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The aim of the work was a comprehensive assessment of the cytokine system and peripheral blood osteocalcin with the establishment of features of their interconnections in children with congenital cleft lip and palate (CCLP) in comparison with corresponding controls at different age periods. Levels of IL17, IL4, IL6, IL1β, IFNγ and osteocalcin were analyzed by enzyme immunoassay in the peripheral blood of 80 children (0–12 months, 1–3 years, 4–9 years, 10–15 years) with CCLP and age-appropriate control of healthy individuals (40 people). An analysis of the obtained data shows that in children with CCLP we revealed significant differences between pro-inflammatory (IL1β, IL6, IL17), regulatory (IFNγ), anti-inflammatory (IL4) cytokines and osteocalcin compared with controls. Differences were found in the content of IL17, IFNγ, IL4 and osteocalcin in healthy children and in children with CCLP in postnatal ontogenesis. Cytokine deregulation of immunosteogenesis in CCLP, leading to a significant deficit of osteocalcin in the first year of life due to imbalance of the cytokine profile: discordant IL17, IFNγ and IL4 were detected. Obtained data are undoubtedly important in the future for developing new strategies for targeted therapy aimed at normalizing osteocalcin levels at different age periods in children with CCLP.

Congenital cleft lip and palate is one of the most common congenital anomalies in children. It has significant medical and social influence on the self-realization of these patients in society. This review of various researches' results from different countries and territories of the Russian Federation (according to the MEDLINE and eLIBRARY.ru databases) provides information on prevalence rate of this pathology among children of our country and worldwide. The role of medical care organization remains unknown among all the presented results of the studies about the role of risk factors of congenital cleft lip and palate development (such as: inheritance, lifestyle, environment).

It is known that children with congenital cleft lip and palate are suffering from recurrent respiratory infections, which worsen the state of their health, and also complicate the results of reconstructive surgical treatment. The aim of the study was to detect defects of mucosal immunity in children with congenital cleft lip and palate, suffering from recurrent respiratory infections, and to create the program of local interferon corrective therapy with an assessment of its effectiveness. The studies included 56 children from the age of 1 to 3 years. Three groups of children were formed: group 1 – 26 children with congenital cleft lip and palate (antibiotic therapy); group 2 — 30 children with congenital cleft lip and palate (antibiotic therapy + local interferon therapy), group 3 — the control group. The clinical examination included a medical history, an assessment of the symptoms of recurrent episodes of acute respiratory infections and exacerbations of chronic infections. Microbiological studies were performed using standard methods. The status of local immunity was detected: the concentrations of secretory IgA, cytokines IL-17, IL-4, IL-6, IL-1β, IFNγ in the oral fluid were tested by ELISA. Results of the study established that in group 1 and group 2 clinical criteria of immunodeficiency with an infectious syndrome were revealed: repeated acute respiratory viral infections from 10 or more times a year, complicated by frequent exacerbations of chronic bacterial infection (up to 10 or more per year). Assessment of the state of local immunity in children with congenital cleft lip and palate revealed a lack of sIgA compared with the control group. Before treatment in group 2 oral fluid level of IL-17, IL-6 were statistically significant increase (p < 0.05); the results of the study also established increase in the level of IL-1β and a decrease in anti-inflammatory IL-4 and regulatory IFNγ relative to the control group (p > 0.05). After complex treatment with the inclusion of local interferon therapy in group 2 the appearance of sIgA, increase in the concentration of IL-4, IL-1β and a decrease IL-17 in oral fluid were observed (p > 0.05). The concentrations of IL-6, IFNγ did not change (p > 0.05). After treatment in group 2 there were a decrease in exacerbations of chronic upper respiratory tract infection and in frequency of acute respiratory viral infections compared with group 1 (p < 0.05). Positive clinical efficacy of local interferon therapy (the gel of recombinant IFNα2b in combination with oxidants — Viferon gel) in the process of staged rehabilitation of children with congenital cleft lip and palate has a protective clinical effect in reducing the frequency of acute respiratory viral infections, reducing the number of postoperative complications, reducing hospital stay, duration of antibacterial therapy and the number of exacerbations of chronic bacterial infection.

