Since the term “anaphylaxis” has been invented, there are multiple changes in the views on both pathophysiology and the diagnostic and therapeutic aspects of this disease. There have been currently adopted a number of international documents containing principles of anaphylaxis verification and treatment. However, the experts’ views differ, and some disagreements and problems of anaphylactic reactions remain relevant, especially in pediatric patients. The article discusses current issues and possible ways of treatment of anaphylaxis in children.

The article analyses the data published from January 2020 to April 25, 2020 in the print media or available on the official websites of peer-reviewed medical sources (pre print), international and national medical professional communities, and state regulatory authorities dedicated to the epidemiological and clinical laboratory features of the new coronavirus infection in newborns, infants and older children. The authors have concluded that currently there are no convincing data on vertical transmission of infection. At the same time, they have found that there is a risk of horizontal infection of a newborn child; therefore, there is the need for strict adherence to the recommended algorithms for monitoring children in the neonatal period born by the women with positive or presumably positive COVID-19 (Coronavirus disease 2019) status. The authors note that due to the limited quantity of observation cases, all existing recommendations are temporary and may be revised. The newborns from mothers with COVID-19 demonstrate the variability of clinical picture from asymptomatic course to severe respiratory failure. In the post-neonatal period children have asymptomatic or mild course of a new coronavirus infection. The authors note that some children with an asymptomatic course of the disease have pneumonia detectable during X-ray examination. Children with the manifest forms of COVID-19 do not have specific clinical symptoms; both children and adults have fever, cough and other catarrhal symptoms; tachypia, tachycardia and gastrointestinal symptoms are much less common. It has been found that children with COVID-19, unlike adults, are unlikely to develop severe pneumonia, as well as conditions requiring intensive care and mechanical ventilation. Changes in laboratory parameters in children also do not have a consistent pattern and they are less pronounced than in adults. The epidemiological data indicate that children are one of the main sources of the ongoing spread of infection in the human population. The authors present the first-ever data on the cases of 45 infants born from the mothers with positive COVID-19 status in Moscow.

The first principles and fundamental elements of perinatal regionalization were formulated more than 40 years ago. Over the past years this organizational model was substantially complicated and modernized. Numerous large, population-based studies describe and analyze the effects of perinatal regionalization, propose and study the possible directions of its development. It has been proven that the bed capacity of the obstetric hospital and the flow of extremely premature newborns in the hospital largely determine the outcome of the premature newborn, morbidity, mortality, long-term results, affecting important population indicators, neonatal and infant mortality. The review summarizes the data on available population studies, outlines the basic principles of the formation and development of the perinatal regionalization system.

This review presents the theoretical, practical and geographical aspects of Rett syndrome and other rare diseases, according to the data of the last VIII International Congress in Russia, and the main publications on Rett syndrome. The issues highlighted by the participants remain relevant and determine the direction of modern studies. The presentations made at the symposium helped to form a global concept of the molecular and cellular mechanisms of Rett syndrome and a number of rare genetic/genomic diseases. The article presents a number of domestic findings in the field of Rett syndrome and other rare diseases. The authors also present information on rare diseases associated with the Rett-like-phenotype or with mutations/variations of the MECP2 gene sequence copies. The authors consider the identified chromosomal (genomic) disorders / diseases in the context of rare diseases. This approach to the Rett syndrome studies analysis is quite new in the world research practice. We hope this review to become valuable not only for specialists in the field of rare genetic diseases, but also for the scientists and clinicians studying Rett syndrome and for physicians (pediatricians, geneticists, neurologists, psychiatrists) meeting these patients in their practice.

The article reviews publications on genetically determined vesicoureteral reflux and reflux nephropathy, accompanying certain phenotypes of systemic or local forms of hereditary connective tissue dysplasia (Ehlers–Danlo, Marfan, Williams syndromes, sluggish skin). The authors determined the role of mutations of the genes of fibrillar collagen, elastin, transforming growth factor β1, tenascin, lysyl peroxidase, metalloproteinases and other components of connective tissue, as well as their possible combination in the development of pathology. The authors call the specialists to continue research on genetic mutations in vesicoureteral reflux and reflux nephropathy.

The article presents data on the study of gene interconnections between the xenobiotics detoxification genes in various phases.

