(-1); P<0.05) and diminished C-peptide response in relation to glucose (4.05+/-0.36 nmol mmol(-1) versus 4.23+/-0.36 nmol mmol(-1); P<0.05) at OGTT. Both groups did not show difference in insulin secretion and ISI by hyperglycemic clamp technique. We concluded that in up to 12 years from index pregnancy, women with previous GHG, presenting normal glucose tolerance and well-matched with their controls, showed beta-cell dysfunction without change in ISI. As women with previous GHG are at risk of type 2 diabetes, beta-cell dysfunction may be its primary defect. [ABSTRACT FROM AUTHOR]

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.

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.

Background: Gestational Diabetes Mellitus (GDM) and many other clinical variables have been associated with postpartum urinary incontinence (UI). However, the data are still restricted, and no study explored early- or late-onset GDM as a risk factor for this condition. We aimed to identify independent risk factors for postpartum UI, focusing on GDM and its early or late onset., Methods: A nested case control derived from the Diamater cohort study included 517 pregnant women who submitted to a planned C-section and followed by 6-18 months after delivery according to the timing of GDM diagnosis: early-onset GDM (before 20 weeks) and late-onset GDM(24-28 weeks) and the occurrence of UI., Results: Univariate analysis showed that the risk for 6-18 months postpartum UI was 49% higher in non-Caucasian ethnicity (1.49,1.02-2.18), 3,3 times higher in previous bariatric surgery [3.37,1.36-8.21], 39% higher in GDM women (1.39,1.01-1.93), and 5% higher for each BMI score in prepregnancy (1.05, 1.03-1.08) and at the end of pregnancy (1.05,1.02-1.08). Multivariate logistic regression analysis indicates that prepregnancy BMI was the only independent factor associated with the 6-18 months postpartum UI (adj 1.05, 95 %CI 1.02-1.08, P <.001). After stratifying, a second univariate and multivariate analysis were done according to the prepregnancy BMI cutoff score of 25. Thus, a significant association between GDM and postpartum UI in prepregnancy overweight women (RR: 1.91; 95 %CI 1.25-2.90, P =.003) and no association between GDM and 6-18 months postpartum UI in normal prepregnancy BMI (RR: 0.78, 95 %CI 0.39-1.54, P =.482) were found. After multivariate regression, the early-onset-GDM remained the unique independent adjusted risk factor for 6-18 months postpartum UI analysis (adjRR 2.15, 95 %CI 1.33-3.46, P =.002)., Conclusion: After a planned C-section, we observed a 6-18 months postpartum UI higher occurrence after GDM, either in early-onset GDM or late-onset GDM. In addition, being overweight (BMI > 25) among women with early-onset GDM was associated with postpartum UI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Postpartum urinary incontinence may have a severe impact on women's health. Despite pregnancy and parturition being the most recognized risk factors, methods to identify new pregnant predictor risk factors are needed. Our study investigated the Gestational Diabetes Mellitus, clinical and pelvic floor 3D-ultrasound markers in pregnant women as predictors for 6-18 months of urinary incontinence. This prospective cohort study included nulliparous pregnant women submitted to Gestational Diabetes Mellitus screening in the second trimester. Pelvic floor 3D Ultrasound was performed at the second and third trimesters of gestation to evaluate the pelvic floor muscles and functions. Clinical data, the ICIQ-SF, and ISI questionnaires for urinary incontinence were applied in the third trimester and 6-18 months postpartum. Univariate analysis (P < .20) to extract risk factors variables and multivariate logistic regression analysis (P < .05) to obtain the adjusted relative ratio for urinary incontinence were performed. A total of 93 participants concluded the follow-up. Using the variables obtained by univariate analysis and after adjustments for potential confounders, multivariate analysis revealed that Gestational Diabetes Mellitus exposure was a solid and independent risk factor for 6-18 months of urinary incontinence (Adjusted RR 8.08; 95%CI 1.17-55.87; P:0.034). In addition, a higher Hiatal area observed in distension maneuver from the second to third trimester was negatively associated (Adjusted RR 0.96; 95%CI 0.93-0.99; P:0.023). In conclusion, Gestational Diabetes Mellitus was positively associated with 6-18 months of urinary incontinence, and higher Hiatal area distension was negatively associated., (© 2023. BioMed Central Ltd., part of Springer Nature.)

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/).)

The exposome is the cumulative measure of environmental influences and associated biological responses throughout the lifespan, including those from the environment, diet, behaviour, and endogenous processes. The exposome concept and the 2030 Agenda for the Sustainable Development Goals (SDGs) from the United Nations are the basis for understanding the aetiology and consequences of non-communicable diseases, including gestational diabetes mellitus (GDM). Pregnancy may be developed in an environment with adverse factors part of the immediate internal medium for fetus development and the external medium to which the pregnant woman is exposed. The placenta is the interface between maternal and fetal compartments and acts as a protective barrier or easing agent to transfer exposome from mother to fetus. Under and over-nutrition in utero, exposure to adverse environmental pollutants such as heavy metals, endocrine-disrupting chemicals, pesticides, drugs, pharmaceuticals, lifestyle, air pollutants, and tobacco smoke plays a determinant role in the development of GDM. This phenomenon is worsened by metabolic stress postnatally, such as obesity which increases the risk of GDM and other diseases. Clinical risk factors for GDM development include its aetiology. It is proposed that knowledge-based interventions to change the potential interdependent ecto-exposome and endo-exposome could avoid the occurrence and consequences of GDM., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Luis Sobrevia reports financial support was provided by Fondo Nacional de Desarrollo Científico y Tecnológico. Marilza Vieira Cunha Rudge reports financial support was provided by São Paulo Research Foundation (FAPESP)., (Copyright © 2022. Published by Elsevier B.V.)

