[MENTAL AND SPEECH DEVELOPMENT IN CHILDREN LIVING IN ECOLOGICALLY UNFAVOURABLE REGIONS OF GEORGIA].

The ecological condition of different cities and regions in Georgia is variable. The level of anthropogenic contamination with xenobiotics in most of them significantly exceed the normal level. In almost 25% of children residing in Tbilisi, Batumi and Kutaisi the level of xenobiotics varies 5.0-10.0 mkg/dL, 16% of children have higher than 10.0 mkg/dL. We have studied the profile of mental and speech development in children living in abovementioned cities according to the level of Pb in blood. On the basis of representative selection we have studied the level of Pb in the range of 5.0 mkg/dL and 10.0 mkg/dL for two groups of children with normal development: 65.5 months- (I study group) and 89.5 months (II-study group). Control group has no Pb in blood. The situation in family was also considered. Intellectual development was assessed by Wexler verbal and nonverbal subtests, neuropsychological methods by Luria-Kristensen and visual-motor and visual-spatial evidence by WBAVMA. According to results of children from group I living in ecologically unfavourable regions average evidence for mental and speech verbal awareness were within normal range and similar to controls. As for group II the difference from normal age range was not found. The development of awareness of false belief of second order for group-I was significantly delayed which could occur due to pitfalls in cognitive field. The redevelopment of structure of motivated behaviour in children from group-I was significantly restricted compared with group-II and controls.

[NEUROLOGICAL DISORDERS OF CHILDREN LIVING IN ECOLOGICALLY AFFECTED REGION OF GEORGIA].

Article discussed the clinical evidence of children with attention deficit hyperactivity disorder (ADHD) living in different regions with polluted air. We have revealed the correlation between severity of neurological impairment and level of Hg, Pb, Zn and Cu in blood of children of three different age group (2-5y, 6-9 y and 10-13y). According to our results we found correlation between living area and level of xenobiotics and essential microelements. Thus we have concluded that beyond the level of xenobiotics and essential microelements in child's blood their primary and secondary role in the development of neurological disorders in regions of various anthropogenic impact has to be considered.

VITAMIN D STATUS AMONG GEORGIAN CHILDREN WITH HIGH ACUTE RESPIRATORY MORBIDITY.

Vitamin D deficiency has been identified as a common metabolic/endocrine abnormality. There aren't any published data about vitamin D plasma level in Georgian population. Present study was conducted to reveal vit D status among Georgian children with high acute respiratory morbidity. The prospective observational study was performed by comparing serum vitamin D levels in children with recurrent respiratory infections (Upper respiratory infections, bronchiolitis, bronchitis, pneumonia) and healthy children in two cities of Georgia - Tbilisi and Rustavi. The 2 cohorts of 277 children at age from 3 months to 15 years were investigated. First cohort formed - 147 children with recurrent respiratory infections. 130 healthy children were included in control group (II cohort). One moment blood concentrations of 25-hydroxyvitamin D was determined in every study participant. The mean serum 25(OH) vitamin D level in the I age group with respiratory infections was 14.47±5.44 ng/ml and control group data were - 35.54ng/ml±8.66. In II age group with respiratory morbidity vit D level was 12.43±5.27 ng/ml and control group data were 27.71±18.29 ng/ml. In III age group mean serum 25(OH) vitamin D level was - 14.39±4.60ng/ml. Control group data - 28.31±12.59ng/ml. Comparison of serum 25(OH) vitamin D levels between the study groups (I cohort vs II cohort) revealed a statistically significant difference (p<0.05). In 14% of healthy adolescents from group III the vit D plasma level was <20 ng/ml (16±11.5 ng/ml). 25(OH)D deficiency in children was associated with high morbidity with respiratory infections. After 5 years of age most of the healthy children with the low respiratory morbidity in Georgian rural regions reveal Vit D insufficiency, especially in adolescent period.

