The Role of the FGF19 Family in the Pathogenesis of Gestational Diabetes: A Narrative Review.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. Understanding the pathogenesis and appropriate diagnosis of GDM enables the implementation of early interventions during pregnancy that reduce the risk of maternal and fetal complications. At the same time, it provides opportunities to prevent diabetes, metabolic syndrome, and cardiovascular diseases in women with GDM and their offspring in the future. Fibroblast growth factors (FGFs) represent a heterogeneous family of signaling proteins which play a vital role in cell proliferation and differentiation, repair of damaged tissues, wound healing, angiogenesis, and mitogenesis and also affect the regulation of carbohydrate, lipid, and hormone metabolism. Abnormalities in the signaling function of FGFs may lead to numerous pathological conditions, including metabolic diseases. The FGF19 subfamily, also known as atypical FGFs, which includes FGF19, FGF21, and FGF23, is essential in regulating metabolic homeostasis and acts as a hormone while entering the systemic circulation. Many studies have pointed to the involvement of the FGF19 subfamily in the pathogenesis of metabolic diseases, including GDM, although the results are inconclusive. FGF19 and FGF21 are thought to be associated with insulin resistance, an essential element in the pathogenesis of GDM. FGF21 may influence placental metabolism and thus contribute to fetal growth and metabolism regulation. The observed relationship between FGF21 and increased birth weight could suggest a potential role for FGF21 in predicting future metabolic abnormalities in children born to women with GDM. In this group of patients, different mechanisms may contribute to an increased risk of cardiovascular diseases in women in later life, and FGF23 appears to be their promising early predictor. This study aims to present a comprehensive review of the FGF19 subfamily, emphasizing its role in GDM and predicting its long-term metabolic consequences for mothers and their offspring.

Preeclampsia and Obesity-The Preventive Role of Exercise.

Obesity is now recognized as a worldwide epidemic. An inadequate diet and reduced physical activity are acknowledged as the leading causes of excess body weight. Despite growing evidence that obesity is a risk factor for unsuccessful pregnancies, almost half of all women who become pregnant today are overweight or obese. Common complications of pregnancy in this group of women are preeclampsia and gestational hypertension. These conditions are also observed more frequently in women with excessive weight gain during pregnancy. Preeclampsia is one of the most serious pregnancy complications with an unpredictable course, which in its most severe forms, threatens the life and health of the mother and her baby. The early identification of the risk factors for preeclampsia development, including obesity, allows for the implementation of prophylaxis and a reduction in maternal and fetal complications risk. Additionally, preeclampsia and obesity are the recognized risk factors for developing cardiovascular disease in later life, so prophylaxis and treating obesity are paramount for their prevention. Thus, a proper diet and physical activity might play an essential role in the prophylaxis of preeclampsia in this group of women. Limiting weight gain during pregnancy and modifying the metabolic risk factors with regular physical exercise creates favorable metabolic conditions for pregnancy development and benefits the elements of the pathogenetic sequence for preeclampsia development. In addition, it is inexpensive, readily available and, in the absence of contraindications to its performance, safe for the mother and fetus. However, for this form of prevention to be effective, it should be applied early in pregnancy and, for overweight and obese women, proposed as an essential part of planning pregnancy. This paper aims to present the mechanisms of the development of hypertension in pregnancy in obese women and the importance of exercise in its prevention.

Comparative Evaluation of Adipokine Metrics for the Diagnosis of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is one of the most common medical disorders in pregnancy. Adipokines, predominantly secreted by adipose tissue, are involved in numerous metabolic processes. The exact role of adipokines in the pathogenesis of GDM is still not well known, and numerous adipokines have been analysed throughout pregnancy and proposed as biomarkers of GDM. This study aimed to evaluate serum adiponectin, chemerin, lipocalin and apelin levels in GDM and non-GDM women, to assess them as clinically useful biomarkers of the occurrence of GDM and to demonstrate the correlation between the levels of the above adipokines in the blood serum and the increased risk of the development of GDM. The role of these adipokines in the pathogenesis of GDM was also analysed. The statistically significant differences between the levels of adiponectin (7234.6 vs. 9837.5 ng/mL, p < 0.0001), chemerin (264.0 vs. 206.7 ng/mL, p < 0.0001) and lipocalin (39.5 vs. 19.4 ng/mL, p < 0.0001) were observed between pregnant women with GDM and healthy ones. The diagnostic usefulness of the tested adipokines in detecting GDM was also assessed. The research results confirm the hypothesis on the significance of adiponectin, chemerin, lipocalin and apelin in the pathophysiological mechanisms of GDM. We speculate that these adipokines could potentially be established as novel biomarkers for the prediction and early diagnosis of GDM.

