Substance P Concentration in Gestational Diabetes and Excessive Gestational Weight Gain and Its Impact on Neonatal Anthropometry.

Fetal programming is a process initiated by intrauterine conditions, leaving a lasting impact on the offspring's health, whether they manifest immediately or later in life. It is believed that children born to mothers with gestational diabetes mellitus (GDM) and excessive gestational weight gain (EGWG) may be at an increased risk of developing type 2 diabetes mellitus (T2DM) and obesity later in their adult lives. Substance P is a neurotransmitter associated with obesity development and impairment of insulin signaling. Dysregulation of substance P could lead to several pregnancy pathologies, such as preeclampsia and preterm birth. Our study aimed to compare substance P concentrations in serum and umbilical cord blood in patients with GDM, EGWG, and healthy women with a family history of gestational weight gain. Substance P levels in umbilical cord blood were significantly higher in the GDM group compared to the EGWG and control groups. Substance P levels in serum and umbilical cord blood were positively correlated in all groups and the GDM group. A very interesting direction for future research is the relationship between the concentration of substance P in newborns of diabetic mothers and the occurrence of respiratory distress syndrome as a complication of impaired surfactant synthesis. To our knowledge, it is the first study assessing substance P concentration in GDM and EGWG patients.

Recent Insights and Recommendations for Preventing Excessive Gestational Weight Gain.

Recommendations for weight gain during pregnancy are based on pre-pregnancy body mass index (BMI). Pregnancy is a risk factor for excessive weight gain and many endocrine problems, making it difficult to return to pre-pregnancy weight and increasing the risk of postpartum obesity and, consequently, type 2 diabetes and metabolic syndrome. Both excessive gestational weight gain (EGWG) and obesity are associated with an increased risk of gestational hypertension, pre-eclampsia, gestational diabetes, cesarean section, shoulder dystocia, and neonatal macrosomia. In the long term, EGWG is associated with increased morbidity and mortality, particularly from diabetes, cardiovascular disorders, and some cancers. This study aims to present recommendations from various societies regarding weight gain during pregnancy, dietary guidance, and physical activity. In addition, we discuss the pathophysiology of this complication and the differential diagnosis in pregnant women with EGWG. According to our research, inadequate nutrition might contribute more significantly to the development of EGWG than insufficient physical activity levels in pregnant women. Telehealth systems seem to be a promising direction for future EGWG prevention by motivating women to exercise. Although the importance of adequate pre-pregnancy weight and weight gain during pregnancy is well known, an increasing number of women gain excessive weight during pregnancy.

Association of DPP-4 Concentrations with the Occurrence of Gestational Diabetes Mellitus and Excessive Gestational Weight Gain.

Gestational diabetes mellitus (GDM) is considered one of the most common diseases that occur during pregnancy. In addition to increasing the risk of numerous complications throughout gestation, it is also believed to have a long-term potential to impact the risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular disease for the mother and her offspring. While there are clear guidelines for healthy weight gain in pregnancy depending on pre-pregnancy BMI, as well as dietary and training recommendations to achieve this, an increasing number of women are experiencing excessive gestational weight gain (EGWG). Such patients have a higher risk of developing GDM and gestational hypertension, as well as requiring caesarian delivery. Dipeptidyl peptidase-4 (DPP-4) is a glycoprotein that seems to play an important role in glucose metabolism, and inhibition of its activity positively affects glucose regulation. The aim of our study was to compare DPP-4 concentrations in patients with GDM and EGWG with healthy women. DPP-4 levels were assessed in serum and urine samples collected on the day of delivery. The bioelectrical impedance analysis (BIA) method was also used to analyze the body composition of patients on the second day of the postpartum period. DPP-4 serum concentrations were significantly higher in patients in the GDM and EGWG groups compared to healthy women. Urinary DPP-4 concentrations were significantly higher in the control and GDM groups than in the EGWG group. Serum DPP-4 levels were positively correlated with BMI measured before pregnancy, on the delivery day, and in the early postpartum period, among other factors. According to our knowledge, this is the first study to determine DPP-4 levels in EGWG patients. DPP-4 may be related to the occurrence of GDM and EGWG; however, this requires further research.

