Ставропольский государственный медицинский университет, Российская Федерация 2 медико-генетический научный центр им. академика Н. п. Бочкова, москва, Российская Федерация feaTures of ViTamin D proVision of chilDren WiTh cYsTic fiBrosis resiDing in The souTh of russia in summer Dolbnya s. V. 1 , Dyatlova a. a. 1 , Klimov l. Ya. 1 , Kondratyeva e. i. 2 , Kuryaninova V. a. 1 , Tsutsaeva a. n. 1 , enina e. a. 1 , Zodbinova a. e. 2 1 stavropol state medical university, russian federation 2 research center for medical genetic, moskow, russian federation В исследование включено 30 пациентов с муковисцидозом (МВ) (средний возраст 8,3±5,1 лет) и 30 здоровых детей (средний возраст 7,1±5,3 лет), проживающих в Ставропольском крае в летнее время года. Оценка обеспеченности витамином D проводилась по содержанию кальцидиола -25(ОН)D в плазме крови.Недостаточность витамина D менее 30 нг/мл обнаружена у 15 (50,0 %) больных муковисцидозом и у 4 (13,3 %) здоровых детей. Уровень 25(ОН)D пациентов с МВ, не получающих препараты витамина D, составлял 15,9 [12,6-17,1] нг/ мл, у здоровых детей -24,6 [19,8-29,9] нг/мл (р=0,001). Средняя саплементационная доза холекальциферола у пациентов с МВ составляла 3080,0±257,7 МЕ/сутки, у здоровых детей -1468,8±132,8 МЕ/сутки (р=0,0007), при этом обеспеченность витамином D больных с МВ была 32,3 [25,7] нг/мл, а здоровых детей -36,7 [34,9] (p=0,03). Уровень витамина D в сыворотке коррелирует с возрастом (в группе детей с МВ r=-0,47, р=0,009, в контрольной группе -r=-0,44, p=0,016).Исключительно естественная инсоляция не позволяет поддерживать оптимальный уровень 25(OH)D сыворотки ни у здоровых детей, ни у больных МВ. Препараты холекальциферола эффективно восстанавливают обеспеченность витамином D, однако доза должна подбираться индивидуально. Обеспеченность витамином D пациентов с МВ зависит от возраста, вероятность дефицита витамина D возрастает по мере взросления ребенка.

Vitamin D has pleiotropic effects, including maintaining calcium and phosphate homeostasis, and affecting the immune and endocrine systems. The article summarizes data on the expected biological effects of vitamin D on children’s health. The results of randomized clinical trials evaluating the effect of vitamin D supplementation on the incidence of acute respiratory tract infections are reviewed in detail. It has been shown that daily intake of vitamin D at a dose of 10 to 25 mcg/day (400–1000 IU/day) compared with placebo leads to a significant decrease in the proportion of children and adolescents who have had at least one episode of acute respiratory infection. The criteria for the provision of calciferol and the gradation of the status of vitamin D deficiency and deficiency in different countries are discussed. It has been shown that in the interpretation of the 25 (OH) D results there is a consensus on two points: calcidiol levels below 12 ng/ml (30 nmol/L) are considered clearly insufficient, and levels above 30 ng/ml (75 nmol/L) are considered sufficient in all regions. The incidence of hypovitaminosis D has been reported in children aged 3 to 7 years, where the overall combined assessment, regardless of age group, ethnic composition and breadth of the studied populations, showed that 13% of European children had a serum calcidiol concentration of less than 12 ng/ml (<30 nmol/L), and about 40% had a level of less than 30 ng/ml (<75 nmol/L). The data on the physiological need and the recommended daily dose of vitamin D for preschool children have been analyzed. In each country, the recommended intake of vitamin D is set (from 400 to 4000 IU), depending on the target concentration of serum calcidiol, the level of insolation, and nutritional characteristics. The necessity of conducting clinical studies in the age group from 3 to 7 years to determine an adequate, effective and safe preventive dose of vitamin D for preschool children in the Russian Federation is emphasized.