Adipose tissue-derived mesenchymal stromal/stem cells (ASCs) are considered important tools in regenerative medicine and are being tested in several clinical studies. Porcine models are frequently used to obtain adipose tissue, due to the abundance of material and because they have immunological and physiological similarities with humans. However, it is essential to understand the effects and safe application of ASCs from pigs (pASCs) as an alternative therapy for diseases. Although minipigs are easy-to-handle animals that require less food and space, acquiring and maintaining them in a bioterium can be costly. Thus, we present a protocol for the isolation and proliferation of ASCs isolated from adipose tissue of farm pigs. Adipose tissue samples were extracted from the abdominal region of the animals. Because the pigs were not raised in a controlled environment, such as a bioterium, it was necessary to carry out rigorous procedures for disinfection. After this procedure, cells were isolated by mechanical dissociation and enzymatic digestion. A proliferation curve was performed and used to calculate the doubling time of the population. The characterization of pASCs was performed by immunophenotyping and cell differentiation in osteogenic and adipogenic lineages. The described method was efficient for the isolation and cultivation of pASCs, maintaining cellular attributes, such as surface antigens and multipotential differentiation during in vitro proliferation. This protocol presents the isolation and cultivation of ASCs from farm pig as an alternative for the isolation and cultivation of ASCs from minipigs, which require strictly controlled maintenance conditions and a more expensive process.

Background: Predictors of spontaneous preterm birth in primigravid women remain undetermined., Aim: We evaluated whether biomarkers in vaginal secretions and/or differences in the dominant bacterium in the vaginal microbiome predicted the risk for spontaneous preterm birth in primigravid women with a cervical length >25mm., Study Design: In a prospective study, 146 second trimester pregnant women with their first conception and a cervix >25mm were enrolled. The vaginal microbiome composition was characterized by analysis of 16S ribosomal RNA gene sequences. The concentrations of d- and l-lactic acid, matrix metalloproteinase (MMP) 2, 8 and 9 and tissue inhibitor of metalloproteinase (TIMP) 1 and 2 in vaginal secretions were measured by ELISA. Cervical length was determined by vaginal ultrasonography. Pregnancy outcome data were subsequently collected. There was a spontaneous preterm birth (SPTB) in 13 women (8.9%) while in an additional 8 women (5.5%) preterm delivery was medically indicated. Lactobacillus iners was the dominant vaginal bacterium in 61.5% of women with a SPTB but only in 31.2% of those who delivered at term ( p  = .0354). The vaginal concentration of TIMP-1 ( p  = .0419) and L-lactic acid ( p  = .0495) was higher in women with a SPTB as compared to those who delivered at term. Lactobacillus iners dominance was associated with elevated levels of TIMP-1 ( p  = .0434) and TIMP-2 ( p  = .0161) and lower levels of D-lactic acid ( p  < .0001) compared to when L. crispatus was dominant., Conclusion: In this exploratory study of primigravid women, elevations in vaginal TIMP-1 and L- lactic acid and L. iners dominance in the vaginal microbiome are associated with an increased occurrence of SPTB.

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., Competing Interests: The authors have no conflict of interests 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/).)

Induction of diabetes mellitus by streptozotocin (STZ) in rats at birth is of high mortality and low success rate when male puppies are separated from females, prioritizing females breastfeeding. Cross-parental care of the entire litter and SZT-induced diabetes up to 12 h post-birth become with high success rate, low animal death, and females with glycaemia >140 mg/dL on the 90 postnatal day. Cross-parental care is more effective in STZ-induction of diabetes, which is maintained during pregnancy (diabetes in pregnancy), than the conventional protocol of male separation at birth., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., (© 2022. The International Urogynecological Association.)

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.

Background: Ex-vivo myography enables the assessment of muscle electrical activity response. This study explored the viability of determining the physiological responses in muscles without tendon, as rectus abdominis muscle (RAM), through ex-vivo myography to assess its potential as a diagnostic tool., Results: All tested RAM samples (five different samples) show patterns of electrical activity. A positive response was observed in 100% of the programmed stimulation. RAM 3 showed greater weight (0.47 g), length (1.66 cm), and width (0.77 cm) compared to RAM 1, RAM 2, RAM 4 and RAM 5 with more sustained electrical activity over time, a higher percentage of fatigue was analyzed at half the time of the electrical activity. The order of electrical activity (Mn) was RAM 3 > RAM 5 > RAM 1 > RAM 4 > RAM 2. No electrical activity was recorded in the Sham group., Conclusions: This study shows that it is feasible to assess the physiological responses of striated muscle without tendon as RAM, obtained at C-section, under ex vivo myography. These results could be recorded, properly analyzed, and demonstrated its potential as a diagnostic tool for rectus abdominis muscle electrical activity., (© 2022. The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Prudencio, Nunes, Pinheiro, Sartorão Filho, Nava, Salomoni, Pedroni, Rudge, Barbosa and Diamater Study Group.)

Aim: This study aimed to assess, for the first time, the dynamic morphometry of pelvic floor muscles (PFM) using three-dimensional transperineal ultrasound (3D-TPUS) and its progression at two-time points of gestation between women with and without gestational diabetes mellitus (GDM), and whether the PFM dysfunction is connected to GDM., Methods: The study comprised 83 consecutive pregnant women with (n = 38) and without (n = 45) GDM screened at 24-30 and 38-40 weeks of gestation. 3D-TPUS and a mobility test were used to quantify PFM dynamic morphometry during maximum contraction and the Valsalva maneuver., Results: When compared to the control group, GDM women had no significant variations in all levator hiatal dimensions at 24-30 weeks of gestation. Meanwhile, women with GDM experienced an increase in levator hiatal area (LHa) (p < 0.000) during PFM contraction and enlargement in LHa (p < 0.001) during Valsalva maneuver (p = 0.010) at 38-40 weeks of gestation. As a result, the mobility index among GDM women had a lower value (p = 0.000). The dynamic morphometry development of PFM in GDM women at two stages during pregnancy revealed a substantial decrease (p = 0.000) in all LHa dimensions of contraction, distension, and mobility., Conclusions: Using 3D-TPUS, we found that GDM women had a specific pattern of PFM functional changes in the third trimester of pregnancy. These initial findings revealed alterations in PFM functionality, such as decreased contractility, distensibility, or mobility. This dysfunctional PFM could contribute to the long-term development of pelvic floor dysfunction years after a GDM pregnancy., (© 2022 Wiley Periodicals LLC.)

