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According to the concept of D. Barker, the intrauterine period is decisive in the programming of postnatal pathology, which can manifest during life. Among the factors of fetal programming, the microbiota plays an important role, but many aspects are still debatable. Objective: analysis and generalization of literary data devoted to the study of the association between the human body and microorganisms, their characteristics during pregnancy and their role in the health and pathology. According to the literature analysis, the article provides data on the non-sterility of the intrauterine environment and ways of its formation. The dynamics and features of “healthy” biotopes of intestines, vagina, mouth and placenta during pregnancy are considered. The main ways of fetus colonization by microorganisms are described, in particular, a major role is given to oral microflora. The effects of prenatal microbiota in physiological and complicated pregnancy, namely in preeclampsia, gestational diabetes, and miscarriage are discussed. Evidence is provided that microbial metabolites are capable of epigenomic modifications that alter fetal metabolism. This is further realized in the diseases of civilization. In addition, there are 360 times more bacterial genes than human genes. Therefore, they are called the “second genome” of a human, which can be changed according to needs. Modern research points to the essential importance of the maternal environment impact on the formation of microflora in fetus and pathology programming, and this process begins in utero. Maternal microbiota in normal and pathological conditions has a direct and indirect effect on the fetus through the immune reactions of the body or microbial metabolites penetrating through the placenta. Conclusions. The importance of microbiota in the metabolic processes of the fetus and newborn is extremely important. Microbiota also plays a significant role in the main pathophysiological aspects of programmed pathology. The development of correct preventive and therapeutic measures to modify the “healthy” microbiota during periods of its active formation should be a perspective for further research. This will allow it to be corrected taking into account the characteristics of individual biotopes.

Backgraund: Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders found during pregnancy. Currently, it is relevant not only to search optimal target levels of glycemia during pregnancy, but also to study the ­effect of different glycemia levels on fetal development and further changes in glucose and lipid metabolism in children.Aims: To describe perinatal period, physical development and metabolic status of children born to women with GDM and different glucose levels during pregnancy.Materials and methods: The perinatal period features and anthropometric parameters at birth were evaluated in 300 children born to women with GDM and different levels of glycemia during pregnancy. Over the course two years, 141 children have been evaluated for physical development parameters and glucose and lipid metabolism. Fasting and postprandial glycemia was measured with glucometer for 14 days in 33 children aged 1 to 4 years.Results: The anthropometric parameters of children at birth did not differ from the parameters of the control group (p> 0.05) when during pregnancy fasting blood glucose was less than 5.1 mmol / l and 7.0 mmol / l 1 hour after a meal. The glycemia in women above this level was associated with an increase of frequency and risk of a body mass index, body mass / length ratio and head circumference “above average” in children at birth (p 0.05). The change in metabolic parameters was represented by neonatal hypoglycemia in children of GDM group (GDM group — 23%, control group — 3.5%, p = 0.000002), the least risk of which occurred in group with the lowest fasting and postprandial glycemic values during pregnancy. Fasting glucose, and insulin levels, НOMA index, triglycerides and cholesterol, as well as monitoring fasting and postprandial glycemia for 14 days, were obtained no significant differences between the comparison groups of children (p> 0.05).Conclusions: The lowest risks of neonatal hypoglycemia and anthropometric deviations at birth were associated with the lowest glycemia levels during pregnancy, which correspond to the criteria of the Russian clinical guidelines.

The article presents the literary review of domestic and foreign sources on fetal programming. Intrauterine programming is the in utero phenomenon that determines the subsequent susceptibility of the body to chronic and acute diseases, which is laid down at the cellular and molecular levels. Currently, this direction is promising and relevant due to the decrease in fertility rates in many countries, the emergence of a large number of low birth weight children and the postponement of childbearing by women to a later age. The article discloses the influence of excess and underweight at birth on the frequency and structure of diseases in adulthood, as well as the key links in the formation of insulin resistance, type 2 diabetes mellitus, obesity, osteoporosis, diseases of the cardiovascular system, which are based on various disorders of intrauterine development. The reasons for these disorders are changes in the synthesis of fetal and placental hormones, which regulate metabolism (with a deficit in body weight - the catabolic orientation of metabolism), redistribute blood flow and control growth. The main factors influencing the programming of diseases in the fetus are: nutritional status of the mother, the functioning of the feto-placental system, stress, bad habits, the state of the endocrine and immune systems. Particular attention is paid to the intrauterine effect of hormones such as insulin, cortisol, growth hormone and the renin-angiotensin-aldosterone system. The present-day data on the role of essential amino acids, vitamins and microelements in the development of diseases in adulthood are presented. The negative influence of both insufficient and excess vitamins on the intrauterine development of the fetus is shown, and the optimal terms for correcting their balance are indicated.

