Elżbieta Poniedziałek-Czajkowska

Glucocorticoids in Pregnancy

The fetus may be exposed to increased endogenous or synthetic glucocorticoid (GS) exposure in late gestation. Approximately 7% of pregnant women in Europe and North America are treated with synthetic GSs to promote lung maturation in fetuses at risk of preterm delivery. Maternal steroid treatment before preterm delivery is one of the best documented and most cost effective life saving treatments in prenatal medicine but, in certain circumstances, the price of accelerated lung maturity may be loss of brain cells, increased neurodevelopmental disability, intra-uterine growth restriction (IUGR), and an increased risk of preterm delivery, of programming of post-natal hypertension, and of increased post-natal activity in the hypothalamo-pituitary-adrenal (HPA) axis. Placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is the key enzyme which protects the fetus from overexposure to GSs by their oxidation into inactive derivates. We review the evidence for the metabolism of GSs during pregnancy and how endogenous and synthetic GSs cause other changes in the placenta which affect fetal development.

Nitric Oxide in Normal and Preeclamptic Pregnancy

Nitric oxide (NO) is a key molecule involved in a variety of biological functions throughout the whole body. Many studies have been devoted to establish the role of NO in perinatal medicine and the different findings have promoted the clinical use of NO donors as new pharmacological tools. NO regulates the vascular tone and blood flow by activating soluble guanylate cyclase in the vascular smooth muscles. NO is essential for leukocyte adhesion and platelet aggregation, and it controls mitochondrial oxygen consumption. Abnormalities in vascular NO production and transport result in endothelial dysfunction with various cardiovascular disorders such as hypertension, atherosclerosis and angiogenesis-associated disorders. The NO system has important roles in mammalian reproductive physiology, especially in the utero-placental system. It has been shown to participate in the extravillous trophoblast invasion of decidua and myometrium, in regulation of vascular reactivity of utero-placental and fetal-placental circulations, in prevention of platelet and neutrophil aggregation and adhesion in the intervillous space, and in trophoblast apoptosis. The aim of this review is to present the theoretical background and significance of NO in normal and preeclamptic pregnancy as well as to consider how NO donors could be useful in clinical practice.

Fetal Blood Saturation during the 1st and 2nd Stage of Labor and Its Relation to the Neonatal Outcome

Objective: The aim of this study was to evaluate fetal blood oxygenation (SpO₂) by means of continuous pulse oximetry during labor and its relation to the neonatal outcome. Materials and Methods: Fetal SpO₂ was measured continuously during labor with a noninvasive pulse oximetry for fetal application. The average, minimum and maximum SpO₂ levels were evaluated separately for the 1st and 2nd stage of labor. The average SpO₂ of the fetus was compared to the neonatal outcome assessed by the levels of pH, pO₂ and pCO₂ in the fetus’ umbilical blood and to the Apgar score. Results: Twenty-eight patients were monitored by fetal pulse oximetry. All the patients had normal, vaginal delivery. During the 1st stage of labor, the average fetal SpO₂ was 51.78 ± 8.00%, the minimum SpO₂ level was 37.61 ± 9.86%, and the maximum level of SpO₂ was 63.82 ± 7.37%; in the 2nd stage of labor, the average SpO₂ level was 44.91 ± 8.28%, the minimum level was 35.00 ± 9.22%, and the maximum SpO₂ was 52.30 ± 9.36%. A significant decrease in the fetal average and maximum SpO₂ levels was observed between the 1st and the 2nd stages of labor (the average SpO₂ was 51.78 ± 8.00% vs. 44.91 ± 8.28%, p = 0.00029; the maximum SpO₂ was 63.82 ± 7.37% vs. 52.30 ± 9.36%, p < 0.00001). A significant correlation between the average SpO₂ level during the 1st and 2nd stage of labor and the Apgar score at the first minute of outcome was observed (R = 0.43, p = 0.031). No relationship between the fetal SpO₂ during the 1st and the 2nd stage of labor and the pH, pCO₂, and pO₂ in the fetal umbilical blood were observed. Conclusions: During the 2nd stage of labor, a significant decrease in the fetus’ SpO₂ can be observed. The fetus’ SpO₂ level >30% in the 1st and 2nd stage of labor was related to the good neonatal outcome. The assessment of the fetal SpO₂ during the 1st stage of labor seems to be important in predicting neonatal outcome.