Gestational diabetes mellitus (GDM) plus rectus abdominis muscle (RAM) myopathy predicts long-term urinary incontinence (UI). Atrophic and stiff RAM are characteristics of diabetes-induced myopathy (DiM) in pregnant rats. This study aimed to determine whether swimming exercise (SE) has a therapeutic effect in mild hyperglycemic pregnant rats model. We hypothesized that SE training might help to reverse RAM DiM. Mild hyperglycemic pregnant rats model was obtained by a unique subcutaneous injection of 100 mg/kg streptozotocin (diabetic group) or citrate buffer (non-diabetic group) on the first day of life in Wistar female newborns. At 90 days of life, the rats are mated and randomly allocated to remain sedentary or subjected to a SE protocol. The SE protocol started at gestational day 0 and consisted of 60 min/day for 6 days/week in a period of 20 days in a swim tunnel. On day 21, rats were sacrificed, and RAM was collected and studied by picrosirius red, immunohistochemistry, and transmission electron microscopy. The SE protocol increased the fiber area and diameter, and the slow-twitch and fast-twitch fiber area and diameter in the diabetic exercised group, a finding was also seen in control sedentary animals. There was a decreased type I collagen but not type III collagen area and showed a similar type I/type III ratio compared with the control sedentary group. In conclusion, SE during pregnancy reversed the RAM DiM in pregnant rats. These findings may be a potential protocol to consider in patients with RAM damage caused by GDM., (© 2022. The Author(s).)

The angiogenesis process is a phenomenon in which numerous molecules participate in the stimulation of the new vessels' formation from pre-existing vessels. Angiogenesis is a crucial step in tissue regeneration and recovery of organ and tissue function. Muscle diseases affect millions of people worldwide overcome the ability of skeletal muscle to self-repair. Pro-angiogenic therapies are key in skeletal muscle regeneration where both myogenesis and angiogenesis occur. These therapies have been based on mesenchymal stem cells (MSCs), exosomes, microRNAs (miRs) and delivery of biological factors. The use of different calls of biomaterials is another approach, including ceramics, composites, and polymers. Natural polymers are use due its bioactivity and biocompatibility in addition to its use as scaffolds and in drug delivery systems. One of these polymers is the natural rubber latex (NRL) which is biocompatible, bioactive, versatile, low-costing, and capable of promoting tissue regeneration and angiogenesis. In this review, the advances in the field of pro-angiogenic therapies are discussed., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective:  To evaluate the effects of vitamin D supplementation in the postpartum period of women with previous gestational diabetes mellitus (GDM)., Methods:  Randomized clinical trials of pregnant women with GDM of any chronological, gestational age and parity, with no history of previous disease who received vitamin D supplementation in the prenatal and/or postpartum period and were evaluated in the postpartum period were included. The PubMed, EMBASE, Cochrane, and LILACS databases were consulted until July 2019. Serum vitamin D concentration (25-hydroxyvitamin D in nmol/L), fasting blood glucose, glycated hemoglobin, serum calcium concentration, homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), parathyroid hormone (PTH) and body mass index (BMI) were evaluated. Similar results in at least two trials were plotted using the RevMan 5; Cochrane Collaboration, Oxford, Reino Unido. The quality of the evidence was generated according to the classification, development, and evaluation of the classification of the recommendations., Results:  Four studies were included in the present review (200 women). The findings indicate that there is no difference in the postpartum period in women diagnosed with previous GDM who received vitamin D supplementation in the prenatal and/or in the postpartum period, showing only that there was a significant increase in the concentration of vitamin D (relative risk [RR]: 1.85; 95% confidence interval [CI]: 1.02-2.68)., Conclusion:  This increase in the concentration of vitamin D should be interpreted with caution, since the assessment of the quality of the evidence was very low. For the other analyzed outcomes, there was no significance between the intervention and control groups, and the outcomes, when analyzed in their strength of evidence, were considered very low and low in their evaluation., Competing Interests: The authors have no conflict of interests 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/).)