INFLUENCE OF VITAMIN D ON HUMAN HEALTH (REVIEW).

Objectives - the associations between vitamin D concentrations and respiratory diseases have been assessed in a large and rapidly expanding literature. Observational studies and numerous randomized trials. Data sources: - Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomized Controlled Trials Number registry from 2011 to 2021. Vitamin D plays an essential role in maintaining bone health through regulating calcium concentrations in the body. The development of vitamin D deficiency is associated with deteriorating bone health and in severe cases, hypocalcemia, rickets, and osteomalacia in children and adults. Those at greatest risk of vitamin D deficiency include patients with chronic illnesses (e.g., chronic kidney disease, cystic fibrosis, asthma, and sickle cell disease), dark-pigmented skin, poor nutrition, and infants who are exclusively breastfed. The primary source of vitamin D is sunlight exposure with nutritional intake. However, the composite literature is often confusing and has led to heated debates about the optimal concentrations of vitamin D and related guidelines for supplementation. According to the last period of research, the impact of vitamin D is actively discussing the correct functioning of the immune system. It is established that it participates in the formation of the innate and adaptive immune response. In last years appeared data from controlled trials where there are confirmed D hypovitaminosis correlations with infections. The systemic review of the randomized controlled trials and meta analysis showed the effectiveness of vitamin D supplementation for reducing morbidity with respiratory diseases. In literary sources, the impact of Vitamin D is considered to influence the duration and severity of pneumonia. The authors note that in the cases of severe and complicated pneumonia, the concentrations of vitamin D was significantly lower than in control cases. It has been proposed that the activation of the vitamin D receptor (VDR) signaling pathway may generate beneficial effects in ARDS caused by SARS-CoV-2 with decreasing the cytokine/chemokine storm, regulating the renin­angiotensin system, modulating neutrophil activity. The systemic review of the randomized controlled trials and meta analysis showed the effectiveness of vitamin D supplementation for reducing morbidity with respiratory diseases. But most of researchers have concluded that data remain uncertain and requires confirmation in farther well designed randomized controlled trials.

ASSESSMENT OF KNOWLEDGE LEVEL AMONG GEORGIAN PARENTS ABOUT VITAMIN D INFLUENCE ON CHILD'S HEALTH. QUESTIONNAIRE SURVEY.

The present study was aimed to determine the parents' knowledge level about vit D importance for children normal health state, functions of vit D, sources, recommended duration of supplementation or treatment.The questionnaire was utilized as cross-sectional survey to determine the awareness of parents about vit D influence and importance for child health. The questionnaire was designed by the author. The survey questions covered the topics of parents'/caregivers' information needs; understanding of importance of vit D supplementation, causes of vit D deficiency, duration of supplementation, importance of screening adolescent girls for vit D deficiency. The survey was administered to parents/ caregivers of children of age from 1 to 15 years old living in Tbilisi and different regions of Georgia. The data were analyzed using Excel.A total 850 individuals participated in the study. Most of them 88,3% believed vit D to be important for health of a child, but could not explain why. 74% of respondents could identify oily fish or eggs as main source of vit D. However, 46% believed dairy products to be a good dietary source of vitamin D. More than 59% of participants supported their children by vit D drops up to age of 1 year, 40% by themselves decide to give it only 1-2-months. Only 12% of mothers continue to support her child by vit D till 24 months and more. About the importance for vit D deficiency prevention among adolescent girls, as for future mothers, 85,3 % of participants answered they have no information about this. According to received results, the parental awareness and level of knowledge about vit D importance for child normal growth and health is poor.Sothere is a need for increased levels of parental education to ensure children have a better chance of maintaining adequate vitamin D levels.

[MODERN INSUES OF ESSENTIAL TRACE ELEMENTS LEVEL INFLUENCE ON CHILDREN AND ADULTH HEALTH (REVIEW)].

