ANNIVERSARIES
LEAD ARTICLE
REVIEWS
Objective: presenting the latest finding about the process of the formation of the intestinal microbiota of children in the early stages of development and the factors that influence this process.
Intestinal microbiota plays a key role in the physiology and maintenance of the homeostasis of the human body. The results of molecular genetic studies show that the formation of the intestinal microbiota begins in utero, and the child receives mother’s microflora throughout pregnancy, childbirth and breastfeeding. The microbial colonization of a child by mother’s and environmental microorganisms is the most intensive in childbirth and the postnatal period. Both intrauterine and neonatal periods are critical stages in the formation of the child's microbioma, which significantly determine the state of their health throughout further life. The composition of the microbiota being formed depends on the gestational age of the child, the mode of delivery, the type of feeding, antibacterial therapy, the sanitary and hygienic environmental conditions, geographical conditions, etc. A deeper understanding of the processes of intestinal microflora formation will allow developing effective methods for the prevention and correction of microecological disorders in the child.
The review summarizes clinical features, biochemical and molecular-genetic characteristics, laboratory and instrumental indicators, as well as approaches to the treatment of ricket-like diseases: vitamin D-dependent rickets, renal tubular acidosis, de Toni-DebreFanconi syndrome. Differential diagnosis of this disease group is associated with a number of difficulties, the main of which are a fairly low frequency of certain forms occurrence and a strong resemblance with other diseases, that disrupt the metabolism, associated with the influence of many hereditary and external factors. Establishing an accurate diagnosis is important not only for correct and timely treatment, but also for medical-genetic family counseling and genetic risk calculation, since different disease forms have different inheritance types. A competent and timely diagnosis should be based on knowledge of the distinctive features of very similar diseases. The data described in this article can be used by doctors at all stages of the patient survey.
The purpose of the article is increasing awareness of not only neonatologists, but also pediatricians of the discussed problem, assisting patients in all periods of childhood. The article summarizes the up-to-date data on the state of health of children born to mothers suffering from diabetes mellitus of various types, including gestational diabetes. The causes of occurrence of malformations are described, the risk factors for children born with fetopathy are presented. Data are presented on the dynamics of development and manifestation of diseases of various organs and systems in the prospective follow-up from birth to 15 years, which is currently insufficiently focused on. It is concluded that prevention and treatment at the early stages of the disease will not only improve the quality of life of this cohort of children, but also significantly reduce the disability of the entire child population.
ORIGINAL ARTICLES
Ever more children are conceived by extracorporeal fertilization increases every year. The issue of the state of their health vs. their peers born in the same gestational age and with comparable body weight is relevant. Thirty-four children conceived by in vitro fertilization (group 1), and 37 children conceived in the natural cycle (group 2) were compared. The medical history of mothers, the state of health of children in the neonatal period and at a corrected age of 1 year were studied. It is shown that the children from the induced pregnancy are more likely to have infectious diseases in the neonatal period (sepsis, pneumonia, p=0.016, p=0.021). By the corrected age of 1 year, they have a significantly more often a subcompensated form of hydrocephalus and an arrester development rate (p=0.03, p=0.001), which determines the third and fourth groups of health.
The objective of this research was studying the state of newborns born to mothers with various risk factors for hypertensive disorders in dependence of the method of prevention of this pathology. The state of 130 newborns of mothers with risk factors who received various methods of preeclampsia prevention during the gestation was analyzed. In the groups of comparison, pregnancy outcomes, incidence and structure of hypertensive disorders, timing and modes of delivery, as well as the morbidity and mortality rates of newborns, depending on the method of preventive therapy of hypertensive disorders were studied. The Pearson criterion χ2 was used to evaluate the relation between qualitative characteristics. The study found that conventional prevention almost halves the development of hypertensive disorders (p <0.05), the preventive therapy with immune correction developed by us turned out to be 4 times as effective (p <0.01) vs. the pregnant women who did not receive any preventive treatment. The proposed method allows preventing severe forms of pathology and complications of pregnancy, such as intrauterine growth retardation and antenatal foetal death. The incidence of birth of premature infants decreased by a factor of 3.3 vs. the patients without treatment and by a factor of 3 vs. the pregnant women who received conventional methods of prevention. The indicators of the total morbidity of newborns decreased by a factor of 1.5 in the group with conventional treatment vs. the pregnant women without any treatment and by a factor of 3 in the group receiving prevention using the new method.