Wounds can take longer to heal in diabetic patients, increasing the risk of infections and other complications. The most common wounds in diabetic patients are diabetic foot ulcers, a severe complication associated with diabetes mellitus. The United States alone spends $18.7 billion annually on care for these wounds including pain and infection management. If improperly managed, infected lesions may require amputation. The enormous cost associated with wound care and the dire consequences if not cared for properly, emphasize the need to develop strategies to accelerate the healing of diabetic foot wounds. Natural rubber latex (NRL), extracted from Hevea brasiliensis (the rubber tree), has been widely applied as a carrier system for several pharmacologically active compounds. Furthermore, it has been shown to encourage angiogenesis, facilitate cell adhesion, and accelerate wound healing. When NRL dressings are applied to wounds of diabetic patients, exudate release is upregulated. The production of exudate is essential to wound healing as it provides the nutrients, proteins, cells, and environment required for regeneration. Despite its benefits, it is necessary to control excess exudate to avoid prolonged healing resulting from dermatitis, maceration of the wound edges, and lesion growth. In order to solve the problem of excessive exudate release induced by NRL membrane application, we aimed to regulate humidity by absorbing excess exudate and increase water vapor transmission. We developed a highly absorptive, permeable, alginate loaded NRL dressing. Adding alginate to NRL membranes, swelling was increased up to 80-fold, absorbing 4.80 g of water per gram of dry membrane. Moreover, water vapor transmission was improved drastically as the material transmitted 480% more water vapor than pure NRL membranes. Furthermore, in vitro tests demonstrated not only that the membranes are biocompatible, but that they also enhance cell proliferation. Through a cell proliferation assay, we observed that fibroblast proliferation was improved by the presence of NRL while the keratinocytes benefit from the presence of alginate. The NRL-alginate dressings have great potential to improve diabetic wound care by accelerating the healing process., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: There is ample evidence that gestational diabetes mellitus has a direct influence on urinary incontinence and pelvic floor muscles. There are no standardized pelvic floor muscle exercise programs in the literature for the physiotherapy and differ in the type of exercise, intensity, type and duration of application, and the frequency and duration of treatment sessions. The aim of this systematic review will be to investigate that Pelvic Floor Muscle Training can prevent and/or decrease the pregnancy specific urinary incontinence in women with gestational diabetes mellitus or gestational hyperglycemia., Methods: We will perform a systematic review according to the Cochrane methodology of Randomized Controlled Trials. An overall search strategy will be developed and adapted for Embase, MEDLINE, LILACS, and CENTRAL databases, with the date of consultation until June 2020. The MeSH terms used will be "Pregnancy", "Hyperglycemia", "Diabetes Mellitus, Type 2", "Diabetes Mellitus, Type 1", "Pregnancy in Diabetics", "Diabetes, Gestational", "Urinary Incontinence", "Pelvic Floor Muscle Strength". Primary outcomes: improvement or cure of pregnancy specific urinary incontinence (which can be assessed by questionnaires, and tools such as tampon test, voiding diary, urodynamic study). Secondary outcomes: improvement of pelvic floor muscle strength (pelvic floor functional assessment, perineometer, electromyography, functional ultrasonography), improved quality of life (questionnaires), presence or absence of postpartum Urinary Incontinence and adverse effects. Quality assessment by Cochrane instrument. Metanalysis if plausible, will be performed by the software Review Manager 5.3., Discussion: The present study will be the first to analyze the effectiveness of pelvic floor exercises in pregnant women with Gestational Diabetes Mellitus or Hyperglycemia, who suffer from pregnancy specific urinary incontinence. Randomized Controlled Trials design will be chosen because they present the highest level of evidence. It is expected to obtain robust and conclusive evidence to support clinical practice, in addition to promoting studies on the theme and contributing to new studies., Trial Registration: Systematic review registration: PROSPERO CRD42017065281., Competing Interests: The authors have declared that no competing interests exist.

Aim: To evaluate the pelvic floor (PF) biometry using three-dimensional ultrasound (US) at two-time points of gestational in pregnant women with gestational diabetes mellitus (GDM)., Methods: A prospective cohort study conducted at the Perinatal Diabetes Research Center including 44 pregnant women with GDM and 66 pregnant women without GDM at 24 to 28 weeks of gestation. Three-dimensional transperineal US was performed at 24 to 28 and 34 to 38 weeks of gestation in the lithotomy position at rest. The axial plane of the minimal Levator hiatal dimensions was used to determine Levator ani muscle and Hiatal area (HA) biometry at 24 to 28 and 34 to 38 weeks of gestation., Results: Of the 110 pregnant women, 100 (90.9%) completed the follow-up at 34 to 38 weeks of gestation. The evaluation by US showed a negative biometric change between the two-time points, during pregnancy in women with GDM; in the HA (β coefficient: estimative of effect in biometric progression according to GDM diagnosis, using the non-GDM group as reference = -6.76; P = .020), anteroposterior diameter (β = -5.07; P = .019), and Levator ani thickness (β = -12.34; P = .005)., Conclusions: Pregnant women with GDM had a significantly lower than expected percentage of changes in biometry of Levator ani thickness and HA from 24 to 28 to 34 to 38 weeks of gestation when compared with the group of pregnant women without GDM. GDM alters the morphology of PF structures assessed by three-dimension US. This reported complication may be implicated in adverse birth outcomes and may play a role in the development of PF dysfunction., (© 2020 Wiley Periodicals LLC.)

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.)

Aims: To evaluate the effects of gestational diabetes mellitus (GDM) on the structural characteristics of the rectus abdominis muscle (RAM) and its indirect effects on pregnancy-specific urinary incontinence (PSUI)., Methods: A total of 92 pregnant women were divided into four groups, according to their clinical conditions: non-GDM continent, non-GDM associated PSUI, GDM continent and GDM associated PSUI. The muscle morphometry (histochemistry and immunohistochemistry) for the fiber types and collagen fiber distribution, the ultrastructural analysis (transmission electron microscopy), the protein expression of fiber types and calcium signaling (Western blotting), and the content of types I and III collagen fiber (ELISA) in RAM collected at delivery were assessed., Results: The GDM groups presented a significantly increased number of slow fibers and slow-twitch oxidative fiber expression; decreased fiber area, number of fast fibers, and area of collagen; an increase in central nuclei; ultrastructural alterations with focal lesion areas such as myeloid structures, sarcomere disorganization, and mitochondrial alteration. The PSUI groups presented a considerable decrease in types I and III collagen contents and the localization of collagen fiber., Conclusions: Our data reveal that GDM causes morphological, biochemical and physiological changes in the RAM, and this might predispose women to PSUI., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide, and this condition may be compromising female sexual function. However, there are controversial findings regarding the impact of GDM diagnosis and proposed treatments on sexual function during pregnancy. Therefore, this study seeks to elucidate the impact of GDM on sexual function in pregnant women by making a comparison between GDM and non-GDM groups using pregnancy sexual response inventory (PSRI). Materials and Methods: A case-control study involved 303 [168 women without GDM (control group) and 108 women diagnosed with GDM (case group)] Brazilian pregnant women at the Perinatal Diabetes Research Centre-Universidade Estadual Paulista, Brazil. PSRI was used to collect the data. The sexual function was scored in 10 domains as composite and specific scores by domains, categorized into quartiles (0 < 25 "very low," 25 < 50 "low," 50 < 75 "high," and 75-100 "very high"), for "before pregnancy" and "during pregnancy." The obtained data were subjected to statistical analysis using Student's t -, F -, and chi-square tests. Results: GDM women (PSRI composite score <50) are at risk of decreased sexual function during pregnancy, while non-GDM women are not at risk (PSRI composite score >50). There were no significant differences in the sexual functions between the two groups before pregnancy ( p  > 0.0001). After GDM diagnosis and proposed treatment, the differences were significant ( p  < 0.0001), notably in the frequency, arousal, orgasm, satisfaction, and dyspareunia score. Conclusions: This study showed that GDM diagnosis and proposed treatment resulted in decreased sexual functions during pregnancy.