Influence of Breastfeeding on the State of Meta-Inflammation in Obesity-A Narrative Review.

Obesity has become an emerging health issue worldwide that continues to grow in females of reproductive age as well. Obesity, as a multisystem and chronic disease, is associated with metabolic inflammation, which is defined as chronic low-grade systemic inflammation mediated by, i.a., adipose tissue macrophages. Lactation has been proven to have a beneficial influence on maternal health and could help restore metabolic balance, especially in the state of maternal obesity. In this review, we aimed to analyze the influence of breastfeeding on chronic low-grade meta-inflammation caused by obesity. We performed a comprehensive literature review using the PubMed, Science Direct, and Google Scholar electronic databases. For this purpose, we searched for "metabolic inflammation"; "meta-inflammation"; "obesity"; "breastfeeding"; "fetal programming"; "energy metabolism"; "postpartum"; "immunity"; "immune system"; and "inflammation" keyword combinations. While the clinical impact of breastfeeding on maternal and offspring health is currently well known, we decided to gain insight into more specific metabolic effects of adiposity, lipid, and glucose homeostasis, and immunological effects caused by the activity of cytokines, macrophages, and other immune system cells. Further research on the immunological and metabolic effects of breastfeeding in obese patients is key to understanding and potentially developing obesity therapeutic strategies.

Stress of Prematurity in the Experience of the COVID-19 Pandemic-Current State of Knowledge.

Stress is a process that triggers various physiological, hormonal and psychological mechanisms in response to a threat, which significantly affects the health of an individual. The COVID-19 pandemic introduced a lot of social changes that required constant adaptation to unfavorable conditions. The aim of the study was to assess the impact of stress related to this pandemic on pregnant women, mothers of premature infants and their families, and on obstetric complications, particularly preterm birth. A comprehensive literature review was performed using electronic databases such as Pubmed, Science Direct and Google Scholar. Keywords such as: "prematurity"; "pregnancy"; "stress"; "COVID-19" and various combinations of the above were used. Maternal stress and anxiety increase the levels of corticotropin-releasing hormone (CRH) in the placenta, which in turn affects the incidence of preterm birth and many other related maternal and neonatal complications. In addition, it was found that SARS-CoV-2 infection may increase the risk of this phenomenon. The COVID-19 pandemic has adversely affected preterm birth rates and the mental health of mothers of preterm infants, exacerbating their negative experience of having a premature baby. More research is needed to demonstrate the long-term effects of COVID-19 stress on prematurity.

Impact of Obesity and Diabetes in Pregnant Women on Their Immunity and Vaccination.

Pregnant women with obesity and diabetes are at increased risk of developing infections and other complications during pregnancy. Several mechanisms are involved in the immunological mechanisms that contribute to reduced immunity in these populations. Both obesity and diabetes are associated with chronic low-grade inflammation that can lead to an overactive immune response. Pregnant women with obesity and diabetes often have an increase in pro-inflammatory cytokines and adipokines, such as TNF-α, IL-6, IL-1ß, leptin, and resistin, which are involved in the inflammatory response. Insulin resistance can also affect the functioning of immune cells. Furthermore, both conditions alter the composition of the gut microbiome, which produces a variety of biomolecules, including short-chain fatty acids, lipopolysaccharides, and other metabolites. These substances may contribute to immune dysfunction. In addition to increasing the risk of infections, obesity and diabetes can also affect the efficacy of vaccinations in pregnant women. Pregnant women with obesity and diabetes are at increased risk of developing severe illness and complications from COVID-19, but COVID-19 vaccination may help protect them and their fetuses from infection and its associated risks. Since both obesity and diabetes classify a pregnancy as high risk, it is important to elucidate the impact of these diseases on immunity and vaccination during pregnancy. Research examining the efficacy of the COVID-19 vaccine in a high-risk pregnant population should be of particular value to obstetricians whose patients are hesitant to vaccinate during pregnancy. Further research is needed to better understand these mechanisms and to develop effective interventions to improve immune function in these populations.