The literature data and the finding of our studies on the analysis of the correlation between the level of parathyroid hormone and supply of vitamin D of children (n=107) of early age are presented in the article.
The serum level of vitamin D in the analyzed group of children was 24.8 [17.6–32.5] ng/ml, the median of the parathyroid hormone was 21.0 [12.3–25.5] pg/ml. It has been established that children with optimal supply of vitamin D have significantly lower parathyroid hormone levels vs. the children with vitamin D insufficiency (25 (OH) D from 20 to 30 ng/ml) and deficiency (calcidiol values below 20 ng/ml). The correlation between the level of vitamin D and parathyroid hormone was r=-0.18, p=0.035.
The best supply of vitamin D was found in children of the first year of life – 25 (OH) D concentration was 29.95 [16.2–40.3] ng/ml. The parathyroid hormone level (16.5 [10.7–23.8] pg/ml) in these children was reliably lower (p=0.05) vs. the children of the second and third years of life. A positive correlation was established between the age of patients and the parathyroid hormone level (r=0.2, p=0.05). Preventive doses of vitamin D were received by 42.1% of children. The blood serum concentration of 25 (OH) D in them was higher (32.7 ng/ml), and the parathyroid hormone level was significantly lower (14.9 pg/ml) vs. the children who did not receive cholecalciferol preparations (p<0.05).
The obtained results demonstrate a strong correlation between vitamin D deficiency and the increased parathyroid hormone level that reflect the importance of these hormones in the regulation of calcium-phosphorus metabolism and the opposite role in bone tissue calcification.
The role of herpes virus (cytomegalovirus, Epstein-Barr virus) infections in the formation of inflammatory process, as well as in the mechanisms of development of the pathological process in children with juvenile rheumatoid arthritis was shown in the article based on the finding of their our studies.
Objective of the study: optimization of the therapeutic tactics by determining the role of herpes virus infections in the pathogenesis of juvenile rheumatoid arthritis in children.
Viral and bacterial antigens were studied using the immune enzyme analysis and the polymerase chain reaction in 86 children with juvenile rheumatoid arthritis aged 3 to 15 years (mean age of onset of the disease – 4.6 ± 0.7 years, average duration – 2.8 ± 0.4 years).
Results. It is shown that infections caused by herpes virus are the most significant for juvenile rheumatoid arthritis. The obtained data suggest that these infections serve not only as the factors provoking the disease debut, but also are one of the pathogenetic links in the development of the pathological process.
Obesity and closely associated metabolic syndrome develop under the influence of a combination of genetic and environmental factors and are a challenging problem in the present-day pediatrics.
Objective of the study: determination of the significant risk factors causing the formation of metabolic syndrome in childhood and their ranking according to the degree of etiological conditionality and manageability. 483 children aged 5–16 years were examined: 237 children who had metabolic syndrome, 246 children who did not. The complex study included a number of clinical laboratory and instrumental methods of study performed using the conventional methods. Methods of epidemiological statistics were used to calculate the relative (RR) and attributive (AR) risks, as well as the etiological fraction of relative risk (EF).
Results. It has been established that risk factors for the development of metabolic syndrome with a very high and high degree of etiological conditionality which are difficult to control include abdominal (visceral) type of obesity, hyperglycemia, hypertriglyceridemia, those which are averagely difficult to control – lowering of high density lipoprotein cholesterol, hyperuricemia, and the controlled (conditionally controlled) factors include the body mass index more than 30 kg/m2, the duration of obesity of 5 and more years, the birth weight less than 2500 g, hepatobiliary disorders (non-alcoholic liver disease, biliary sludge, gallbladder cholesterosis), eating disorders in the form of a “night eating syndrome”, obesity either in the mother or both parents, mother’s or maternal grandmother’s type 2 diabetes. It has been proven that the timely initiation of therapy and prophylactic measures at the early stages of the disease, contributing to a reduction of the obesity degree and duration of the disease, allows to reduce the risk of forming metabolic syndrome in a child by 23%, improving maternal health and normalizing the body weight during the planning of pregnancy – by 22%.