Systematic review article reported that essential trace elements, mainly microelements Copper and Zinc (deficiency and high values concentration disbalance in blood) play significant roles in neurodevelopmental processes and are associated not only with inattention and hyperactivity, impulsivity symptoms among children and adolescents in the most critical active growth and development periods (between 3 and 16 years old). In the same time previous studies have proposed that clinical symptoms are significant associated their levels and positively correlated with cognitive symptomatology as trace bioactive substances. Their functional connectivity is different and is one of the serious problems for clinical pediatric.

[MODERN ASPECTS OF THE EFFECT OF XENOBIO-TICS ON CHILDREN AND ADOLESCENTS (REVIEW)].

The literature review presents data on the effect of organic and inorganic compounds, the so-called "main" xenobiotics (lead, mercury) on children and adolescents. It is noted that the effect of each heavy metal is different. Therefore, only their total assessment (blood, urine, saliva, hair, biological tissues) makes it possible to determine the level of toxic effects on the child and confirm the clinical decision. "Carrying mercury", in the absence of clinical signs of intoxication, does not always correlate with chronic poisoning. Ranking of clinical syndromes with the level of heavy metals in the body of children, monitoring of cause-and-effect relationships, detection of the prevalence of neurological changes becomes a priority in clinical Pediatrics. At the moment, the effects of heavy metals on the health of children and adolescents are a universal medical category. It forms the strategy of clinical pediatrics and pediatric neurology and a subject of interest for ecologists, toxicologists and sociologists.

Wilson disease with thrombocytopenia (case report).

We present an adolescent patient with WD accompanied with secondary amenorrhea, and thrombocytopenia. NK, a 14 year-old girl, had amenorrhea for 5 months despite having had regular menses for 2 years. An abdominal ultrasound scan revealed ascitis and some ovarian cysts. On physical examination: slight jaundice, edema of lower extremities, skin purpuric rash, enlarged abdomen, dry skin. She had no hepatomegaly and no splenomegaly. Breast and pubic hair development was concomitant with Tanner stage 4. There was performed laboratory and instrumental investigations. The patient was diagnosed as WD owing to the low level of ceruloplasmin, with increased level of copper in 24-hour urine excretion and in dry liver tissue. The needle biopsy of liver showed severe hepatocellular necrosis, inflammatory changes and fibrosis. The platelet count was found to be low with lack of increased number of megakaryocytes in the bone marrow aspiration suggesting the thrombocytopenia was not exclusively owing to hypersplenism. The absence of antithrombocyte and other autoimmune and viral antibodies excluded respectively the diagnosis of autoimmune thrombocytopenia, other autoimmune diseases and viral infections. Thus, we support the recommendation that adolescents with amenorrhea or children with thrombocytopenia without any obvious cause should be evaluated for WD, because the early detection and treatment of WD is capable of reversing described changes and restoring a normal liver function.

Cytomegalovirus bearing in children with sensorineural hearing losses.

The rate of bearing of cytomegalovirus, CMV, has been estimated in children suffering from inborn or newborn types of a sensorineural hearing loss of hard-to-severe degrees. The test group comprised 15 hearing-loss children of 3-6 years of age. The control group included accidentally selected 30 healthy children of the same age without any hearing complains. In both groups the CMV-specific IgG antibodies were determined in blood via the enzyme-linked immunosorbent assay, ELISA. The excessive amount of IgG antibodies was found in 14 out of 15 children with sensorineural hearing losses being estimated objectively, via computer registration of auditory brainstem responses, ABRs, and in 14 out of 30 children with normal hearing, being also inspected objectively, via specialized screening procedure. The intergroup difference in CMV bearing rates, 93.3% and 46.7%, respectively, has been confirmed to be statistically significant (p=0.007). CMV bearing happens thus twice as much in sensorineural hearing-loss than in normally-hearing children. Early detection of a hearing loss and early assessment of CMV bearing seem essential for an immediate start and, consequently, for a batter chance of positive outcomes of specific treatment-rehabilitation means.