Materials and methods. The study involves 131 children with congenital heart diseases (CHD) and 103 conditionally healthy children. The genotyping was performed by RT-PCR method using TaqMan probes. Intergenic bonds were analyzed via MDR v.3.0.2.

Results and conclusion. We discovered no statistically significant differences in the genotype distribution in children with CHD and conditionally healthy donors. The analysis of intergenic interactions helped to develop a five-locus model characterized by the highest reproducibility, sensitivity and specificity: GSTP1 rs1793068 – GSTP1 rs6591256 – GSTP1 rs1871042 – CYP1A1 rs1048943 – CYP1A2 rs762551. This model was used to determine a number of protective and risky combinations of congenital heart defects-associated genotypes in children.

Diagnostics of Iron deficiency anemia (IDA) in outpatient pediatric practice is often based on decreased hemoglobin level. Latent iron deficiency diagnostic is not a part of current routine practice.

Objective. To study the diagnostic value of red blood cell indices and reticulocyte hemoglobin equivalent in diagnostics of iron deficiency in full-term infants.

Children characteristics and research methods. A prospective cohort study of healthy full-term children aged from 6 to 12 months at the children hospitals of Samara and Tolyatti. The laboratory examination included a general blood test to determine the concentration of hemoglobin, the number of red blood cells, red blood cell indices, and reticulocyte hemoglobin equivalent (Ret-He); to determine serum ferritin and C-reactive protein. The AUC (area under the curve) was used to determine the diagnostic value of quantitative indicators. The children with anemia without iron deficiency and children who received iron supplements within 1 month prior to laboratory examination were excluded from the analysis.

Results. The study involved 207 children. When diagnosing iron deficiency in children, the highest AUC was found in Ret-He: 0.747 [0.679; 0.816] in 6-months-old children and 0.790 [0.708; 0.871] in 1-year-old children. The Ret-He diagnostic value was higher in children with iron deficiency: AUC 0.826 [0.754; 0.898] in 6- months-old children and 0.865 [0.809; 0.920] in 1-year-old children.

Conclusion. Ret-He is a better predictor of iron deficiency in children under 1 year as compared to the red blood cell indices. The diagnostic value of red blood cell indices and Ret-He is higher in case of iron deficiency anemia than in case of iron deficiency conditions.

The article presents research methods to detect the frequency of diagnostic errors.

Objective: to compare clinical and pathological diagnoses in order to determine the frequency, causes and ways of avoiding diagnostic errors in children with infectious pathology specific to the perinatal period. The authors studied 234 death cases in the intensive care unit for newborns in 2006–2018, and they found diagnostic errors in 18,3% of cases. 53,4% of the diagnostic errors were associated with unrecognized infectious diseases specific to the perinatal period. The authors found that the correct intravital diagnosis was impossible for objective reasons in 65% of cases. Those objective reasons were mainly caused by diagnostic difficulties due to the lack of characteristic clinical data or the atypical course. Almost in every third patient the diagnostic errors were caused by subjective reasons and were associated with the diagnosis of congenital cytomegalovirus infection and neonatal sepsis. The subjective errors were often caused by the so-called doctor’s bona fide delusion due to a lack of knowledge, skills, experience. As the judgment error was the most common reason for misdiagnosis we need to improve the clinicians’ cognitive condition. Based on the audit results, the authors proposed the additional diagnostic approaches for certain diseases. One way to reduce errors is to improve educational initiatives for doctors.

The authors present the reference values of the major respiratory events based on polysomnographic evaluation of 2,073 sleeping infants of the first year of life. These reference values were developed in accordance with the adopted LMS (lambda-mu-sigma) algorithm aimed at smoothing and maximal approximation of the calculated values to the real ones. The article describes the centile curves and centile tables of the respiratory events indices, maximal lengths and densities of the different types of apneas, periodic breathing, oxygen saturation and de-saturation indices at different sleep stages of the 1-to-52-week-old infants. The reference values are compared with available literature data.

Relevance. The study of the etiological structure, clinical features of congenital infections and the immune status of children with perinatal HIV contact will help to improve the program for the diagnosis, treatment and prevention of these diseases.

Objective. To characterize the clinical features of congenital infections and changes in the immune system in children with perinatal HIV contact, taking into account their HIV status.

Methods. A clinical, serological, molecular genetic, cytological, immunological examination of 203 children with perinatal HIV contact, including 91 HIV-positive patients and 112 HIV-negative patients.