Conclusions. The analysis of genetic, physiological and social and economic factors enables assessing their contribution to the formation of metabolic syndrome and to classify the risk groups for its development. After classification of risk factors according to the degree of control the researchers can focus on a group of controlled factors and choose the most effective algorithms of therapeutic and preventive measures.
Objective of the study: study of the influence of unfavourable environmental factors on the prevalence and structure of diseases of the digestive system in children and adolescents of the Krasnodar Territory. We examined 9,020 children aged 1–18 in 47 districts and towns of the Krasnodar Territory during the specialized medical examinations. Diseases of the digestive system were diagnosed in 2,454 individuals. Medical history of children was studied, blood, urine, faeces, laboratory and functional tests were analyzed. The environmental state of all territories of the region was studied using the method proposed by the author. The influence of man-caused atmospheric emissions, pesticides introduced into the soil and untreated wastewater discharged into water bodies on the prevalence of diseases of the digestive system and structure, depending on age and sex was assessed.
Results. Epidemiological indicators of diseases of the digestive system in children and adolescents were studied in 47 administrative territories of the region, divided into three zones with different levels of environmental pollution. It is established that the degree of environmental pollution, determined using the integral index of environmental pollution, significantly influences the prevalence of gastroenterological pathology and its structure. Age and sexual dependence of the prevalence of diseases of the digestive tract in the environmentally favourable, conditionally favourable and unfavourable territories of residence was determined.
Sixty-nine children with demyelinating diseases of CNS aged from 5 to 17 years were examined. Etiological diagnostics was performed using the polymerase chain reaction, immune cytochemistry and enzyme immunoassay techniques. The brain and spinal cord magnetic resonance imaging (MRI) was performed, and desquamated circulating endotheliocytes and D-dimer levels in blood were determined on the day of admission to the hospital, on the 30th day, in 3 and 6 months. Significantly higher desquamated circulating endotheliocytes and D-dimer levels were established during the acute course of demyelinating diseases of the central nervous system vs. the prolonged and especially chronic one. Pathogens were detected in 87% of patients: in the form of either mono (in 58%) or mixed infections (in 42% of cases). It was found that if viruses are isolated in blood and/or cerebrospinal fluid after therapy in 3 and 6 months, the desquamated circulating endotheliocyte level remains elevated in patients, and with negative results, desquamated circulating endotheliocytes and D-dimer levels are normalized. The highest D-dimer values are observed in patients with hemorrhagic inflammatory sites on MRI, and significantly higher mean values of desquamated circulating endotheliocytes are found in patients with multiple contrasting foci on MRI scans. It is assumed that the main target in children with demyelinating CNS diseases are cerebral venules, the lesion of which is interrelated with the course of the infectious process of herpes virus aetiology in 80% of cases.
DISCUSSIN
The article discusses the issues of increased meteosensitivity in children and adolescents. Its incidence together with various diseases is given. Over the past 25 years, increased meteosensitivity in children with chronic diseases of the upper digestive tract (gastroduodenitis, peptic ulcer disease) and in children with allergic diseases (atopic dermatitis, bronchial asthma) has been becoming more common. The main syndromes and symptoms that occur with specific and nonspecific responses of the body to unfavourable weather conditions are described. The problems of diagnosis and prevention of pathological meteotropic conditions, including measures of specific and nonspecific effects, are discussed. Simulation of the conditions typical for controlled sub-threshold atmospheric pressure fluctuations in the atmospheric pressure training regime is efficient for children with increased meteosensitivity in order to prevent pathological meteotropic responses.