[Blood biochemical changes in maternally deprived children and their emotional status].

Environmental rearing conditions during the neonatal period are critical for the establishment of neurobiological factors controlling behavior and stress responsiveness. Early maternal deprivation in animals consisting of a single 24-h maternal deprivation episode during early neonatal life has been proposed as an animal model for certain psychopathologies including anxiety, depression and schizophrenic-related disorders. The aim of the present research was to show the mechanisms how the early maternal deprivation in humans influences the emotional status of children. To understand the effects of early deprivation on the regulation of the hypothalamic-pituitary-adrenal axis of children following social interactions, we examined the blood neurotransmitters levels (Norepinefrin NA; Dofamin DF; Serotonin SE) in a group of healthy institutionalized children at age from 6 to 36 months from Tbilisi Infant's House. A group of healthy children of the same age from Mother & child shelters formed the control group. Emotional status was assessed by Leusher's Color Test in a group of healthy institutionalized children at age from 3 to 6 years from Tskneti Orphanage. Institutionalized children showed elevations in blood NE and decreased SE and DF concentrations in comparison with non deprived children's blood. The higher was percentage of children with high level of anxiety in the group of children from orphanage than in the children with family care. The results suggest that early maternal deprivation may contribute to long-term regulatory problems of the stress-responsive system that may be resulted in altered emotionality and behavior in deprived children.

Association between the cytomegalovirus seroprevalence and hearing loss in early childhood.

This study was designed to evaluate the association between the seroprevalence of CMV with the hearing loss among preschool children. A case-control study has been performed in Tbilisi, Digomi Inclusive Education Centre for children with hearing loss. The cohort of 15 children with SNHL was studied for HCMV specific IgG and IgM antibodies concentration in the blood. The control group consisted of 30 healthy children of the same age without any hearing abnormalities which have been tested on TORCH infections for screening purposes. The serum samples from all subjects were analyzed by enzyme-linked immunosorbent assay (ELISA). Comparison of seroprevalence rates for the study and control groups has been performed by Fisher's exact test. Seropositivity was almost two times higher among children with hearing loss in comparison with the children without any signs of hearing disabilities. CMV specific IgG antibodies were positive in 14 (93.3%) of 15 patients from the study group and in 14 (46.7%) of 30 children from the control group (p=0.003). Thus, CMV burden has been shown to be associated with the development of nongenetic sensorineural hearing loss. Early identification of children with CMV burden in early stages of development, as they are in increased risk for development the SNHL, is very important for early intervention and better outcome.

The intermittent and prolonged maternal separation affects behavioral reactions in rat pups.

The work was designed to reveal the effect of maternal deprivation on the behavioral reactions of rat pups during the intermittent and prolonged maternal separation. Research was conducted on 126 white rat pups of both sexes received from 26 mothers at the 1st, 15th, 21st, and 60th days after birth. All animals were divided into three main groups: the first group included 42 litters submitted to intermittent maternal deprivation (IMD). The second group included 28 litters submitted to prolonged maternal deprivation (PMD) and 56 litters served as the control group. Animals were housed in a room with a controlled temperature, humidity, 12 h light/dark cycle, having free access to the food and water. The received results testify to essential influence of maternal deprivation on the normal functioning of CNS, revealed in the alterations of behaviors in rats suffering from maternal deprivation. Thus, early maternal separation in rat pups may serve to be the stressful stimulus for CNS and alter it function, which produces the behavioural disorders among them.

[The comparative effect of continuous and intermittent maternal separation on catecholamines blood concentrations among rat pups].