Results. Congenital infections were diagnosed in 43.3% of children with perinatal HIV contact. They were characterized by a predominance of cytomegalovirus (30%) and Chlamydia trachomatis (14.3%) in the etiological structure; those infections proceeded as a mono-infection (61.4%) or in a localized form (52.5%). In the group of HIV-positive children, congenital infections developed in 68.1% of patients. In most cases congenital infections were caused by cytomegalovirus (45.1%), herpes simplex virus (6.6%) and bacteria (11%); they proceeded as an associated infection (46.8%), and in a clinically manifest localized (61.3%) and generalized forms (33.9%). The clinical features of congenital infections in HIV-infected children were associated with more significant disorders in the immune system, especially in T-cell link.

Conclusion. The revealed clinical and immunological features of congenital infections in children with perinatal HIV contact must be considered during diagnostic, therapeutic and preventive procedures.

The article presents a comparative analysis of the cytokine network in 161 patients with pertussis under the age of 1 year and in 180 patients over the age of 1 year. The studies revealed lower production of immunoregulatory cytokines (interferon-γ and interleukin-2) in patients under the age of 1 year at all stages of the disease and with all variants of pertussis (both mono- and mixed infections). The researchers revealed the relationship between the level of interferon-γ production and the severity of pertussis. They revealed age differences in the interferon-8 production in patients with mixed infection, which can determine clinical features and cause bronchopulmonary complications. The authors demonstrated the features of the dynamics of spontaneous and induced production of interleukin-6 and anti-inflammatory cytokines (interleukin-4, interleukin-10) in children under the age of 1 year; these features can be considered as immunological markers determining the imperfection of the humoral response in patients with pertussis in this age group.

Objective. To study the risk factors of noncommunicable disease spread in adolescents based on the mass pole results.

Methods. The authors conducted four waves of study within the framework of the monitoring project “Risk factors for human health” in 2014–2017. The study included a multistage stratified territorial random sample of 1,691 patients over 11 years. The research population included 170 adolescents (11–19 years) (10%).

Results. An adverse profile of risk factors for noncommunicable diseases was predetermined by: overweight in adolescents (10%), increased blood pressure (18%), unfavorable history of cardiovascular events in close relatives (60–70%), nutritional disorders (80–96%) , low level of physical activity (5%), smoking (20%), and alcohol consumption (26% of respondents). The body weight deficiency (35%) and overweight (10%), along with sufficient consumption of fresh vegetables and fruits in only 7% of cases reflects gross malnutrition of adolescents, which determines their future development. Awareness of adolescents of the main risk factors for noncommunicable diseases remains low (less than 30–40% for different factors). The example of close relatives, friends and stressful situations predetermine the emergence of bad habits (consumption of alcohol and tobacco) in adolescents.

Scope of application. Pediatrics, public health, epidemiology.

Conclusion. In order to correct adverse risk factors of noncommunicable diseases, it is necessary to attract a wide range of specialists, including intensive family and personal psychological consultations with adolescents. These measures will motivate adolescents to a healthy lifestyle and reduce the burden of noncommunicable diseases in the population of the Russian Federation.

The children’s health condition in the Russian Federation, including adolescents, has been characterized by negative trends in the past thirty years.

Objective. To identify the main trends in sickness rate (both total and registered for the first time) in 15–17-year-old girls in the Russian Federation, as well as to track the quantity and dynamics of chronicity of diseases by classes and types.

Material and methods. The authors analyzed the data of form №12 of the federal statistics in 2000–2017 using the descriptive statistics method.

Results. The researchers revealed a significant increase both in the total sickness rate from 1613,8 to 2532,5 per 1,000 girls (by 56,9%) and in the sickness rate registered for the first time from 967,5 to 1577,3 per 1,000 girls (by 63,0%). The increase in total incidence is observed in the most classes of diseases: neoplasms (2,4 times), injuries, poisoning and some other consequences of external causes (2,4 times), congenital anomalies (malformations; 2,3 times), cardiovascular diseases (2 times), diseases of the musculoskeletal system and connective tissue (2 times). Also there was revealed the increase in the incidence registered for the first time in the overwhelming majority of classes of diseases, for example: injuries, poisoning and some other consequences of external causes (2,5 times), diseases of the nervous system (2,2 times), cardiovascular diseases (2 times), neoplasms (2 times), diseases of the ear and mastoid process (2 times), diseases of the musculoskeletal system and connective tissue (1,9 times). High index of the chronicity for all classes of diseases reflect the initially high level of chronic pathology in 15–17-year-old girls, which is an unfavorable characteristic of their health condition. Having analyzed the chronization index the authors revealed its maximum growth for congenital anomalies (malformations; by 31,1%) and neoplasms (by 23,0%), and for certain nosologies: menstrual disorders (5,8 times) and renal failure (4,2 times).