Background: While sufficient evidence supporting universal screening is not available, it is justifiable to look for specific risk factors for gestational diabetes mellitus (GDM) or hyperglycemia in pregnancy (HIP). The objective of this study is to identify independent risk factors for HIP and its adverse perinatal outcomes in a Brazilian public referral center., Methods: We included 569 singleton pregnant women who were split into three groups by glucose status: GDM (n = 207), mild gestational hyperglycemia (MGH; n = 133), and control (n = 229). Women who used corticosteroids or had a history of DM were excluded. HIP comprised both GDM and MGH, diagnosed by a 100 g- or 75 g-oral glucose tolerance test (OGTT) and a glucose profile at 24-28 weeks. Maternal characteristics were tested for their ability to predict HIP and its outcomes. Bivariate analysis (RR; 95% CI) was used to identify potential associations. Logistic regression (RR adj ; 95% CI) was used to confirm the independent risk factors for HIP and its perinatal outcomes ( p  < 0.05)., Results: Age ≥ 25 years [1.83, 1.12-2.99], prepregnancy BMI ≥ 25 kg/m 2 [2.88, 1.89-4.39], family history of DM [2.12, 1.42-3.17] and multiparity [2.07, 1.27-3.37] were independent risk factors for HIP. Family history of DM [169, 1.16-2.16] and hypertension [2.00, 1.36-2.98] were independent risk factors for C-section. HbA1c ≥ 6.0% at birth was an independent risk factor for LGA [1.99, 1.05-3.80], macrosomia [2.43, 1.27-4.63], and birthweight Z-score > 2.0 [4.17, 1.57-11.10]., Conclusions: MGH presents adverse pregnancy outcomes similar to those observed in the GDM group but distinct from those observed in the control (no diabetes) group. In our cohort, age ≥ 25 years, prepregnancy BMI ≥ 25 kg/m 2 , family history of DM, and multiparity were independent risk factors for HIP, supporting the use of selective screening for this condition. These results should be validated in populations with similar characteristics in Brazil or other low- and middle-income countries., Competing Interests: Competing interestsThe authors declare that partial data from this study were previously published [11]., (© The Author(s) 2020.)

Background and Objective: In the present study, we compared the effect of diabetic pregnancy on the rectus abdominis muscle (RAM) in humans and rats. We hypothesized that our animal model could provide valuable information about alterations in the RAM of women with Gestational Diabetes (GDM)., Method: Newborns female rats (n = 10/group) were administered streptozotocin (100 mg/kg body weight) subcutaneously and were mated on reaching adulthood, to develop the mild hyperglycemic pregnant (MHP) rat model. At the end of pregnancy, the mothers were sacrificed, and the RAM tissue was collected. Pregnant women without GDM (non-GDM group; n = 10) and those diagnosed with GDM (GDM group; n = 8) and undergoing treatment were recruited, and RAM samples were obtained at C-section. The RAM architecture and the distribution of the fast and slow fibers and collagen were studied by immunohistochemistry., Results: No statistically significant differences in the maternal and fetal characters were observed between the groups in both rats and women. However, significant changes in RAM architecture were observed. Diabetes in pregnancy increased the abundance of slow fibers and decreased fast fiber number and area in both rats and women. A decrease in collagen distribution was observed in GDM women; however, a similar change was not observed in the MHP rats., Conclusion: Our results indicated that pregnancy- associated diabetes- induced similar structural adaptations in the RAM of women and rats with slight alterations in fiber type number and area. These findings suggest that the MHP rat model can be used for studying the effects of pregnancy-associated diabetes on the fiber structure of RAM., Competing Interests: The authors have declared that no competing interests exist.

Gestational diabetes Mellitus (GDM) is a complex clinical condition that promotes pelvic floor myopathy, thus predisposing sufferers to urinary incontinence (UI). GDM usually regresses after birth. Nonetheless, a GDM history is associated with higher risk of subsequently developing type 2 diabetes, cardiovascular diseases (CVD) and UI. Some aspects of the pathophysiology of GDM remain unclear and the associated pathologies (outcomes) are poorly addressed, simultaneously raising public health costs and diminishing women's quality of life. Exosomes are small extracellular vesicles produced and actively secreted by cells as part of their intercellular communication system. Exosomes are heterogenous in their cargo and depending on the cell sources and environment, they can mediate both pathogenetic and therapeutic functions. With the advancement in knowledge of exosomes, new perspectives have emerged to support the mechanistic understanding, prediction/diagnosis and ultimately, treatment of the post-GMD outcomes. Here, we will review recent advances in knowledge of the role of exosomes in GDM and related areas and discuss the possibilities for translating exosomes as therapeutic agents in the GDM clinical setting., Competing Interests: The authors declare no conflict of interest.

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 .

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.

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.)

Objective: to understand the satisfaction of pregnant women with diabetes who took insulin during pregnancy and prenatal care performed through outpatient and inpatient follow-up., Method: a qualitative approach with analysis of 30 pregnant women who underwent prenatal care and participated in a clinical trial study carried out by the research group of the Perinatal Diabetes Research Center of the Hospital das Clínicas, of the Faculdade de Medicina de Botucatu. The data were collected through interviews and analyzed from content analysis., Results: from the category Satisfaction, the following subcategories emerged: facilities and difficulties faced in prenatal care performed through outpatient or inpatient follow-up, demonstrating that the pregnant women were satisfied with the prenatal care offered regardless of the type of follow-up., Conclusion: there was satisfaction in both care, but in outpatient care some structural, technical and administrative difficulties were identified, requiring reassessment, in order to guarantee service agility.