The Role of Kisspeptin in the Pathogenesis of Pregnancy Complications: A Narrative Review.

Kisspeptins are the family of neuropeptide products of the KISS-1 gene that exert the biological action by binding with the G-protein coupled receptor 54 (GPR54), also known as the KISS-1 receptor. The kisspeptin level dramatically increases during pregnancy, and the placenta is supposed to be its primary source. The role of kisspeptin has already been widely studied in hypogonadotropic hypogonadism, fertility, puberty disorders, and insulin resistance-related conditions, including type 2 diabetes mellitus, polycystic ovary syndrome, and obesity. Gestational diabetes mellitus (GDM), preeclampsia (PE), preterm birth, fetal growth restriction (FGR), or spontaneous abortion affected 2 to 20% of pregnancies worldwide. Their occurrence is associated with numerous short and long-term consequences for mothers and newborns; hence, novel, non-invasive predictors of their development are intensively investigated. The study aims to present a comprehensive review emphasizing the role of kisspeptin in the most common pregnancy-related disorders and neonatal outcomes. The decreased level of kisspeptin is observed in women with GDM, FGR, and a high risk of spontaneous abortion. Nevertheless, there are still many inconsistencies in kisspeptin concentration in pregnancies with preterm birth or PE. Further research is needed to determine the usefulness of kisspeptin as an early marker of gestational and neonatal complications.

The Polish Society of Gynecologists and Obstetricians Guideline for the diagnostic assessment and management of multiple-gestation pregnancy complicated by fetal growth restriction.

The aim of the Guideline is to unify the diagnostic-therapeutic management of multiple-gestation pregnancies complicated by fetal growth restriction in at least one fetus.

Could Vitamin D Be Effective in Prevention of Preeclampsia?

Prevention of preeclampsia (PE) remains one of the most significant problems in perinatal medicine. Due to the possible unpredictable course of hypertension in pregnancy, primarily PE and the high complication rate for the mother and fetus/newborn, it is urgent to offer pregnant women in high-risk groups effective methods of preventing the PE development or delaying its appearance. In addition, due to the association of PE with an increased risk of developing cardiovascular diseases (CVD) in later life, effective preeclampsia prevention could also be important in reducing their incidence. Ideal PE prophylaxis should target the pathogenetic changes leading to the development of PE and be safe for the mother and fetus, inexpensive and freely available. Currently, the only recognized method of PE prevention recommended by many institutions around the world is the use of a small dose of acetylsalicylic acid in pregnant women with risk factors. Unfortunately, some cases of PE are diagnosed in women without recognized risk factors and in those in whom prophylaxis with acetylsalicylic acid is not adequate. Hence, new drugs which would target pathogenetic elements in the development of preeclampsia are studied. Vitamin D (Vit D) seems to be a promising agent due to its beneficial effect on placental implantation, the immune system, and angiogenic factors. Studies published so far emphasize the relationship of its deficiency with the development of PE, but the data on the benefits of its supplementation to reduce the risk of PE are inconclusive. In the light of current research, the key issue is determining the protective concentration of Vit D in a pregnant woman. The study aims to present the possibility of using Vit D to prevent PE, emphasizing its impact on the pathogenetic elements of preeclampsia development.

Nutrition as Prevention Factor of Gestational Diabetes Mellitus: A Narrative Review.

Gestational diabetes mellitus (GDM) is defined as a glucose tolerance disorder with onset or first recognition during pregnancy. GDM is associated with several adverse maternal and neonatal outcomes. Management to reduce the incidence of GDM could decrease the incidence of these complications. Modification of nutrition in the prevention of GDM is postulated. The vital issue in GDM prevention is the implementation of proper dietary patterns, appropriate physical activity, and a combination of diet and lifestyle modifications. However, intervention studies examining the effects of diet and lifestyle on GDM prevention are contradictory. The aim of this study was to review the scientific evidence on nutritional prevention strategies, including diet and supplementation of some substances such as probiotics, micro/macroelements, fiber, myoinositol, and vitamins that may be effective in reducing the risk of GDM. The presented article is a narrative review. This article indicates that certain nutritional factors may have some benefit in preventing GDM. However, further studies in a variety of populations and large groups of patients are needed. At present, no definitive conclusions can be drawn as to the best intervention in the prevention of GDM.