Conclusion. The health of children, and especially adolescents, determines the national health in the nearest future; therefore, its preservation and improvement require thorough attention.

The authors conducted an international multicenter double-blind, placebo-controlled clinical study to obtain additional data on the efficacy and safety of a 12-week course of Anaferon for children for the prevention of acute respiratory viral infections (ARVI), including influenza, in children during the rise in seasonal morbidity (RCT of the Ministry of Health of the Russian Federation: №356 dated June 29, 2017; ClinicalTrials.gov Identifier: NCT03301155).

Materials and methods. The study involved 1,036 children (1 month – 6 years 11 months 29 days) during two epidemiological seasons. The patients were divided into 2 groups: 528 patients received Anaferon for children 1 tablet a day for 12 weeks, 508 patients received placebo according to Anaferon for children scheme. The primary end point was the duration of the period from the first dose of the drug until manifestation of ARVI/influenza. Additional end points were percentage of children not falling with ARVI/influenza during 4-, 8- and 12-week course of preventive therapy; percentage of children with respiratory or ear-nose-throat bacterial infections requiring antibiotics within 12 week; percentage of children hospitalized with ARVI/influenza or their complications within 12 week. To assess safety, the authors analyzed the presence and nature of the adverse events (AEs), their severity, connection with the medication, outcome. The authors used the following statistical methods: calculation of hazard ratio, median time to the manifestation of symptoms of ARVI / influenza, 95% confidence intervals.

Results. The Intention-to-treat (ITT) and Per Protocol [РР] analysis included the data of 1,021 [975] patients: 520 [494] – Anaferon for children group and 501 [481] –Placebo group. The average duration of the period from the first dose of the drug to the development of ARVI/influenza symptoms obtained as a result of the analysis of the statistical model was 428.8 [434.1] days for Anaferon for children group, that is 1.5 times higher than in Placebo group (275.8 [274.9] days; p=0.001 [p=0.0009]). The percentage of children without ARVI/influenza was 99.2% [99.2%] in Anaferon for children group (versus 90.2% [90.0%] in Placebo group; p=0.0003 [p=0.0003]) within 4 weeks, 92.7% [92.3%] (versus 82.8% [82.7%]; p=0.0003 [p=0.0003]) within 8 weeks, and 81.5% [81.8%] (versus 73.4% [73.4%], respectively; p=0.0021 [p=0.0021]). None of the patients was hospitalized for ARVI/influenza or complications. The frequency of AEs in Anaferon for children and Placebo groups had no differ. No one AE definitely related to the study drug was registered.

Conclusion. The results confirm the efficacy and safety of a 12-week course of Anaferon for children to prevent ARVI and influenza during seasonal rise of morbidity in children.

The objective of the article: to demonstrate the peculiarities of tuberculosis in young children and the high probability of the transition of primary tuberculosis in a child from a sociopathic family to a chronic process due to the absence of medical supervision after chemotherapy. The article describes a clinical case demonstrating the influence of dysfunctional social risk factors on the development of chronic primary tuberculosis in a child. The authors provide a detailed information of medical care to the child, including surgery.

Objective: to present a clinical case of spontaneous obliteration of congenital arteriovenous malformation of the brain in a 4-year-old child. Neurosonography revealed arteriovenous malformation in a 1-month-old girl; the diagnosis was confirmed by magnetic resonance imaging and multispiral computed tomography of the brain. The child did not receive surgical and drug treatment. Dynamic observation showed a decrease of malformation, and a control examination (age: 4 years) revealed a focus of gliosis, which indicated a complete spontaneous regression of arteriovenous malformation. The authors discuss diagnostic features, tactics of conservative and surgical treatment of children with arteriovenous malformation.

Objective: to present the evolution and modern concept of pediatric sepsis.