The problem of rehabilitation of children with congenital cleft lip and palate (CCLP) is a difficult task and doesn’t lose its relevance. Children with CCLP often suffer from repeated acute viral and bacterial infections of the respiratory tract and upper respiratory tract, which leads to a forced delay in surgical, orthodontic treatment, adequate speech therapy and complications after staged surgical operations. The development of inflammatory processes in children with CCLP is associated with anatomical and topographic features that facilitate the penetration of pathogenic microflora in oral and nose mucosa and, consequently, negative changes in the immune system (IS). The key cells of IS in maintaining homeostasis and ensuring oral health are neutrophil granulocytes (NG). NG dysfunctions in CCLP interfere with the elimination of pathogens and support their persistence. This can occur against the background of previously existing defects in the functioning of the NG system and is aggravated by the significant pathogenicity and massiveness of the impact of various infectious agents. Full diagnostics of NG dysfunctions is necessary for the further implementation of their timely immune correction and prevention of the development of pathological chronic inflammation in response to the pathogenic microflora long-term on the mucous membrane of the mouth and nose. For this purpose study was conducted of the functional activity and phenotypic characteristics of NG in children with CCLP at different stages of complex rehabilitation. Blood samples of 56 children with CCLP 1-3 years (n = 20, group 1), 4-6 years (n = 20, group 2), and 7-12 years (n = 20, group 3) at different stages of complex rehabilitation and 30 conditionally healthy children (control groups) of the corresponding age was studied. A violation of the microbiocenosis of the mucous membranes of the oral and nasal cavities was revealed, which may be a cause or a consequence of a decrease in antibacterial immunity, first of all NG dysfunctions. Common for all age groups children with CCLP NG dysfunction was found: the appearance of NG expressing CD14 receptors that are absent in children of all three control groups, which indicates the presence of viral and bacterial load; defects of phagocytosis associated with a decrease in the number of actively phagocytic NG, impaired NG capture functions; impaired NADPH oxidase release with partial or complete blockade of the response to additional antigenic load, even in the absence of acute clinical manifestations. Comparative analysis of the studied indicators of the expression level of the receptors CD64, CD16, CD32, CD14 NG in children with CCLP demonstrates different equipment, which determines the inconsistency of the phagocytic and microbicidal function of NG in different age periods. Thus, an increase in the expression of these membrane markers, especially CD64 and CD14, in older age groups is accompanied by more significant defects in phagocytic and killing functions of NG, which is associated not only with recurrent viral respiratory infections, but also with a high frequency of associated bacterial infections of the respiratory system and ENT – organs. Revealed NG dysfunctions in children with CCLP of various age groups indicate their inability to implement adequate anti-infective protection, which can lead to atypically occurring viral – bacterial infections and the occurrence of various, including purulent complications in the postoperative period, which requires the development of targeted immunotherapy, included in the program of comprehensive rehabilitation in children with CCLP and aimed at restoring impaired NG functions.

Difficulty in nasal breathing is the most common complaint of children with ССLP. The feeling of difficulty in nasal breathing is subjective and depends on many causes and characteristics of the child’s body. Despite the continuous improvement of diagnostic methods, the problem of evaluating the functions of the nasal cavity remains relevant. Modern computer technology contributes to the emergence of new non-invasive, atraumatic methods that safely evaluate the function of the nose. These methods include anterior active rhinomanometry – PARM. Purpose of the study. To determine the peculiarities of these PARM in children with ARH, depending on the forms of secondary and residual deformities of the nose after cheiloplasty and NGN after uranoplasty. The study involved 59 children with CCLP who were under observation at the Department of Pediatric Maxillofacial Surgery at the TGSI Clinic, which underwent cheilo- and uranoplasty. All patients, depending on the shape and localization of the deformation, were divided into two main and control groups: 1 group comprised 31 patients with secondary and residual deformities of the nose after cheiloplasty, 2 group consisted of 28 patients with secondary and residual deformities of the palate after uranoplasty; 3 group – control included 21 healthy children. The use of computer rhinomanometry – PARM in patients with ARH helps to more reliably determine the presence and degree of nasal obstruction, as well as to control it in the dynamics of the treatment process.

Treatment and rehabilitation of children with cleft lip and palate, who suffered from acute recurrent viral and bacterial respiratory tract and ENT-organs infections is one of the most complicated tasks. The local therapy by interferon was used both before and after surgical treatment: lubrication of the nasal passages and oral mucosa were carried out during 40 days ( 10 days before and 30days after surgical treatment). The priority in treating children with such diseases is given to the gradually increasing efficacy of rehabilitation and lowering post-operative complications and restoring the immune system functional activity.

Today, congenital cleft lip and palate (CCLP) is the most common congenital malformation of the maxillofacial area. According to different authors, the incidence of the defect among infants is 1 per 500--1000 depending on the region. In most cases, CCUPP is not difficult to diagnose; it is detected in the maternity hospital, and child with its parents is sent to a specialized institution for surgical treatment. However, there is a type of isolated cleft palate which may be very difficult to diagnose due to absence of evident defect of the palate. This is hidden (submucosal) congenital cleft palate. [1, 7].

The authors describe a history case of severe congenital dentofacial anomaly with congenital cleft lip, palate and alveolar ridge, associated with somatic disease. The diagnosis was confirmed histologically. The surgical treatment was performed after the careful presurgical preparation due to severe general condition of the child. The indication to the surgical treatment was a significant enlargement of the tumor mass since the child’s birth. The tumor filled the oral cavity and blocked oropharynx almost completely.