Thrombocytopenia in pregnant women.

Thrombocytopenia is one of the two most common hematological problems in pregnant women. It is defined as the platelet (PLT) count below 150 × 103/µL. Gestational incidental thrombocytopenia (GIT) represents about 75% of thrombocytopenia cases in pregnancy and it is believed that GIT is secondary to accelerated platelet destruction and increased plasma volume associated with pregnancy. The pregnancy complications such as preeclampsia and its most severe form - HELLP syndrome account for 20% cases of thrombocytopenia in pregnancy and primary immune thrombocytopenic purpura (ITP) - for 3-4 percent. During ITP, maternal antiplatelet antibodies can pass through the placenta and bind to fetal thrombocytes leading to the development of fetal thrombocytopenia which occurs in about 50% cases. Even if the maternal platelet count stabilizes, the estimated fetal and neonatal risk of thrombocytopenia in ITP is approximately 30%. Other types of thrombocytopenia in pregnant women constitute 1-2% of cases (disseminated intravascular coagulation, autoimmunological diseases, congenital, infection and drug-related, concomitant with blood neoplastic diseases). Although thrombocytopenia in pregnant women usually has a mild course, in case of a significant decrease in PLT count may lead to dangerous bleeding, especially when the platelet count falls below 20 × 103/µL. Since it is important to identify the cause of thrombocytopenia and to determine the risk for both the mother and the child, this paper presents the influence of maternal thrombocytopenia on the pregnancy course as well as its etiology and diagnostics. The treatment principles are discussed.

The Potential Role of Chemerin, Lipocalin 2, and Apelin in the Diagnosis and Pathophysiology of Gestational Diabetes Mellitus.

The exact role of adipokines in the pathogenesis of gestational diabetes mellitus (GDM) still remains not fully clear, and multiple studies have analyzed their potential contribution to the pathophysiology of this pregnancy complication. This study is aimed at evaluating serum chemerin, lipocalin 2, and apelin concentrations in GDM and healthy pregnant patients, assessing the correlation between these adipokines, and suggesting the potential role of these cytokines in the diagnosis and pathophysiology of GDM. The study comprised 237 pregnant women: 153 with GDM and 84 with physiological pregnancy. Serum concentrations of chemerin, lipocalin 2, and apelin were obtained at 24-29 weeks of gestation. The mean concentrations of chemerin and lipocalin 2 were significantly higher in the GDM group. The concentration of apelin was slightly higher in the GDM group, but not statistically significant. The strong positive correlation between chemerin and lipocalin 2 concentrations was noticed in both groups. Our data suggest that maternal chemerin and lipocalin 2 may play a significant role in the pathophysiology of GDM. We imply that these adipokines could potentially be established as novel biomarkers for the early identification of GDM. However, more studies are needed to analyze the effect of these adipokines on glucose metabolism during early pregnancy.

Prevention of Hypertensive Disorders of Pregnancy-Is There a Place for Metformin?

The possibility of prophylaxis of hypertensive disorders of pregnancy (HDPs) such as preeclampsia (PE) and pregnancy-induced hypertension is of interest due to the unpredictable course of these diseases and the risks they carry for both mother and fetus. It has been proven that their development is associated with the presence of the placenta, and the processes that initiate it begin at the time of the abnormal invasion of the trophoblast in early pregnancy. The ideal HDP prophylaxis should alleviate the influence of risk factors and, at the same time, promote physiological trophoblast invasion and maintain the physiologic endothelium function without any harm to both mother and fetus. So far, aspirin is the only effective and recommended pharmacological agent for the prevention of HDPs in high-risk groups. Metformin is a hypoglycemic drug with a proven protective effect on the cardiovascular system. Respecting the anti-inflammatory properties of metformin and its favorable impact on the endothelium, it seems to be an interesting option for HDP prophylaxis. The results of previous studies on such use of metformin are ambiguous, although they indicate that in a certain group of pregnant women, it might be effective in preventing hypertensive complications. The aim of this study is to present the possibility of metformin in the prevention of hypertensive disorders of pregnancy with respect to its impact on the pathogenic elements of development.

