To evaluate a level of expression of endoglin (Eng), leptin (Lep), placental growth factor (PlGF), and hypoxia-inducible factor-1alpha (HIF-1α) in placenta among women with pre-eclampsia and diabet...

AIM: The aim of this study was to compare placental morphological features from women with different types of diabetes mellitus considering method of DM correction. MATERIALS AND METHODS: A retrospective, single-center, cohort study was carried out. We analyzed morphological examination results of 3300 placentas, which made uр the following comparison groups: type 1 diabetes mellitus on continuous subcutaneous insulin infusion (n = 60), type 1 diabetes mellitus on multiple subcutaneous insulin injections (n = 446), type 2 diabetes mellitus on diet (n = 95), type 2 diabetes mellitus on insulin therapy (n = 134), gestational diabetes mellitus on diet (n = 1652), gestational diabetes mellitus on insulin therapy (n = 735), preeclampsia (n = 39), and the control group (n = 139). The examined placentas were weighed, with their sizes (two diameters and thickness), cotyledon structure and defects assessed. We determined the umbilical cord junction and external characteristics of extraembryonic membranes. Fragments of the placenta (5 pieces) were fixed in 10% neutral buffered formalin (pH 7.2), processed with the Leica TP1020 tissue processor and embedded in paraffin. Histological sections (3-4 m thick) were prepared and stained with hematoxylin-eosin. Statistical analysis was performed using the SPSS 23.0 and GraphPad Prism 8.0 software. RESULTS: Following characteristics were typical for all types of diabetes mellitus: increased placental mass metrics, chronic placental insufficiency, dissociated villous maturation disorder with prevalent immaturity, as well as involutive-dystrophic and circulatory disorders of varying severity. Placentas from women with type 1 diabetes mellitus had the specific sings: the predominance of intermediate immature villi and stem villi stromal fibrosis. The frequency of placental infarcts and fibrinoid content in the intervillous space were comparable to those in placentas from women with type 2 diabetes mellitus. Inflammatory changes and moderate placental calcification were most consistently associated with type 2 diabetes mellitus, while gestational diabetes mellitus was characterized by soft damages. Placentas with preeclampsia showed higher prevalence of premature villous maturation, compensated placental insufficiency, and fibrinoid depositions in the intervillous and subchorionic spaces. CONCLUSIONS: Understanding relationships between placental histological features and clinical aspects of diabetes mellitus makes it possible not only to clarify the pathophysiological processes occurring in this pathology but also to optimize the algorithm for the rational management of the neonatal period of children from mothers with diabetes mellitus.

Study Objective: To analyse risk factors and perinatal mortality structure in patients with various types of diabetes mellitus (DM) over the last 30 years in specialised settings. Study Design: retrospective single-site cohort study. Materials and Methods. We have studied 42 medical records containing cases of perinatal death of foetus or newborn in 1988–2018 in patients with DM1 (n = 20), DM2 (n = 10), gestational DM (n = 12). Study Results. The most common complication in pregnancy was preeclampsia combined with chronic placental insufficiency (47.6%). The most common risk factors of perinatal death were inadequate glycemic control in 1st trimester (69.0%), absence of preconception preparations (66.7%), preconception overweight and obesity (42.8%), and chronic arterial hypertension (28.6%). There were 38.1% antenatal deaths, 16.7% intranatal deaths, and 45.2% cases of postnatal mortality. The major causes of perinatal foetal mortality in 26.2% cases were placental disorders, 16.7% were associated with foetus growth retardation, diabetic fetopathy and respiratory distress syndrome. Conclusion. DM during pregnancy was associated with a higher risk of perinatal death. Timely preconception preparation, BMI normalization and a consolidated approach to term and mode of delivery can reduce the risk of perinatal mortality in women with various types of DM. Keywords: diabetes mellitus, gestational diabetes mellitus, perinatal mortality, stillbirth, obesity, preeclampsia