Biomolecules Involved in Both Metastasis and Placenta Accreta Spectrum-Does the Common Pathophysiological Pathway Exist?

The process of epithelial-to-mesenchymal transition (EMT) is crucial in the implantation of the blastocyst and subsequent placental development. The trophoblast, consisting of villous and extravillous zones, plays different roles in these processes. Pathological states, such as placenta accreta spectrum (PAS), can arise due to dysfunction of the trophoblast or defective decidualization, leading to maternal and fetal morbidity and mortality. Studies have drawn parallels between placentation and carcinogenesis, with both processes involving EMT and the establishment of a microenvironment that facilitates invasion and infiltration. This article presents a review of molecular biomarkers involved in both the microenvironment of tumors and placental cells, including placental growth factor (PlGF), vascular endothelial growth factor (VEGF), E-cadherin (CDH1), laminin γ2 (LAMC2), the zinc finger E-box-binding homeobox (ZEB) proteins, αVß3 integrin, transforming growth factor ß (TGF-ß), ß-catenin, cofilin-1 (CFL-1), and interleukin-35 (IL-35). Understanding the similarities and differences in these processes may provide insights into the development of therapeutic options for both PAS and metastatic cancer.

Do Serum Galectin-9 Levels in Women with Gestational Diabetes and Healthy Ones Differ before or after Delivery? A Pilot Study.

Gestational diabetes mellitus (GDM) is a common metabolic disease that occurs during pregnancy, with the placenta playing an important role in its pathophysiology. Currently, the role of galectin-9 in the development of GDM is unknown. The aim of this study was to compare galectin-9 concentrations in healthy pregnant women and those with GDM. Galectin-9 levels were assessed in serum samples taken both just before and after delivery, as well as in urine samples collected in the postpartum period. Maternal body composition and hydration status were evaluated using the bioelectrical impedance analysis (BIA) method. There were no statistically significant differences in the concentration of galectin-9 in women with GDM compared to healthy pregnant women in their serum samples taken just before delivery, nor in their serum and urine samples collected in the early postpartum period. However, serum galectin-9 concentrations taken before delivery were positively correlated with BMI and parameters related to the amount of adipose tissue assessed in the early postpartum period. Additionally, there was a correlation between serum galectin-9 concentrations taken before and after delivery. Galectin-9 is unlikely to become a diagnostic marker for GDM. However, this subject requires further clinical research in larger groups.

Leptin/SFRP5 ratio as a potential predictor of postpartum weight retention. A prospective pilot study.

Excessive gestational weight gain (EGWG) and failure to lose weight within 6 months from delivery are important and identifiable predictors of the long-term obesity. The aim of the study was to verify clinical usefulness of several substances that had been proved to play a significant role in metabolism and body mass regulation, i.e., leptin, ghrelin, fatty acid binding protein 4 (FABP4), secreted frizzled-related protein 5 (SFRP5), and vaspin, in relation to certain laboratory results, body composition and hydration status of females in the early postpartum period. The main goal was to determine a potential marker, which assessed as early as 48 hours after delivery, could predict serious difficulties in achieving pre pregnancy body mass of women with EGWG six months afterwards. The same inclusion criteria applied to the study group (women with EGWG) as well as the control group (women with appropriate body mass gain in pregnancy). These included normal pre-pregnancy BMI, absence of any diseases prior, during pregnancy and after delivery, 6-month long breastfeeding. Postpartum weight retention (PPWR) depended positively on gestational weight gain as well as the leptin/SFRP5 ratio assessed 48 hours after delivery. Both obstetricians and midwives should pay special attention to proper nutrition of pregnant women. The assessment of biophysical and biochemical parameters in the early postpartum period, when the mothers are usually hospitalized, seems to allow to predict the risk of greater body weight retention. Future research will help to determine to what extent the circulating concentrations of leptin and SFRP5 in the early puerperium are important for prediction of maternal PPWR and obesity.

