The article presents data on the clinical and pathogenetic variants of fetal growth restriction (FGR). FGR is one of the typical clinical manifestations of large obstetric syndromes, is associated with a high perinatal morbidity and has a significant impact on the quality and duration of human life. The emphasis is made on the differences in pathogenesis, the features of prediction, diagnosis, obstetric management and the assessment of perinatal outcomes in the early and late phenotype of the FGR. The review includes materials from domestic and foreign scientific literature that found in eLibrary and PubMed on this topic and published for the last 10 years. This article discusses the role of the formation of the embryo(feto)placental system under the influence of existing periconceptional risk factors in the implementation of various phenotypes of FGR. An analysis of the literature shows that the fetal growth potential, which genetically and epigenetically determined, changes during pregnancydepending on maternal, placental and fetal factors, which ultimately determine the final weight-growth parameters of the newborn. The issues of informativeness of clinical, laboratory and instrumental predictors, diagnostic criteria, the choice of rational obstetric management in case of FGR of various periods of manifestation are discussed in this article. Convincing data on the perinatal and long-term consequences of intrauterine growth restriction are presented. The pathogenetic variant of FGR determines the features of the functioning of the immune system, has a significant impact on the programming of metabolic and endocrine processes, the formation of fetal brain structures. Identification of pregnant women at risk for the development of FGR of various periods of manifestation, timely diagnosis, selection of the timing and method of delivery should correspond to the main directions of the "4P-model" of modern medicine and represent an integral predictive, preventive and personalized system of examination and observation based on evidence-based medicine data and the requirements of practical obstetrics and perinatology.

Introduction. Pre-eclampsia (PE) continues to be the leading problem in obstetrics. The existing methods for predicting PE show insufficient efficiency, and therefore the search for new predictors of PE remains relevant.The goal of the study. To develop a method for staged stratification of pregnant women to the risk of PE according on the basis of the revealed dismetabolic features of the pathogenesis of this complication of gestation.Material and methods. A dynamic clinical and laboratory examination of 180 pregnant women with independent factors of high risk of PE was carried out. PE was revealed in 89 women who made up group I. Group II (control) consisted of 30 healthy pregnant women with the physiological gestation.Results and discussion. A statistically significant increase in diabetogenic and atherogenic changes characteristic of physiological pregnancy, changes in hormonal, endothelial-hemostasiological, pro-inflammatory and placental parameters aimed at the energy and plastic supply of the fetus was revealed in women with PE. The results of laboratory examination, statistical data processing showed that the most significant pathogenetic mechanisms of development of PE are pathological insulin resistance (IR) and hyperinsulinemia (HI), which act as the basic link and initiate atherogenic transformation of the lipid profile, pro-inflammatory and immunometabolic disorders, prothrombotic status, hyperleptinemia, hyperuricemia, antiangiogenic state and endothelial dysfunction, which indicates a  pronounced pathogenetic and clinical similarity of  PE and metabolic syndrome. The  revealed features of the pathogenesis of PE were reflected in the method of staged risk stratification of pregnant women: the models for assessing the individual risk of PE implementation included the levels of insulin, PlGF, PAMG-1, and TNF-α at 11–14 weeks of gestation; levels of insulin, uric acid, TNF-α, and mean platelet volume at 18-21 weeks of gestation (I trimester – AUC = 0.886, Se = 86.7%, Sp = 84.3%; II trimester - AUC = 0.874, Se = 83.3%, Sp = 87.2%, р < 0.001).Conclusion. Practical application of the developed pathogenetically substantiated method of staged stratification of pregnant women by the risk of PE implementation will justify the appointment and enhancement of preventive measures, reduce the incidence of severe and complicated forms of PE, and improve gestational and perinatal outcomes.

BACKGROUND: Modern achievements of pharmacology, surgery and reproductive medicine have determined an increase in the implementation of reproductive function in endometriosis of various localization. The onset of pregnancy in presence of impaired endometrial receptivity and progesterone resistance, pro-inflammatory and pro-thrombotic status, abnormal functioning of the immune system, structural changes in the reproductive organs leads to impaired formation of the embryo (feto) placental system, early reproductive losses, complicated pregnancy and adverse perinatal outcomes. In this regard, the endometriosis and pregnancy issue requires close study and specific proposals to optimize pregnancy management. AIM: The aim of this study was to develop predictive (PIs) and diagnostic (DIs) indices of placenta-associated fetal pathology in pregnant women with endometriosis, to determine their prognostically and diagnostically significant parameters. MATERIALS AND METHODS: This prospective study in the dynamics of gestation included a comprehensive clinical and laboratory examination of 175 pregnant women with endometriosis (100 subjects with adenomyosis and 75 subjects with ovarian endometriosis). To develop PIs and DIs, two comparison groups with fetal pathology due to placental insufficiency were retrospectively identified, depending on the location of endometriosis. Group I consisted of 49 pregnant women with adenomyosis and placental insufficiency isolated from other pregnancy complications, accompanied by growth retardation and/or chronic fetal hypoxia; Group II comprised 29 pregnant women with ovarian endometriosis and placental insufficiency isolated from other pregnancy complications, accompanied by growth retardation and/or chronic fetal hypoxia. The control group (Group III) included 30 healthy pregnant women with a normal course of gestation. The examination was performed at 10-14 weeks, 20-24 weeks, and 28-34 weeks of gestation and included an assessment of placental insufficiency markers such as placental growth factor (PlGF), placental -1-microglobulin (PAMG-1), tumor necrosis factor (TNF), lymphocytes with membrane receptor FasR (L CD95+), C-reactive protein, placental alkaline phosphatase (PAPh), and fetal hemoglobin (HbF). The information value of individual parameters and indices was determined by ROC analysis, odds ratio, and clinical epidemiology tests. RESULTS: Pregnancy in presence of endometriosis in 100% of cases was complicated by placental insufficiency of varying severity (with fetal pathology in 81.5% of cases), the frequency of which had statistically significant differences between the groups of pregnant women with adenomyosis and ovarian endometriosis (2 = 4.06, p = 0.04). To predict growth retardation and / or chronic fetal hypoxia, we have developed PI I (PlGF / TNF 100) and PI II (PAMG-1 / PlGF 100), which characterize the state of placental angio-and vasculogenesis depending on systemic inflammatory response level. For early diagnosis of fetal pathology, we have proposed DI I (CRP / PAPh 100), DI II (HbF / PlGF 100) and DI III (L CD95+ / PAPh 100), which allow for diagnosing placental alterations with impaired placental energy supply due to an increase in inflammatory status. Evaluation of prognostic and diagnostic significance of PIs and DIs showed that the most informative tools are PI I (Se = 86.1%, Sp = 80.5%) and DI I (Se = 88.3%, Sp = 83.7%). CONCLUSIONS: The use of PIs allows for risk stratification of pregnant women from the 1st trimester of gestation to address the issue of the prevention method. The clinical capabilities of DIs optimize obstetric tactics for the timely prescription of therapy for placental insufficiency and targeted diagnosis of fetal pathology. Pregnant women with endometriosis should be classified as a high perinatal risk group, and therefore the proposed PIs and DIs should be included in the dynamic examination complex.