AIM: The aim of this study was to evaluate soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) levels in the blood of women with various types of diabetes mellitus, depending on the correction method applied, and to determine the prognostic significance of the sFlt-1 / PlGF ratio for predicting the development of preeclampsia in this patient population. MATERIALS AND METHODS: We examined 140 pregnant women who were included in six main study groups: type 1 diabetes mellitus (with or without pregravid preparation), type 2 diabetes mellitus (diet therapy or insulin therapy), and gestational diabetes mellitus (diet therapy or insulin therapy). The comparison groups consisted of pregnant women with preeclampsia and patients without complications of pregnancy. Using electrochemiluminescence analysis, PlGF and sFlt-1 levels in the blood serum were determined twice, at 11+013+6 and 30+033+6 weeks of gestation. Statistical data processing was performed using the IBM SPSS Statistics version 23 and GraphPad Prism version 8.0 software packages. RESULTS: In the blood serum of pregnant women with diabetes mellitus in the first and third trimesters of pregnancy, we found an increase in sFlt-1 level and a decrease in PlGF level, as well as an increase in the sFlt-1 / PlGF ratio. These changes were most pronounced in individuals with type 1 diabetes mellitus without pregravid preparation and with type 2 diabetes mellitus on insulin therapy. In patients with pregestational types of diabetes mellitus, the sFlt-1 / PlGF ratio was a predictor of preeclampsia already in the early stages of pregnancy. Analysis of the ROC curve showed that the threshold sFlt-1 / PlGF ratio for predicting preeclampsia in pregnant women with diabetes mellitus in the first trimester was 32.5 (sensitivity 92.9%, specificity 50.0%) and in the third trimester 71.8 (sensitivity 85.7%, specificity 82.3%) with AUC 0.78 (95% CI 0.680.88) and 0.89 (95% CI 0.830.95), respectively. In the first trimester, the positive and negative predictive values of the sFlt-1 / PlGF ratio as a predictor of preeclampsia in pregnant women with diabetes mellitus were 63.3% and 97.6%, respectively; in the third trimester, 38.9% and 93.6%, respectively. CONCLUSIONS: Blood level alterations of PlGF and sFlt-1 are characteristic of patients with diabetes mellitus in the first and third trimesters of pregnancy. An increase in the sFlt-1 / PlGF ratio is associated with a higher incidence of unfavorable perinatal outcomes in women with impaired carbohydrate metabolism. Determination of the sFlt-1 / PlGF ratio is a valid method for predicting the development or absence of preeclampsia in women with diabetes mellitus.

BACKGROUND: The high risk of adverse maternal and perinatal complications in patients with fetal growth restriction and diabetes mellitus requires a detailed assessment of the major risk factors and outcomes. AIM: The aim of this study was to determine the main risk factors for fetal growth retardation in pregnant women with pregestational and gestational diabetes mellitus, and to assess obstetric and perinatal outcomes in these patients. MATERIALS AND METHODS: We conducted a retrospective single-center cohort study at the premises of the Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott, Saint Petersburg, Russia. The study included 103 patients with type 1 diabetes mellitus, type 2 diabetes mellitus, or gestational diabetes mellitus with fetal growth retardation who delivered a singleton neonate from January 2017 to December 2021. Based on the antenatal diagnosis, the patients were divided into the following comparison groups: group I early fetal growth retardation (n = 29), group II late fetal growth retardation (n = 27), group III small for gestational age (n = 47). Relative risk calculations were used to assess the contribution of risk factors and the risk of developing secondary outcomes. RESULTS: Pregestational diabetes mellitus was the major risk factor for early fetal growth retardation development (relative risk 1.91; 95% confidence interval 1.043.50); especially type 1 diabetes mellitus (relative risk 1.64; 95% confidence interval 1.022.74) and more than 10 years of pregestational diabetes mellitus duration (relative risk 2.62; 95% confidence interval 1.126.17). Chronic hypertension increases the risk of early fetal growth retardation (relative risk 2.11; 95% confidence interval 2.213.68), while gestational hypertension was a significant risk factor for late fetal growth retardation development (relative risk 1.81; 95% confidence interval 1.013.70). Preeclampsia is associated with both early and late forms of fetal growth retardation. Maternal characteristics, such as age over 35 years, obesity, and in vitro fertilization pregnancy, increased the risk of early fetal growth retardation development. In turn, the presence of fetal growth retardation in patients with diabetes mellitus is associated with increased risk of cesarean section, prolonged stay of the newborn in the neonatal intensive care unit (5 days), low Apgar scores (7 at the 5th minute), and neonatal hypoglycemia. Early fetal growth retardation is a significant risk factor for preterm birth (relative risk 6.23; 95% confidence interval 2.8713.42) and fetal distress (relative risk 5.51; 95% confidence interval 2.2813.33). CONCLUSIONS: Being associated with a highly increased risk of adverse obstetric and perinatal outcomes, early fetal growth retardation in diabetic pregnancy is related to pregestational diabetes mellitus, especially type 1 diabetes mellitus, with a long history, as well as with hypertension in pregnancy.