SHARING EXPERIENCES
Drug-induced liver injury is a disease that occurs during the administration of medications, which is controlled or has a positive dynamics after the drug administration is discontinued, and the renewed prescription of which causes a relapse of clinical and laboratory signs of liver injury. No unified diagnostic criteria have been developed yet. We used the following diagnosis criteria: any excess of the levels of total bilirubin, direct bilirubin, transaminases; temporary association with administration of medications; ruling out other causes of liver injury.
Results. 114 children with tuberculosis, aged 3 to 14, were examined. Drug-induced liver injury during the anti-TB therapy was diagnosed in 77 (67.5%) children. In almost half of the cases (37 children, 48%), the liver injury was asymptomatic and was diagnosed with a biochemical blood test. The most common clinical manifestation of pathology include dyspeptic syndrome (in 42.9% of children), less frequent one is abdominal pain syndrome (in 29.9%). The most common biochemical variant of drug-induced liver injury (in 64% of children) was a mixed variant (increased levels of transaminases and bilirubin). Also cytolytic syndrome was pronounced in 54% (in 31 of 57 children) of cases.
Conclusions. Drug-induced liver injury during the administration of potentially hepatotoxic drugs should be actively detected by a control biochemical blood test every 2 weeks. Early detection of minimal clinical and laboratory symptoms of liver injury in patients with tuberculosis and timely initiation of treatment will allow controlling quickly liver injury, reducing the number of cases of cancellation of TB treatment, improving the outcome and prognosis for both tuberculosis and hepatic conditions.
CLINICAL OBSERVATIONS
The article describes the clinical case of subacute myocarditis in a child with an outcome in dilated cardiomyopathy, complicated with congestive heart failure. Difficulties in diagnosing the disease that manifested with cardiac arrhythmia are discussed. The main signs suggesting postmiocardic cardiomyopathy included a reduced deflection voltage and frequent ventricular extrasystoles with episodes of the ventricular tachycardia in the onset of the disease, left ventricular dilatation, a significant decrease in ejection fraction, increased activity of natriuretic peptide, findings of perfusion scintigraphy and magnetic resonance imaging. Medical therapy and implantation of a cardioverter defibrillator were ineffective. The child repeatedly suffered from syncopal conditions with circulatory arrest, which required resuscitation. Due to the ineffectiveness of drug therapy conducted in the leading federal centres, considering cardiac transplantation abroad was recommended.
Bartonelloses are a group of human diseases caused by gram-negative, aerobic, facultative intracellular bacteria, which only grow in the presence of blood or erythrocyte cleavage products. The diseases are characterized with multiple forms of clinical manifestations due to by systemic damage to internal organs. The clinical case presented by the authors demonstrates the difficulties of the bartonellosis diagnosis in children. The purpose of the demonstration is making aware of the problem of bartonellosis not only specialists in infectious diseases, but also pediatricians. It should be kept in mind that any atypical manifestation of the disease is the reason to rule out infectious pathology. In view of high prevalence of Bartonella among both domestic and wild animals, general immunodeficiency of the population, an increase in the number of HIV-infected patients, an unfavourable environmental and migration situation, the problem of Bartonellosis acquires great social importance for the population of Russia.
GUIDELINES FOR THE PRACTITIONER
The issues of possible correlation between the development of obesity and the state of the intestinal microbiota in children are discussed, and the ways of preventing obesity by correcting the intestinal microflora using probiotics are studied in the article. Information on new types of complementary dairy products containing probiotic microorganisms as well as the data on their use in children of the first year of life is given. The findings of clinical studies of products containing L. rhamnosus GG and BB12 probiotics in children are presented.
Although bronchial asthma is a widespread disease in pediatric population, physicians still face difficulties in early diagnostics of bronchial asthma in preschool children due to a high frequency of bronchial obstruction in this age group. This article covers key points of the resolution adopted by the Panel of Experts of Pediatric Respiratory Society regarding standardization of the approach to diagnostics and therapy of broncho-obstructive conditions, considering a cause of the disease, child’s age and condition severity, as well as a place of nebulized budesonide suspension in maintenance treatment of bronchial asthma and acute exacerbations therapy.
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