Bile Acids in Intrahepatic Cholestasis of Pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is the most common, reversible, and closely related to pregnancy condition characterized by elevated levels of bile acids (BAs) in blood serum and an increased risk of adverse perinatal outcomes. Due to the complex interactions between the mother and the fetus in metabolism and transplacental BAs transport, ICP is classified as a fetal-maternal disease. The disease is usually mild in pregnant women, but it can be fatal to the fetus, leading to numerous complications, including intrauterine death. The pathophysiology of the disease is based on inflammatory mechanisms caused by elevated BA levels. Although ICP cannot be completely prevented, its early diagnosis and prompt management significantly reduce the risk of fetal complications, the most serious of which is unexpected intrauterine death. It is worth emphasizing that all diagnostics and management of ICP during pregnancy are based on BA levels. Therefore, it is important to standardize the criteria for diagnosis, as well as recommendations for management depending on the level of BAs, which undoubtedly determines the impact on the fetus. The purpose of this review is to present the potential and importance of BAs in the detection and rules of medical procedure in ICP.

Incretins as a Potential Treatment Option for Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a metabolic disease affecting an increasing number of pregnant women around the world. It is not only associated with numerous perinatal complications but also has long-term consequences impacting maternal health and fetal development. To prevent them, it is important to keep glucose levels under control. As much as 15-30% of GDM patients will require treatment with insulin, metformin, or glyburide. With that in mind, it is crucial to keep searching for novel and improved pharmacotherapies. Nowadays, there are ongoing studies investigating the use of other groups of drugs that have proven successful in the treatment of T2DM. Glucagon-like peptide-1 (GLP-1) receptor agonist and dipeptidyl peptidase-4 (DPP-4) inhibitor are among the drugs targeting the incretin system and are currently receiving significant attention. The aim of our review is to demonstrate the potential of these medications in treating GDM and preventing its later complications. It seems that both groups may be successful in the GDM management used alone or as an addition to better-known drugs, including metformin and glyburide. However, more clinical trials are needed to confirm their importance in GDM treatment and to demonstrate effective therapeutic strategies.

Changes in the Gut Microbiome and Pathologies in Pregnancy.

Pregnancy is a special period in a woman's life when her organism undergoes multiple physiological changes so that the fetus has optimal conditions for growth and development. These include modifications in the composition of the microbiome that occur between the first and third trimesters of pregnancy. There is an increase in Akkermansia, Bifidobacterium, and Firmicutes, which have been associated with an increase in the need for energy storage. The growth in Proteobacteria and Actinobacteria levels has a protective effect on both the mother and the fetus via proinflammatory mechanisms. The aim of the study is to review the research on the relationship between the mother's intestinal microbiome and gestational pathologies. Changes in the maternal gut microbiome is probably one of the mechanisms that occurs in various pregnancy diseases such as preeclampsia, fetal growth restriction, gestational diabetes mellitus, excessive gestational weight gain, and premature birth. For this reason, it seems vital to pay attention to certain interventions that can benefit the affected patients both in the short term, by preventing complications during pregnancy, and in the long term, as one of the mechanisms occurring in various gestational diseases is dysbiosis of the maternal intestinal flora.

Effects of Probiotic Supplementation during Pregnancy on the Future Maternal Risk of Metabolic Syndrome.

Probiotics are live microorganisms that induce health benefits in the host. Taking probiotics is generally safe and well tolerated by pregnant women and their children. Consumption of probiotics can result in both prophylactic and therapeutic effects. In healthy adult humans, the gut microbiome is stable at the level of the dominant taxa: Bacteroidetes, Firmicutes and Actinobacteria, and has a higher presence of Verrucomicrobia. During pregnancy, an increase in the number of Proteobacteria and Actinobacteria phyla and a decrease in the beneficial species Roseburia intestinalis and Faecalibacterium prausnitzii are observed. Pregnancy is a "window" to the mother's future health. The aim of this paper is to review studies assessing the potentially beneficial effects of probiotics in preventing the development of diseases that appear during pregnancy, which are currently considered as risk factors for the development of metabolic syndrome, and consequently, reducing the risk of developing maternal metabolic syndrome in the future. The use of probiotics in gestational diabetes mellitus, preeclampsia and excessive gestational weight gain is reviewed. Probiotics are a relatively new intervention that can prevent the development of these disorders during pregnancy, and thus, would reduce the risk of metabolic syndrome resulting from these disorders in the mother's future.