There is an ongoing discussion regarding abdominal muscle (AbM) and pelvic floor muscle (PFM) synergism. Therefore, this study aimed to investigate the cocontraction between AbMs and PFMs in women with or without pelvic floor dysfunction (PFD). The following databases were searched up to December 21, 2018: MEDLINE, EMBASE, LILACS, PEDro and CENTRAL. We included any study that assessed the cocontraction between PFMs and AbMs in women with and without PFD. Two reviewers independently screened eligible articles and extracted data. The outcomes were extracted and analyzed as continuous variables with random effect models. Twenty studies were included. A meta-analysis did not show differences in women with and without PFD. However, a sensitivity analysis suggested cocontraction of the transversus abdominis (TrA) during PFM contraction in healthy women (standardized mean difference (SMD) -1.02 [95% confidence interval (CI) -1.90 to -0.14], P=0.02; I2= not applicable; very low quality of evidence). Women with PFD during contraction of PFMs showed cocontraction of the obliquus internus (OI) (SMD 1.10 [95% CI 0.27 to 1.94], P=0.01; I2= not applicable; very low quality of evidence), and obliquus externus (OE) (SMD 2.08 [95% CI 1.10 to 3.06], P<0.0001; I2 = not applicable; very low quality of evidence). Increased cocontraction of the TrA may be associated with maximal contraction of PFMs in women without PFD. On the other hand, there is likely an increased cocontraction with the OI and OE in women with PFD.

Background and Objective: Pelvic floor muscles are involved in postural stability, in maintenance intra-abdominal pressure, and on mechanical support for pelvic organ. Gestational Diabetes Mellitus' (GDM) pregnancies complicated by fetal macrosomia, large placenta and polyhydramnios contribute for abrupt and intense increase in maternal intra-abdominal pressure. Our objective was analyze the impact of GDM on pelvic floor muscle (PFM) electromyography (EMG) activity progress from 24-30 to 36-38 weeks of gestation. We conducted a prospective cohort study. PFM EMG was performed in nulliparous or primiparous women with one previous elective cesarean delivery and with or not GDM diagnosed by the American Diabetes Association criteria. A careful explanation of the muscle anatomy and functionality of the PFM was given before EMG assessment. The outcome measures were PFM recruitment and progress from 24-30 to 36-38 weeks of gestation analyzed by the normalized root mean square (RMS) during rest-activity, fast and hold pelvic floor muscle contraction., Results: Fifty-two pregnant women were assigned to 2 groups: the GDM (n = 26) and normoglycemic (NG) (n = 26). The demographic and obstetric data showed homogeneity between the groups. PFM activity progress was decreased in rest-activity (P = 0.042) and hold contraction (P = 0.044) at 36-38 weeks of gestation in the GDM group relative to that in the NG group., Conclusion: GDM group showed a progressive decrease in EMG-PFM activity during rest-activity and hold contractions from 24-30 to 36-38 weeks of gestation., Competing Interests: The authors have declared that no competing interests exist.

In many impoverished regions of the world, it may not be possible to assess two major risk factors for preterm birth: a short cervical length and the depletion of vaginal lactobacilli. We determined whether measuring specific compounds in vaginal fluid might be a simple, noninvasive, and cost-effective way to predict the bacteria that dominate the vaginal microbiome and indicate the presence of a shortened cervix (<25 mm). Vaginal fluid samples were prospectively collected from mid-trimester pregnant women, and the concentrations of d- and l-lactic acid, tissue inhibitor of matrix metalloproteinases TIMP-1 and TIMP-2, matrix metalloproteinases MMP-2 and MMP-8, the 70-kDa heat shock protein, a2 isoform of vacuolar ATPase, and sequestrome-1 were quantified by an enzyme-linked immunosorbent assay (ELISA). The compositions of vaginal microbiomes were assessed by analysis of the V1-V3 regions of 16S rRNA genes, while cervical length was determined by transvaginal ultrasonography. The vaginal microbiomes could be clustered into five community state types (CSTs), four of which were dominated by a single Lactobacillus species. The dominance of Lactobacillus crispatus or Lactobacillus jensenii in the vaginal microbiome predicted the level of d-lactic acid present. Several of the biomarkers, especially TIMP-1, in combination with the subject's age and race, were significantly associated with cervical length. Using piecewise structural equation modeling, we established a causal network that links CST to cervical length via biomarkers. We concluded that measuring levels of TIMP-1 and d-lactic acid in vaginal secretions might be a straightforward way to assess the risk for preterm birth due to a short cervix and microbiome composition. IMPORTANCE Premature birth and its complications are the largest contributors to infant death in the United States and globally. A short cervical length and the depletion of Lactobacillus species are known risk factors for preterm birth. However, in many resource-poor areas of the world, the technology to test for their occurrence is unavailable, and pregnant women with these risk factors are neither identified nor treated. In this study, we used path analysis to gain an unprecedented understanding of interactions between vaginal microbiome composition, the concentrations of various compounds in vaginal secretions, and cervical length. We identified low-cost point-of-care measures that might be used to identify pregnant women at risk for preterm birth. The use of these measures coupled with appropriate preventative or treatment strategies could reduce the incidence of preterm births in poor areas of the world that lack access to more sophisticated diagnostic methods., (Copyright © 2019 Witkin et al.)