The article provides information on the main groups of vitamins and their effects on the child’s body. The negative effect of the macroand micro-elements deficit on the human body, both of the adults and children, has been proved convincingly. The essential triad of vitamins (A, C, D,) is the most significant vitamins for children under one year. This combination of vitamins ensures the safety of the combination and the possibility of mutual supplement of ingredients for effective formation of infant immunity, neuropsychic development, harmonious physical development and prevention of rickets. The vast majority of children under one year have an essential vitamins A, C, D deficiency, regardless of the nature of feeding. The Russian studies showed that only 45.6% of children have an adequate vitamin D level. It is also proven that children with atopic dermatitis have low vitamins A, C, and E levels.

A high prevalence of vitamin D deficiency and its negative consequences for health is identified as area of primary concern for scientists and clinicians worldwide. Vitamin D deficiency affects not only bone health but many socially significant acute and chronic diseases. Observational studies support that pregnant and lactating women, children and teenagers represent the high risk groups for developing vitamin D deficiency. Current evidence highlights a crucial role of vitamin D in providing the fetal life-support system and fetus development, including implantation, placental formation, intra - and postpartum periods. Hypovitaminosis D during pregnancy is associated with a higher incidence of placental insufficiency, spontaneous abortions and preterm birth, preeclampsia, gestational diabetes, impaired fetal and childhood growth, increased risk of autoimmune diseases for offsprings. Potential mechanisms for the observed associations contain metabolic, immunomodulatory and antiinflammatory effects of vitamin D. Epigenetic modifications in vitamin D-associated genes and fetal programming are of particular interest. The concept of preventing vitamin D deficiency is actively discussed, including supplementation in different ethnic groups, required doses, time of initiation and therapy duration, influence on gestation and childbirth. An adequate supply of vitamin D during pregnancy improves the maternal and fetal outcomes, short and long term health of the offspring. Still current data on relationship between maternal vitamin D status and pregnancy outcomes remains controversial. The large observational and interventional randomized control trials are required to create evidence-based guidelines for the supplementation of vitamin D in pregnant and lactating women.

Due to the growth of non-infectious morbidity of the world’s child and adult population, the concept of nutritional programming connecting cardiovascular and certain endocrine diseases with the fetoplacental complex disorders in the antenatal period has been developed over the past 25 years. An increase in the prevalence of obesity and gestational diabetes in pregnant women lays the groundwork for an increase in the prevalence of glucose metabolism disorders and the risk of endocrine pathology in children. Both low weight and overweight at birth evidence the unfavourable course of the intrauterine period. The review discusses the factors contributing to the fetal organs and systems growth retardation, hypovitaminosis D, insulin resistance and possible mechanisms for their development. The authors present the analysis of the data available in the modern literature on the mechanism of the obesity and GDM programming effect on the diseases in new-borns and children.

In recent years there is notable growing prevalence of gestational and overt diabetes in pregnant women while rate of obstetric complications, neonatal morbidity, perinatal mortality in women with diabetes is maintained at the high level as compared with common population. Furhermore no doubt that fetal programming and genetic factors induce the formation of various longterm complications in infants of diabetic mothers. There is a strong evidence that the risk of obstetric complications can be reduced by achieving adequate glycemic control, which is frequently still an elusive goal. Improved pharmacokinetic and pharmacodynamic profiles of the insulin analogs (including minimal action variability) allow to achieve a better glycemic control with lower risk of hypoglycemias compared to human insulin. The clinical benefits of detemir have been confirmed in clinical trials in pregnant women with diabetes. Detemir is the only long-acting insulin analog that has been evaluated in prospective studies in pregnant women and proved a satisfactory safety profile and the ability to achieve a lower level of fasting glycemia and advanced maturity of the fetus at delivery.