Novel Biomolecules in the Pathogenesis of Gestational Diabetes Mellitus 2.0.

Gestational diabetes mellitus (GDM) has become a major public health problem and one of the most discussed issues in modern obstetrics. GDM is associated with serious adverse perinatal outcomes and long-term health consequences for both the mother and child. Currently, the importance and purposefulness of finding a biopredictor that will enable the identification of women with an increased risk of developing GDM as early as the beginning of pregnancy are highly emphasized. Both "older" molecules, such as adiponectin and leptin, and "newer" adipokines, including fatty acid-binding protein 4 (FABP4), have proven to be of pathophysiological importance in GDM. Therefore, in our previous review, we presented 13 novel biomolecules, i.e., galectins, growth differentiation factor-15, chemerin, omentin-1, osteocalcin, resistin, visfatin, vaspin, irisin, apelin, FABP4, fibroblast growth factor 21, and lipocalin-2. The purpose of this review is to present the potential and importance of another nine lesser known molecules in the pathogenesis of GDM, i.e., 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), angiopoietin-like protein-8 (ANGPTL-8), nesfatin-1, afamin, adropin, fetuin-A, zonulin, secreted frizzled-related proteins (SFRPs), and amylin. It seems that two of them, fetuin-A and zonulin in high serum levels, may be applied as biopredictors of GDM.

Metformin as a Potential Treatment Option for Endometriosis.

Endometriosis is a common disease in women of reproductive age, and its pathogenesis seems to be largely affected by hormone imbalance, inflammation, oxidative stress, and autophagy dysregulation. These pathophysiological disturbances interact with one another through mechanisms that are still awaiting elucidation. The aim of this article is to present current knowledge regarding the possibilities of using metformin in the pharmacological treatment of endometriosis. Metformin is an insulin sensitizer widely used for the treatment of type 2 diabetes mellitus. The pleiotropic effects of metformin are mainly exerted through the activation of AMP-activated protein kinase, which is the key cellular energy homeostasis regulator that inhibits mTOR, a major autophagy suppressor. Metformin regresses endometriotic implants by increasing the activity of superoxide dismutase. It is also an inhibitor of metalloproteinase-2, decreasing the levels of the vascular endothelial growth factor and matrix metalloproteinase-9 in animal studies. In endometriosis, metformin might modify the stroma-epithelium communication via Wnt2/ß-catenin. With its unique therapeutic mechanisms and no serious side effects, metformin seems to be a helpful anti-inflammatory and anti-proliferative agent in the treatment of endometriosis. It could be a missing link for the successful treatment of this chronic disease.

Novel Biomolecules in the Pathogenesis of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is one of the most common metabolic diseases in pregnant women. Its early diagnosis seems to have a significant impact on the developing fetus, the course of delivery, and the neonatal period. It may also affect the later stages of child development and subsequent complications in the mother. Therefore, the crux of the matter is to find a biopredictor capable of singling out women at risk of developing GDM as early as the very start of pregnancy. Apart from the well-known molecules with a proven and clear-cut role in the pathogenesis of GDM, e.g., adiponectin and leptin, a potential role of newer biomolecules is also emphasized. Less popular and less known factors with different mechanisms of action include: galectins, growth differentiation factor-15, chemerin, omentin-1, osteocalcin, resistin, visfatin, vaspin, irisin, apelin, fatty acid-binding protein 4 (FABP4), fibroblast growth factor 21, and lipocalin-2. The aim of this review is to present the potential and significance of these 13 less known biomolecules in the pathogenesis of GDM. It seems that high levels of FABP4, low levels of irisin, and high levels of under-carboxylated osteocalcin in the serum of pregnant women can be used as predictive markers in the diagnosis of GDM. Hopefully, future clinical trials will be able to determine which biomolecules have the most potential to predict GDM.