The study included 78 children: 38 patients with cystic fibrosis (CF) (median age 8.2 [4.9-13.8] years) and 40 healthy children (median age 7.66 [2.0-12.1] years), living in the Stavropol region during 2018-2019. Vitamin D sufficiency was assessed by the content of calcidiol -25(OH)D in blood plasma. Seasonal fluctuations in the level of calcidiol during the year in children with CF were more pronounced than in children from the control group -12.2 [7.6-20.2] ng/ml in winter, 29.8 [21.3-37 .9] ng/ml in spring, 33.2 [26.5-39.1] ng/ml in summer and 22.6 [11.4-30.5] ng/ml in autumn, in healthy children the level is 25(OH)D during 2018 was 34.8 [24.8-53.1] ng/ml in winter, 31. 1 [24.6-44.6] ng/ml in spring, 30.4 [23.3-35.3] ng/ml in summer and 41.9 [32.1-55.2] ng/ml in autumn. Serum calcidiol levels were significantly lower in CF children compared to the control children group in winter (p=0.007) and autumn (p=0.04). During the study, the number of children with vitamin D deficiency and severe vitamin D deficiency significantly decreased. At the beginning of the study, severe vitamin D deficiency was detected in 40 % of patients with CF; after adjusting the dose of vitamin received in spring (p<0.005) and summer (p<0.005), it was not found in any of the children. On the contrary, the frequency of normal vitamin D sufficiency increased significantly by 36.7 % in spring (p<0.05), by 50 % in summer (p<0.01), and by 16.7 % in autumn (p>0.05), compared with the first determination of 25(OH)D in winter. Thus, the frequency of vitamin D deficiency in CF patients is statistically significantly higher than in healthy children. The problem of vitamin D deficiency in children with CF is quite relevant due to the low awareness of CF patients and their parents about the critical role of cholecalciferol in this disease.

Celiac disease (CD) is characterized by the formation of an anemic syndrome whose etiopathogenesis if of a multifactorial origin. The main types of anemias in children with celiac disease are iron deficiency anemia (IDA) and anemia of inflammation, also called anemia of chronic disease (ACD). This bibliographical review presents current information on the iron metabolism, morphological changes in the epithelium of the intestinal mucosa in celiac disease leading to the development of iron deficiency, pathogenesis of ACD formation in celiac disease, as well as the diagnosis of IDA and ACD in celiac disease.

Case Discussion Though MIS-C is rare, with an incidence of 0.14% among children with SARS CoV-2 infection according to one Systematic Review (Hoang Et al. 2020), it is an important new differential which must be borne in mind in cases of fever with no clear source. Both of these cases had a negative PCR test for SARS CoV-2 and no history of Covid 19 disease. No serological testing for SARS CoV-2 was available in our hospital setting. But in accordance with RCPCH guidelines this does not exclude the diagnosis of MIS-CIn previous studies as many as 71% of cases of MIS-C required PICU admission (Ahmed Et al., 2020), however not all are severely unwell and may be stable enough to be managed on a ward setting as described above.

The conditions of human development during the stages of early ontogenesis are of great importance for human health throughout the rest of his life. The period of intrauterine development and childhood are vulnerable stages of organism formation, when metabolic processes have the greatest plasticity and can be subject to deformation. Exposure to a number of external factors during this period of time can have a significant impact on the functional activity of genes controlling neurotransmission, immune response, endocrine functions and, thus, program the spectrum of metabolic disorders that can lead later to the formation of chronic diseases: obesity, type 2 diabetes, atherosclerosis and diseases of cardiovascular system. Negative programming influence on the metabolic profile and cardiovascular risk is caused by such factors as maternal obesity, complicated pregnancy and childbirth, prematurity, early separation from the mother, violation of child feeding in the 1st year of life. The risk of early development of cardiovascular disease, metabolic syndrome, obesity and diabetes mellitus is significantly increased in individuals who have experienced traumatic stressors during childhood associated with economic disadvantage of the family, parental divorce, neglect, abuse, parental neglect, sexual violence, death of parents, family members, close friends, bullying in the children's community. An in-depth study of this problem, along with the development and organization of measures for monitoring and prevention, in the long term can reduce the burden of chronic non-infectious diseases, improve quality of life, reduce disability, incapacitation and mortality in the adult population..