Ovarian Cancer and Pregnancy-A Current Problem in Perinatal Medicine: A Comprehensive Review.

The frequency of concomitant adnexal tumors in pregnancy is reported to be at 0.15-5.7%, while ovarian cancer complicates 1 in 15,000 to 1 in 32,000 pregnancies, being the second most common gynecologic cancer diagnosed during pregnancy. The aim of this review is to discuss the problem of ovarian cancer complicating pregnancy and the current recommendations for diagnostics and treatment, with an emphasis on the risk to the fetus. A detailed analysis of the literature found in the PubMed and MEDLINE databases using the keywords "ovarian cancer", "ovarian malignancy", "adnexal masses", "ovarian tumor" and "pregnancy" was performed. There were no studies on a large series of pregnant women treated for ovarian malignancies and the management has not been well established. The diagnostics and therapeutic procedures need to be individualized with respect to the histopathology of the tumor, its progression, the gestational age at the time of diagnosis and the mother's decisions regarding pregnancy preservation. The multidisciplinary cooperation of specialists in perinatal medicine, gynecological oncology, chemotherapy, neonatology and psychology seems crucial in order to obtain the best possible maternal and neonatal outcomes.

Adipokines and Endothelium Dysfunction Markers in Pregnant Women with Gestational Hypertension.

OBJECTIVE: The aim of the study was to evaluate the levels of adipokines such as adiponectin and leptin as well as soluble intercellular adhesion molecule-1 (sICAM-1) and endogenous NOS inhibitor-asymmetric dimethylarginine (ADMA), as the endothelium dysfunction markers in pregnant women with gestational hypertension (GH). PATIENTS AND METHODS: Adiponectin, leptin, sICAM-1, and ADMA concentrations were measured in a group of 34 patients with GH and in 32 healthy pregnant women between the 24th and 34th week of gestation with ELISA tests. RESULTS: The patients with GH compared with healthy ones were characterized by significantly higher BMI (28.09 ± 7.90 vs. 22.34 ± 4.21 kg/m2, p=0.016) and higher concentrations of leptin (45.89 ± 35.91 vs. 24.09 ± 24.40 ng/mL, p=0.006). sICAM-1 levels were also higher in the GH group but without the statistical significance (264.51 ± 50.99 vs. 232.56 ± 43.3 ng/ml, p=0.057). There were no significant differences between groups in adiponectin (8.79 ± 8.67 vs. 7.90 ± 3.71 µg/mL, p=0.46, NS) and ADMA (0.57 ± 0.26 vs. 0.60 ± 0.24 µmol/L, p=0.68, NS) levels. The significant correlation between leptin levels and BMI value was observed only in patients with GH (R = 0.56, p=0.02). CONCLUSIONS: The higher levels of leptin in pregnant women with gestational hypertension may be suggestive of the role of leptin in GH development. As the patients in the GH group had higher BMI, hyperleptinemia may link obesity with gestational hypertension. The significance of leptin as the predictive marker of GH development could be implied. It could be postulated that the higher levels of sICAM-1 in the GH patients, although not statistically significant, could reflect some impairment of the endothelium function occurring in GH regardless of BMI. The comparable adiponectin levels in GH and healthy pregnant patients and the lack of its correlation with BMI may indicate the occurrence of a protective mechanism in pregnancy maintaining its concentration and preserving from the consequences of the decrease in its levels in overweight and obese patients. Since ADMA levels were similar in GH and healthy pregnant women, ADMA seems not to be involved in GH pathogenesis, suggesting that NO synthesis is not impaired in this pregnancy complication. As the data on the gestational hypertension pathogenesis and its correlations with adipokines and markers of the endothelium dysfunction are limited, further studies on this issue are warranted.

Aortic dissection during pregnancy - obstetric perspective.

The risk of vascular events during pregnancy is substantially increased. Beyond comparatively frequent vascular diseases, pregnancy may lead also to the development of exceptionally rare vascular events such as the aortic dissection and aortic rupture which are conceivably endangering life conditions. Women with the connective tissue disorders and with a family history of the aorta diseases are especially prone to the aortic complications which may also develop in the absence of these risk factors due to the pregnancy-induced structural changes of the aortic wall. The preconception counselling is vital for patients with aortopathies to assess the risk of the aortic dissection and to establish the most appropriate care plan including the surgical intervention. This review presents the management guidelines in patients with the aortic dissection risk during pregnancy.