The diabetic syndrome affects pregnancy, contributing to placental functional and structural disruptions and impaired fetal development, with many reports indicating tobacco-associated morbidity and perinatal mortality. In our study, an experimental rat model of diabetes and cigarette smoke exposure in pregnant rats was used to determine the impact of the combination of diabetes and exposure to cigarette smoke during pregnancy on maternal oxidative stress biomarkers and placental and fetal development. Diabetes was induced by streptozotocin, and dams were exposed to cigarette smoke by mainstream smoke generated by a mechanical smoking device and delivered into a chamber. Four groups of dams were studied: nondiabetic (C, control) and diabetic (D) exposed to filtered air and nondiabetic (CS) and diabetic (DS) exposed to cigarette smoke prior to and during pregnancy. Maternal oxidative stress biomarkers, placental morphology, and fetal growth were determined close to term. The combination of diabetes and cigarette smoke resulted in elevated maternal blood glucose levels and increased number of small fetuses. Placentas from the DS group showed increased junctional zone and decreased labyrinthine area. The morphological alterations were characterized by extensive vascular congestion, thickness, and hyalinization of the vascular walls, numerous decidual cells with abundant glycogen, and macrophages with cytoplasmic inclusions of hemosiderin. Additionally, they showed increased glycogen accumulation and junctional zone structural derangement with ectopic giant cells. No alterations were observed in maternal oxidative stress status. Thus, our result suggests that diabetes makes pregnant rats more susceptible to the adverse effects of exposure to cigarette smoke on placental morphometry and fetal growth.

Background: Hysterectomy for benign gynecologic diseases, especially dysfunctional uterine bleeding, is one of the most common gynecologic interventions. The uterus can be removed using abdominal, vaginal, laparoscopic, or robotic-assisted laparoscopic hysterectomy. In a robotic-assisted procedure, the surgeon directs the robot while seated at a console in the operating room. This differs from laparoscopic hysterectomy because a "robot" performs the operation, while the surgeon watches a monitor. This systematic review will compare quality of life (QOL) in patients who undergo total robotic-assisted laparoscopic hysterectomy for benign indications and those who undergo conventional laparoscopic surgery., Methods: We will perform a systematic review according to the Cochrane Methodology for randomized controlled trials. The review will include studies reporting use of QOL metrics to assess patients who undergo total hysterectomy for benign indications using robotic-assisted technique or conventional laparoscopic surgery. QOL will be the primary outcome and will be measured using validated instruments. An overall search strategy will be developed and adapted for Embase, MEDLINE, LILACS, and CENTRAL databases. Two reviewers will independently select the eligible studies, assess the risk of bias, and extract the data from included studies. Similar outcomes measured in at least 2 trials will be plotted in the meta-analysis using Review Manager 5.3. The quality of evidence will be determined using the GRADE approach., Results: This systematic review is designed to provide high quality evidence on QOL in patients undergoing total hysterectomy for benign indications using either robotic-assisted or conventional laparoscopic surgery., Conclusion: It is expected that high-quality evidence on QOL can be used to guide decision-making by institutions and clinicians to improve health care; the evidence can also be used in future studies., Prospero Registration Number: PROSPERO CRD 42019129913.

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.)

Background: Trials have examined on the benefits of vitamin D supplementation in pregnant women., Objective: This review aimed to evaluate whether oral vitamin D supplements, when given to pregnant women with gestational diabetes mellitus (GDM), would improve maternal and neonatal outcomes, compared with no treatment or placebo., Method: We performed a systematic review following Cochrane methodology, and randomized trials were included where pregnant women with GDM received vitamin D supplementation versus placebo/no treatment or vitamin D and calcium versus placebo/no treatment. Primary outcomes were preeclampsia, preterm birth, cesarean delivery, gestational hypertension, and adverse events related to vitamin D supplementation. The search strategies were applied to the following databases: MEDLINE, Embase, LILACS, and CENTRAL. Similar outcomes in at least two trials were plotted using Review Manager 5.3 software. The quality of evidence was generated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)., Results: The total of 1224 references were identified, eleven trials were potentially eligible, and six were included in this review (totaling 456 women). The meta-analysis of frequency of cesarean deliveries did not show significant differences between groups, none of the trials evaluated the remaining primary outcomes. For secondary outcomes, our results suggest that vitamin D supplementation in pregnant women with GDM may reduce newborn complications such as hyperbilirubinemia, polyhydramnios (RR: 0.40, 95% CI: 0.23 to 0.68; RR: 0.17, 95% CI: 0.03 to 0.89; respectively), and the need for maternal or infant hospitalization (RR: 0.13; 95% CI: 0.02 to 0.98; RR: 0.40, 95% CI: 0.23 to 0.69). However, the evidence was of low or very low quality., Conclusion: We did not find moderate or high quality evidence indicating that vitamin D supplementation, when compared with placebo, improves glucose metabolism, adverse maternal and neonatal outcomes related to GDM in pregnant women., Competing Interests: The authors have declared that no competing interests exist.

Background and Objective: Gestational diabetes mellitus (GDM) is associated with short- and long-term maternal and perinatal repercussions. Our objective was to evaluate the long-term consequences of intrauterine exposure to hyperglycemia on Developmental Defects of Enamel (DDE) in offspring., Results: Overall, 50 children of women with GDM and 250 children of normoglycemic women participated, the latter serving as controls. Children were examined at the age between 3 and 12 years. In addition to physical examination, two independent observers examined and rated photographs to identify specific types of DDE in a blinded fashion. Among offspring of mothers with GDM, rates of DDE (all types combined) and hypoplasia (specific type) were significantly higher (p<0.001, p = 0.04), in comparison to offspring of normoglycemic mothers. Considering only the affected teeth (1060 in GDM category; 5499 in controls), rates of DDE (all types combined) were significantly higher for total teeth (p <0.001) and deciduous teeth (p<0.001), but not permanent teeth. In specific types of DDE involving deciduous teeth, rates of demarcate opacity were significantly higher (p<0.001; canine and 2nd mandibular molars) and hypoplasia (p <0.001; 2nd maxillary molars and 2nd mandibular molars). In permanent teeth, the rate of diffuse opacity in association with GDM was significantly higher (p<0.001; maxillary central incisors and 1st maxillary molars)., Conclusion: GDM was associated with the adverse effects of DDE on offspring. This study lays the foundation for future studies to determine the impact of GDM on long-term risk of DDE., Competing Interests: The authors have declared that no competing interests exist.