To date, the most discussed issue is the rational dosage and duration of cholecalciferol preparations course for the correction and prevention of hypovitaminosis D. Objective of the research: to compare the structure of provision and the median 25 (OH) D before (2013–2016) and during the introduction into clinical practice (2018–2019) of the National Program Vitamin D Deficiency in Children and Adolescents in the Russian Federation: Modern approaches to correction» in young children. Materials and methods: the study had two stages. The first stage took place as a part of the RODNICHOK2 study from 2013 to 2016 before the implementation of the National Program «Vitamin D Deficiency in Children and Adolescents in the Russian Federation: Modern Approaches to Correction». The second stage of the study took place in 2018–2019 during the implementation of the National Program in clinical practice. The study participants were 246 children aged from 1 month to 3 years who took cholecalciferol preparations. The assessment of calcidiol concentration in the blood serum was assessed by the method of chemiluminescence immunoassay (CLIA) using reagents Liaison® 25OH Vitamin D Total Assay on the Liaison Dia Sorin Pleutschland GmbH device in the centralized laboratory of Scientific Center EFIS Ltd, Moscow. Results: during the introduction into clinical practice of the National Program, the frequency of prescribing a dosage of 500 IU/day significantly decreased to 4,9% (χ2=80,4, p<0,001), 1000 IU/day – statistically significantly increased to 71% (χ2=53,5; p<0,001), and a dose of 1500 IU/day was taken by 24% of children, mainly in the second and third years of life. In children examined in 2013–2016, the median serum calcidiol was 29,1 [22,8; 39,5] ng/ml, statistically significantly lower than in 2018– 2019, – 51,3 [38,1; 61,5] ng/ml (p<0,001). Hypovitaminosis D in young children in southern Russia until 2018 was diagnosed in 54,9%, statistically significantly more often than during the implementation of the National Program – in 12.2% of children (χ2=24,3, p<0,001). The number of children with a calcidiol level of more than 30 ng/ml, on the contrary, statistically significantly increased from 45,1 to 87,8% (χ2=39,9, p<0,001). There was a statistically significant decrease in the number of children with vitamin D deficiency – only 10 (12,2%) cases, while earlier their number was 62 (37,8%) (χ2=17,3, p<0,001). Among children examined in 2018–2019, it was possible to completely eliminate severe deficiency (calcidiol level less than 10 ng/ml) and vitamin D deficiency (10–20 ng/ml), while previously it was revealed in 6 (3,7%) (χ2=220,8, p<0,001) and 22 (13,4%) children (χ2=167,9, p<0,001). In 2013–2016 the indicator of the recommended average daily dosage of vitamin D was 73,3 [51,6; 103,1] IU/kg per day, while in 2018–2019. During the implementation of the recommendations set out in the National Program – 125,0 [102,0; 148,7] IU/kg per day (p<0,0001). Conclusion: the study confirmed daily doses per kilogram of body weight in the range from 100 to 150 IU/kg, included in the main provisions of the recommendations for prophylactic intake of vitamin D preparations at an early age. The introduction of the recommendations on the prophylactic course of vitamin D supplementation described in the National Program «Vitamin D Deficiency in Children and Adolescents in the Russian Federation: Modern Approaches to Correction» into wide clinical practice allowed to achieve a significant increase in the number of children receiving additional vitamin D supplements. The recommended average daily dose in comparison with the period before the implementation of the National Program has increased statistically significantly.