FABP4 in Gestational Diabetes-Association between Mothers and Offspring.

Fetuses exposed to gestational diabetes mellitus (GDM) have a higher risk of abnormal glucose homeostasis in later life. The molecular mechanisms of this phenomenon are still not fully understood. Fatty acid binding protein 4 (FABP4) appears to be one of the most probable candidates involved in the pathophysiology of GDM. The main aim of the study was to investigate whether umbilical cord serum FABP4 concentrations are altered in term neonates born to GDM mothers. Two groups of subjects were selected-28 healthy controls and 26 patients with GDM. FABP4, leptin, and ghrelin concentrations in the umbilical cord serum, maternal serum, and maternal urine were determined via an enzyme-linked immunosorbent assay. The umbilical cord serum FABP4 levels were higher in the GDM offspring and were directly associated with the maternal serum FABP4 and leptin levels, as well as the prepregnancy body mass index (BMI) and the BMI at and after delivery; however, they correlated negatively with birth weight and lipid parameters. In the multiple linear regression models, the umbilical cord serum FABP4 concentrations depended positively on the maternal serum FABP4 and negatively on the umbilical cord serum ghrelin levels and the high-density lipoprotein cholesterol. There are many maternal variables that can affect the level of FABP4 in the umbilical cord serum, thus, their evaluation requires further investigation.

Nesfatin-1 and Vaspin as Potential Novel Biomarkers for the Prediction and Early Diagnosis of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is considered to be one of the most frequent medical complication observed among pregnant women. The role of adipokines in the pathogenesis of GDM remains strictly unknown. Different adipokines have been studied throughout gestation, and they have been proposed as biomarkers of GDM and other pregnancy-related complications; however, there is no biomarker reported for GDM screening at present. The aim of this study was to evaluate serum nesfatin-1 and vaspin levels in GDM and non-GDM women, to characterize the correlation between these adipokines, and to assess the potential role of circulating adipokines in the prediction of risk of gestational diabetes mellitus. Serum concentrations of nesfatin-1 and vaspin were measured in 153 women with GDM, and in 84 patients with uncomplicated pregnancy by enzyme-linked immunosorbent assay (ELISA) kits, according to the manufacturer's instructions. Circulating levels of nesfatin-1 and vaspin were significantly lower in the GDM group than in the control group. Nesfatin-1 levels were negatively correlated with vaspin levels. The results of this study point out the possible role of nesfatin-1 and vaspin as potential novel biomarkers for the prediction and early diagnosis of GDM. Further studies are necessary to evaluate the influence of nesfatin-1 and vaspin on glucose metabolism in the early stages of GDM.

Adiponectin and Omentin Levels as Predictive Biomarkers of Preterm Birth in Patients with Gestational Diabetes Mellitus.

OBJECTIVE: The aim of this study was to determine any changes in adiponectin and omentin levels in GDM patients who delivered at term and preterm and to evaluate whether adipokines can be useful as a clinical biomarker to predict subsequent preterm delivery. PATIENTS AND METHODS: The levels of adiponectin and omentin were measured in four groups: (1) women with GDM who delivered at term (n=63); (2) women with GDM who had the symptoms of threatened preterm labor and delivered at term (n=23); (3) women with GDM and spontaneous preterm birth (before 37 completed weeks of gestation) (n=19); (4) women with physiological pregnancy (n=55). RESULTS: In comparison with control group the median adiponectin concentrations were significantly lower in all GDM groups (10737 versus 8879; 7057; 6253 ng/ml, respectively; p<0.01). The median omentin concentrations were also significantly lower in all GDM groups in comparison with control group (469 versus 432; 357; 308 ng/ml, respectively; p<0.01). No significant differences in adiponectin and omentin levels between the GDM, preterm labor, and preterm birth groups were observed. However, there was a trend towards lower adiponectin and omentin levels in preterm birth group. The strong correlations between adiponectin and omentin levels were observed in all groups (R=0.801, p<0.001; R=0.824, p<0.001; R=0.705, p<0.001; R=0.764, respectively; p<0.001). In the univariable logistic regression model, significant correlation between omentin concentrations and preterm birth occurrence was found. CONCLUSIONS: Our findings suggest that omentin-1, rather than adiponectin, could be useful as a predictor of preterm birth in patients with gestational diabetes mellitus.