Several findings suggest that in utero stressor stimuli can alter fetal development by promoting transcriptional changes, and predisposing the neonate to diseases later in life. This study aimed to investigate whether a hyperglycemic environment in pregnant women with gestational diabetes mellitus (GDM) is able to cause fetal genetic alterations and predispose neonates to obesity. Transcriptional alteration of SIRT1, TP53 and BCL2 genes, miR-181a (a SIRT1 or BCL2 regulator) and telomere length were evaluated in placental and umbilical-cord blood cells. Healthy (HP; n = 20) and GDM (n = 20) pregnant women and their respective neonates were included in the study. Additionally, obese (n = 20) and eutrophic (n = 20) adults also participated as reference populations. Gene expression data showed down-regulation of BCL2 in umbilical-cord and peripheral blood cells from GDM neonates and obese adults, respectively. The miR-181a was down-regulated only in umbilical-cord blood cells of GDM neonates. Telomere length presented no significant difference. In conclusion, our study demonstrated that the GDM hyperglycemic intrauterine environment promotes transcriptional alterations in BCL2 and miR-181a in neonate umbilical-cord blood cells. Furthermore, both GDM neonates and obese subjects share the same transcriptional alteration in BCL2. Considering the relationship between obesity development and the functions regulated by these two genes, BCL2 and miR-181a could be adopted as potential biomarkers for childhood obesity. However, further study designs are recommended to confirm this hypothesis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Fetal impairment caused by a deleterious intrauterine environment may have long-term consequences, such as oxidative stress and genetic damage. Rats born as small-for-gestational-age (SPA) were submitted to exercise (swimming) before and during pregnancy. The animals exhibited glucose intolerance, reduced general adiposity, and increased maternal and offspring organ weight, showing the benefit of exercise for these rats. We hypothesised that regular exercise in SPA during gestation could prevent DNA damage in these animals and in their offspring, contributing to altered fetal programming of metabolism in the offspring. Severe diabetes was induced by streptozotocin treatment, to obtain SPA newborns. At adulthood, pregnant SPA rats were randomly distributed into two groups: exercised (SPAex - submitted to swimming program) or not-exercised (SPA - sedentary rats). Post-partum, blood was collected for analysis of DNA damage (comet assay) and oxidative stress. SPAex rats presented lower DNA damage levels, decreased lipid peroxidation, and a lower rate of newborns classified as large-for-pregnancy-age. DNA damage was also lower in SPAex newborns. We conclude that swimming applied to SPA pregnant rats contributes to decreased DNA damage and lipid peroxidation in the dams, and decreased DNA damage and macrosomia in their offspring., (Copyright © 2018 Elsevier B.V. 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.)

Antenatal stress is linked to fetal risks that increase the chances of neonatal complications and reduction of child cognitive ability. Therefore, we aimed to evaluate if maternal stress affects fetal, neonatal or child development. The following databases were searched: MEDLINE (1966 to May 2016), Embase (1980 to May 2016), LILACS (1982 to May 2016) and CENTRAL (1972 to May 2016). Observational studies published in English and Portuguese were included whether there was any relationship between fetal and neonatal outcome, such as birth weight, preterm labor, child development with pregnant women that were subjected to any stress type during at least one month of follow-up. Two independent reviewers screened eligible articles, extracted data and assessed the risk of bias. Thus, 8 cohort studies with about 8,271 pregnant women and 1,081,151 children proved eligible. Results suggested a significant association between antenatal stress exposure and increasing rates of low birth weight (Odds ratio (OR) 1.68 [95% Confidential Interval (CI) 1.19, 2.38]). However, there was no statistically significance difference between non-exposed and exposed groups related to preterm labor (OR 1.98 [95% CI 0.91 to 4.31]; I2 = 68%, p = 0.04). Although, results were inconsistent with primary analysis suggesting a significant association between antenatal stress exposure and the occurrence of higher rates of preterm birth (OR 1.42 [95% CI 1.05 to 1.91]; I2 = 68%, p = 0.04) in the sensitivity analysis. Furthermore, the current review has suggested that stress perceived during antenatal negatively influences fetal life and child development. Yet, further studies are necessary with adequate sample size and longer follow-up time to confirm our findings., Competing Interests: The authors have declared that no competing interests exist.

Objective:  To establish the Pregnancy Sexual Response Inventory (PSRI) scores for each domain before and during pregnancy, and to publish the Brazilian Portuguese version of the PSRI., Methods:  Pregnant women were recruited during antenatal care; the PSRI was administered to 244 women prenatally at Faculdade de Medicina de Botucatu, at Universidade do Estado de São Paulo (UNESP, in the Portuguese acronym). The PSRI scores were estimated based on the Kings Health Questionnaire (KHQ) and the Medical Outcomes Study 36-item short form survey (SF-36). The raw scale type was used to standardize the minimal value and amplitude of each domain. For each domain, the score varied from 0 to 100, and the composite score was obtained as the domain average. The composite score before and during pregnancy was determined by the sum of the scores of all specific domains for each divided by the full domain number. The categorization of the scale into quartiles was established when all PSRI-specific and composite scores were combined., Results:  The composite and specific scores for each domain were categorized into quartiles: 0 < 25 as "very bad;" 25 < 50 as "bad;" 50 < 75 as "good" and 75 to 100 as "excellent." The mean scores were lower during pregnancy than before pregnancy in 8 of the 10 domains. The Brazilian Portuguese PSRI version is presented., Conclusion:  This study allowed the establishment of the PSRI composite and specific scores for each domain, and the categorization of scores into quartiles: very bad, bad, good and excellent. In addition, the Brazilian Portuguese version of the PSRI is presented in full for application in the Brazilian population., Competing Interests: No conflicts of interest have been declared by the authors., (Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.)