Cytokine Storms in the Course of COVID-19 and Haemophagocytic Lymphohistiocytosis in Pregnant and Postpartum Women.

The term 'cytokine storm' (CS) applies to a pathological autoimmune reaction when the interactions that lead to cytokine production are destabilised and may even lead to death. CS may be induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we present our analysis of certain pathological processes that induce a CS in pregnant and postpartum women. We draw our attention to the similarities between the severe course of Coronavirus Disease 2019 (COVID-19) and haemophagocytic lymphohistiocytosis (HLH). It is noteworthy that many of the criteria used to diagnose HLH are described as COVID-19 mortality predictors. Cytokine storms are considered to be an important cause of death in patients with the severe course of SARS-CoV-2 infection. Due to the fact that pregnant women are in an immunosuppressive state, viral pulmonary infections are more perilous for them-possible risks include miscarriage, intrauterine growth restriction or birth before the term; sometimes ventilation support is needed. HLH should be considered in pregnant and puerperal women suffering from moderately severe to severe COVID-19 and presenting with: fever unresponsive to antibiotic therapy, cytopenia, hepatitis and hyperferritinaemia. The HLH disorder is rare and difficult to diagnose; however, its early detection could reduce patient mortality.

The Possibility of Using Bioelectrical Impedance Analysis in Pregnant and Postpartum Women.

Pregnancy is a time of significant changes occurring in the composition of a woman's body in order to provide support for the growth and development of the foetus. Bioelectrical impedance analysis (BIA) is used to assess the body composition and hydration status. This technique represents a non-invasive, reliable, and fast clinical approach, which is well tolerated by patients. A segmental impedance measurement might be advantageous in pregnant women, particularly in late pregnancy. The purpose of this paper is to provide a review of different applications of BIA in pregnant and postpartum women. It seems that BIA has a better prognostic potential for gestational and post-partum outcomes than body mass index. The BIA method can be successfully used to study the effect of excessive gestational weight gain in pregnancy on the development of obstetric complications. Studying the mother's body composition and correlating it with her energy balance could facilitate the development of dietary recommendations for women. Evaluation of the body composition can provide important clues for diagnosis of gestational diabetes mellitus in pregnant women with a low risk of this disease. BIA is also used as one of the additional tests in assessing the risk of developing gestational hypertension and preeclampsia.

The Potential of Non-Invasive Biomarkers for Early Diagnosis of Asymptomatic Patients with Endometriosis.

Endometriosis is a disease that affects women of reproductive age and has a significantly negative impact on their well-being. The main symptoms are dysmenorrhoea, chronic pelvic pain and infertility. In many patients the diagnostic process is very long and can take up to 8-12 years. Laparoscopy, an invasive method, is still necessary to confirm the diagnosis. Therefore, development of more effective diagnostic markers appears to be of the utmost importance for early diagnosis of endometriosis and provision of appropriate treatment. From a clinical point of view, detection of early-stage endometriosis in asymptomatic patients is an ideal situation since early diagnosis of endometriosis may delay the onset of symptoms as well as prevent progression and complications. In the meantime, Cancer Antigen 125 (CA-125) is still the most frequently studied and used marker. Other glycoproteins, growth factors and immune markers seem to play an important role. However, the search for an ideal endometriosis marker is still underway. Further studies into the pathogenesis of endometriosis will help to identify biomarkers or sets of biomarkers with the potential to improve and speed up the diagnostic process in a non-invasive way.

Preeclampsia and Cardiovascular Risk for Offspring.

There is growing evidence of long-term cardiovascular sequelae in children after in utero exposure to preeclampsia. Maternal hypertension and/or placental ischaemia during pregnancy increase the risk of hypertension, stroke, diabetes, and cardiovascular disease (CVD) in the offspring later in life. The mechanisms associated with CVD seem to be a combination of genetic, molecular, and environmental factors which can be defined as fetal and postnatal programming. The aim of this paper is to discuss the relationship between pregnancy complicated by preeclampsia and possibility of CVD in the offspring. Unfortunately, due to its multifactorial nature, a clear dependency mechanism between preeclampsia and CVD is difficult to establish.