Study was designed to show the affects of short-term intermittent and/or continuous maternal separation on norepinephrine and dopamine blood concentrations among rat pups. The 128 rat pups on the first, 15th, 21st, and 60th days after birth were investigated. Catheholamins blood concentration were measured by spectral fluorometry. The pathological changes in norepinephrine (NE) and dopamine (DA) plasma concentrations were exposed in both occasions - among rat pups with intermittent as well as with continuous maternal separation but were less pronounced in rat pups exposed to permanent maternal deprivation. The intermittent maternal separation produced a significant increase in plasma NE concentration compared to control non-deprived (p<0,001) and also to permanently deprived rats (p<0,01). While DA concentration, instead of elevation, was decreased in deprived rats. It was significantly lower in continuously deprived animals. The accentuated increase of NE suggests sympathetic nervous system hyperactivity, while decrease of DA indicates discoordination of the dopaminergic and sympathoadrenal systems in deprived pups. Thus, early maternal separation in rat pups may serve to be the stressful stimulus for CNS and alter it function, which produces the behavioral disorders among them.

[Procalcitonin - marker of severe infection and sepsis].

Systemic inflammatory response syndrome (SIRS), severe infection and sepsis are the problems of present interest in contemporary medicine. The specificity and sensitivity of widespread clinical and laboratory parameters are insufficient for diagnosing these diseases. A new marker for diagnosing of infective etiology of SIRS, severe infection and sepsis which allows early diagnosis and begin specific treatment is procalcitonin (PCT). In severe viral infections or inflammatory reaction of non-infective origin the level of PCT does not elevate or increases moderately. The level of PCT correlates with the severity of SIRS: the more severe the SIRS, the higher the level of PCT. The monitoring of PCT allows a rapid diagnosis of infective complications in patients after severe injuries or operations, in acute respiratory distress syndrome. PCT is considered as a marker of severe bacterial and parasitic infection. However, PCT should not be considered as the only marker we can rely upon in diagnosing of sepsis. The levels of PCT correlate with levels of TNF and IL-6. But the pathophysiological role of PCT in sepsis is not definitely clear yet. The indexes of PCT are most valuable for evaluating treatment efficiency and prognosis.

Maternal deprivation, acute respiratory infections and immune regulation.

OBJECTIVE: The study was designed to investigate the acute respiratory disease incidence (DI) in deprived infants and test the hypothesis if maternal deprivation effects the processes of immunoregulation in infants. METHODS: The prospective study during 1 year in Tbilisi Infant's House was performed. Cohort of 136 infants at age from 1 to 24 months without any congenital abnormalities formed the basic group. The cohort of 136 healthy infants at age 1 to 24 months of the same population living under the maternal care in three shelters of Tbilisi region was randomized as a control. The study included: DI, age of first attack, duration of illness, outcome, plasma immune parameters. RESULTS: The data have demonstrated that maternal deprivation induces a marked increase in the severity of acute respiratory disease among infants. DI was twice as much in deprived children as in control group. Moreover, there was diagnosed the disruption of normal correlations between plasma CD3, CD4 and CD8 in infants under maternal deprivation. CONCLUSION: Maternal deprivation induces changes in processes of immunoregulation in infants resulted in elevation of acute respiratory DI among them.

[Transfer of a child from children's home to family: medical aspects].

The project "Leaving of babies at children's homes and deinstitutionalization" was implemented at the children's home of Tbilisi. The purpose was to find out what influence was produced by deinstitutionalization on the physical and psychomotor development of deprived babies. The study lasted for 12 months. 3 groups of children were investigated. Group 1 comprised children selected for deinstitutionalization, age-matching healthy children who stayed at the children's home were in group 2, and healthy children randomly selected from 2 nurseries of Tbilisi were in group 3. The parameters of anthropometry and psychomotor development were evaluated according to the Denver screening test at the very beginning and in 12 months. The children from the children's home almost caught up, in 12 months after deinstitutionalization, with their control matches. Whereas, the children, who were brought up at the children's home, were behind the group-1 children and controls by all parameters. Projects promoting the upbringing of deprived children in their own or foster families are recommended for implementation.