According to many authors, pediatric sepsis is considered to be the main cause of death from infectious diseases; and the mortality is associated with a late diagnosis and non-compliance with treatment guidelines. The article discusses the evolution of views on sepsis over the past 30 years. It analyzes the changes of sepsis concepts in adults from Sepsis-1 to Sepsis-3. Currently, sepsis is considered as a life-threatening organ dysfunction due to dysregulation of the body’s response to infection rather than a progressive systemic inflammation. Since sepsis is based on a pathobiological process, its definitions should be applied both to adults and children. However, the terminology and intensive care of pediatric sepsis is beyond the recommendations of Sepsis-3. Over the last 3 years the scientists have studied various pediatric scales to verify sepsis and introduce the Sepsis-3 ideology into pediatrics. Currently, the consensus and multidisciplinary approach of pediatricians and intensive care physicians is extremely important to achieve real success in early diagnosis and reduce mortality in children with sepsis.

The authors analyzed the results of diagnostics and treatment of arteriovenous malformations of the Galena vein in 6 newborns at the Bashlyaeva Children City Clinical Hospital in 2018–2019. They described the main methods of early and accurate topical diagnosis of the disease, clinical manifestations depending on the size and type of malformation, treatment options and their results in the near future and long-term perspective. The authors have concluded that a multidisciplinary approach involving a resuscitator, cardiologist, neurosurgeon and radiologist plays the most important role in preparing patient for surgery.

The article presents a modern classification of hypertensive crises in children. The authors describe detailed tactics of emergency care of hypertensive crises in children. They consider the treatment of hypertensive crises with beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, alpha blockers. The article contains a table of the main antihypertensive medications used to treat hypertensive crises.

Fever in children is one of the most common reasons for seeking medical care and use of antipyretic drugs. The reasons can be various. It is extremely important for the pediatrician to find the cause of the fever and prescribe adequate therapy. Antipyretic drugs are symptomatic, they only relieve the condition of the child and improve the quality of life. The article reviews national and international studies and clinical guidelines of professional communities on fever in children. Currently, only ibuprofen and paracetamol fully meet the safety and efficacy criteria, and they are recommended for use in pediatric practice as antipyretic drugs.

Lactose (β-galactosyl-1,4 glucose) is milk sugar, the main disaccharide of human and other mammalian breast milk. Lactase is intestinal disaccharidase that catalyzes the lactose hydrolysis. The lactase gene LCT controls biological function of the enzyme. The age-related genetically determined feature of disaccharide expression, epigenetic factors, and natural selection with persistent tolerance to milk sugar throughout lifetime has divided the human population according to the LCT gene into two phenotypes: lactase persistent and lactase non-persistent. There is conflicting evidence that the latter phenotype is associated with low calcium absorption and the development of osteoporosis. The regular use of fermented probiotic dairy products by individuals with the lactase non-persistence phenotype ensures the accumulation of peak bone mineralization and prevents osteoporosis.

The article presents a modern view of amoxicillin in the treatment of acute respiratory infections in children from point of view of a microbiologist and clinical pharmacologist. Modern microbiological methods have changed the idea of the microbiota of the respiratory tract, however, the etiology of acute bacterial infections of the respiratory tract has not undergone significant changes – Streptococcus pneumoniae and Haemophilus influenzae are still the most common pathogens. Amoxicillin remains the drug of choice for most respiratory infections of bacterial etiology. Inhibitor-protected aminopenicillins (amoxicillin/clavulanate etc.) do not have advantages over amoxicillin in most cases of acute respiratory tract infections, but increase the risk of adverse events. Current data on macrolides, which are widely used in clinical practice, indicate the need to limit their use in acute infections of the respiratory tract due to the increase in resistance of S. pneumoniae and the absence of clinically significant activity against H. influenza. Current information on the resistance of S. pneumoniae and H. influenzae, as well as available data on the pharmacokinetics of amoxicillin, require a review of dosing approaches. The daily dose of amoxicillin in children with acute respiratory infections should not be less than 45–60 mg/kg, and in many cases (acute otitis media, infections caused by H. influenzae or penicillin-resistant S. pneumoniae strains), more than 90 mg/kg/day is required. Amoxicillin has a wide therapeutic range, and therefore the use of high doses of the drug is not associated with a decrease in the safety of therapy.