Polyunsaturated Fatty Acids in Pregnancy and Metabolic Syndrome: A Review

This review presents available evidence for possible application of n-3 long chain polyunsaturated fatty acids (PUFAs) in pregnant obese women with metabolic syndrome (MS) and focuses on prophylaxis of pregnancy complications associated with MS such as gestational hypertension, preeclampsia and gestational diabetes. Dietary supplementation with n-3 PUFAs has recently become popular and their adequate intake during pregnancy and early childhood is of clinical importance. The results of experimental and epidemiological investigations reveal that n-3 PUFAs, especially α- linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), may decrease the risk of cardiovascular diseases. It is believed that n-3 PUFAs affect a multitude of molecular pathways, involving regulation of gene expression, alteration of physical and chemical properties of cellular membranes and modulation of membrane channels and proteins. A large body of evidence focuses on anti-inflammatory properties of PUFAs which seem to be fundamental in prevention and reversing of insulin resistance, atherogenic dyslipidemia, hypertension, thromboembolism and in improving vascular function. Despite the potential PUFAs benefits of decreasing insulin resistance, their application in order to prevent preeclampsia, gestational hypertension and gestational diabetes mellitus in pregnant women with MS has not yet been established. Numerous reports have revealed that appropriate fetal development, including neuronal, retinal and immune function depends on EPA and DHA which are crucial also for prevention of preterm birth. Thus the supplementation with EPA and DHA is highly recommended during pregnancy although the optimal dosing and treatment strategies still need to be determined.

Anticoagulant Therapy in Pregnant Patients with Metabolic Syndrome: A Review

Pregnancy is a specific state of heightened coagulability related to the increase in procoagulant agents and to the reduced fibrinolysis. Pregnancy is associated with a 4-fold increased risk of developing venous thromboembolism (VTE) and this risk still increases to 14-fold during puerperium. A correlation between the metabolic syndrome and development of cardiovascular events and cerebrovascular incidents has been described. Such a relationship is referred to a hypercoagulable state due to increased serum levels of the plasminogen activator inhibitor-1 (PAI-1), fibrinogen, factor (F) VII and VIII, von Willebrand factor and from endothelial activation, caused by increased circulating adhesion molecules. As to the risk of VTE, the probability for its association with cardiovascular incidents is increased by common underlying mechanisms such as the activation of platelets and the blood coagulation. A correlation between idiopathic VTE and the metabolic syndrome has been reported. The anticoagulant therapy may be recommended during the pregnancy for the treatment or the prophylaxis of VTE and, in women with artificial heart valves, for the prevention of the valve thrombosis and systemic embolisation. There are also specific conditions during pregnancy which benefit from anticoagulant use, such as recurrent fetal loss, thrombophilia and assisted reproductive technology. There are no published specific data about using of anticoagulant agents in pregnant patients with the metabolic syndrome except for a few articles addressing reproductive problems. The mechanisms of anticoagulant action were studied with the focus on heparinoids, because of their safety not only for the patient but also for the fetus. The new oral anticoagulants were also shortly described although they have been contraindicated during the pregnancy.

Intercellular Adhesion Molecule and Endogenous NOS Inhibitor: Asymmetric Dimethylarginine in Pregnant Women with Gestational Diabetes Mellitus

Objective. The aim of the study was to evaluate the concentrations of soluble intercellular adhesion molecule-1 (s-ICAM-1) and endogenous NOS inhibitor, asymmetric dimethylarginine (ADMA), as markers of endothelium dysfunction in patients with gestational diabetes mellitus (GDM). Patients and Methods. The levels of s-ICAM-1 and ADMA were analysed in the group of 56 patients with GDM and compared to 25 healthy pregnant women. The concentrations of s-ICAM-1 and ADMA were measured in serum using ELISA tests. Results. The groups did not differ by baseline descriptors: age (30.75 ± 6.32 versus 28.50 ± 4.95 years, NS) and gestational age (28.96 ± 2.85 versus 29.12 ± 2.96 hbd, NS). The patients with GDM were more obese (BMI 27.93 ± 7.02 versus 22.34 ± 4.21 kg/m2, p = 0.032) and had higher concentration of C-reactive protein (6.46 ± 6.03 versus 3.18 ± 3.83 mg/L, p = 0.029). In the GDM group the level of ADMA was lower (0.38 ± 0.17 versus 0.60 ± 0.28 μmol/L, p = 0.001) and the level of s-ICAM-1 was significantly higher (289.95 ± 118.12 versus 232.56 ± 43.31 ng/mL, p = 0.036) compared to controls. Conclusions. The pregnant women with GDM are characterized by higher concentration of s-ICAM-1 that reflects the activation and dysfunction of the endothelial cells. The decreased ADMA level in GDM patients seems to be preventive in the limitation of NO synthesis caused by the impaired insulin action and the endothelial dysfunction.

The role of new adipokines in gestational diabetes mellitus pathogenesis

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition dur-ing pregnancy. Explanation of the GDM pathogenesis is important due to preventing gestational complications. During pregnancy there are significant changes in maternal metabolism. Many of these changes are influenced by different adi-pokines produced in the placenta and adipose tissue. The exact role of adipokines in the pathogenesis of GDM remains still unknown. Several adipokines have been analysed throughout gestation and their levels have been suggested as biomarkers of maternal-perinatal outcomes. Some of them have been postulated as significant in the pathogenesis of pregnancy complications like GDM. This report aims to review some of the recent topics of adipokine research that may be of particular importance in patho-physiology and diagnosis of gestational diabetes mellitus. Because of manuscript length limitations, after thorough literature review and in view of the recent evidence, we focus on the one of the most well-known adipokine: adiponectin, and not so well-studied: nesfatin-1, chemerin, ghrelin, and CTRP 1.

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.