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Журнал "Здоров`я дитини" (62) 2015. Тематический выпуск "Детская гастроэнтерология"

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Analysis of functional gastrointestinal tract in children with bronchopulmonary dysplasia

Автори: Senatorova G.S., Chernenko L.M., Muratov G.R., Bashkirova N.V. — Kharkiv National Medical University

Рубрики: Педіатрія/Неонатологія

Розділи: Клінічні дослідження

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The Concept of the State Program "Healthy Child for 2008-2017" notes that the health of children is a priority of the Ukrainian state policy and modern society. However, despite the rapid introduction of new technologies in neonatology, neonatal mortality rates in Ukraine have not diminished. In many countries, increase in the proportion of preterm birth is observed against a background of demographic crisis and deterioration of reproductive and somatic health. This again emphasizes the need for careful research from the perspective of evidence-based medicine and implementation of the results in health care establishments providing medical care for children from the group of high risk of death or forming a stable combined organic pathology of various organs and systems. Therefore, reducing infant mortality is one of the most important tasks of Ukrainian pediatrics. Of the causes of death of children under 1 year of age, 70% depend on maternal health and access to and quality of health care for women during pregnancy, childbirth and children in the neonatal period.  Main problems that occur in children in the neonatal period are hypoxia, respiratory disorders, hypothermia, intraventricular hemorrhage, sepsis, intrauterine infections and others. These conditions result in overstrain of immature non-specific adaptive mechanisms, which was described in 1936 by Hans Selie. Despite the increase in the absolute number of children surviving in intensive care units for newborns over the recent decades, nearly 50% of preterm infants are at risk of chronic disease and disability.
Development of perinatal medicine, the further improvement of methods of care for newborns, respiratory support and intensive care, the use of surfactant replacement therapy not only have allowed significant improvement in survival of premature newborns but also have set neonatologists new challenges, including bronchopulmonary dysplasia (BPD), the first  in frequency and clinical significance.
According to many authors, lung maturation and growth of the lungs occur only with adequate nutrition of the child. «Gold standard» is the so-called "nutritional support", the quality of which largely influences the further development, indicators of physical and neuropsychic development of the child.  Even a slight limitation in the supply of basic substances and reduction of caloric intake can lead to retardation in bronchopulmonary system development, double the rate of proteolysis in the lungs.
The aim of the work was to analyze the features of the functional state of the gastrointestinal tract in children with bronchopulmonary dysplasia.
Materials and methods. The study was performed by Pediatrics and Neonatology Department No. 1 of KhNMU (Head of Department doctor of medical science, professor G.S.Senatorova) at Regional Centre for Diagnosis and Treatment of Bronchopulmonary Dysplasia in Children of Kharkiv Regional Children's Hospital (chief doctor – candidate of medical sciences, associate professor G.R. Muratov, director of the center - candidate of medical sciences O.L. Logvinova).
The study involved 83 children aged from 1 month to 3 years with bronchopulmonary dysplasia. BPD diagnosis was made according to the International Classification of Diseases, 10th revision. Informed consent was signed by the parents prior to the study. Evaluation of physical development was carried out using centile graphs. The comparison group included 20 age-matched children who were born prematurely, but later did not have clinical and radiological signs of  BPD and any chronic disease.
Statistical analysis was performed using statistical package «EXCELL FOR WINDOWS» and «STATISTICA 7.0. FOR WINDOWS». Depending on the chosen statistical model both parametric and non-parametric methods were used to test the hypotheses of the work. For samples of distribution that did not comply with Gaussian law, median (Me) and interquartile scope (Lq - lower quartile; Uq - upper quartile) were determined. To compare dispersions, Fisher's criterion (F) was used, comparing sample particles, the method of angular transformation with F-test assessment was used. To determine the association between quality characteristics, Pearson χ2 test (Fisher's exact test in the case of 2x2 tables) was used. The results were considered statistically significant at p <0.05.
Results. Among the examined children of the main group boys prevailed in the number (60.2±5.4% and 39.8±5.4%, respectively; F = 7.01, p<0.01). Group age-dependent patterns in children with BPD agreed with the relevant general trends among the investigated children, namely boys prevailed among the children  both of the first year of life (K = 1.72) and aged 2 - 3 years (K = 1.66 ). The study of the age ratio  in the investigated groups shows that bronchopulmonary dysplasia was most likely under 1 year of life (72.3±4.9%; F = 35.43, p <0.001). Reduction of the relative number of patients with the age is due to the fact that the clinical manifestations of the disease regress during the growth of the child.
Indicators of physical development of children with bronchopulmonary dysplasia are important in assessment of both the severity and prognosis of the disease. The analysis of anthropometric indices revealed that 89.2±3.4% of children with BPD had disharmonious physical development (F = 134.8; p<0.001). Of them, 60.2±5.4% of children (overwhelming majority, F=20.7; p<0.001) had disharmonious physical development due to low or very low body weight; in 3.6 ± 2.1% due to great body length. The physical development of the controls was regarded as harmonic mean in the majority of children (90.0 ± 6.8%). Аnd only in two children as disharmonious due to low body weight.
Objective examination of the digestive system demonstrated in the vast majority of children with BPD (97.6±1.6%; F=263.3, p<0.001) hepatomegaly and in 9 (10.8±3.4%) children splenomegaly. These changes can be related to compensation reaction of the organism to chronic inflammation of the respiratory system. Fifteen (18.1±4.2%) children had predisposition to constipation, most probably of central origin.
Diagnostic measures in children with BPD revealed certain changes in the laboratory findings. The changes in coprogram were detected in the majority of children, i.e.  71 (85.5 ± 3.9%; F = 103.5, p <0.001), of them 45.8% demonstrated undigested or digested fiber, 22.9 %  steatorrhea, 21.7%  amylorrhea, 9.6%  creatorrhea. 
In our study 11 (13.3 ± 3.7%) children had marked increase in β-lipoprotein (62.0 (59.0; 68.0) c. u.), 2 (2.4±1. 6%) children increased cholesterol level (7.6 (7.5; 7.7) mmol/l). Fifteen (18.1±4.2%) children had reduction in β-lipoprotein level (28.0 (23.0. 29.0) c.u.) and 14 (16.9±4.1 %) patients increased cholesterol level (2.545 (2.4; 2.7) mmol/l). The increase in alkaline phosphatase (8400.0 (7600.0. 11000.0) nmol/s*l) was noted in 15 (18.1±4.2%) children. Increased transaminases level was observed in 8 (9.6±3.2%) children, alanine aminotrasferase (0.810 (0.69; 1.04) mmol/l∙h) and aspartate aminotransferase (0.910 (0.560; 1.25) mmol/l∙h) being equally increased. These children were conducted investigation for markers of hepatitis B, C, namely HBsAg. HBcAg. HCV. All results were negative, which allowed to exclude the presence of viral hepatitis. 
Changes in proteinogram were noticed in 37 (44.6±5.4%) children with bronchopulmonary dysplasia. Of them hypoproteinemia was observed in 28.9±5.0% of children, dysproteinemia  in 22.9±4.6% of patients. These changes in children with BPD can be interpreted as the body's response to inflammation or nutritional disorders due to failure in intake of main ingredients or disorders in absorption and digestion functions of the gastrointestinal mucosa.
To clarify these issues tetrachoric indicator was used to analyze the relationship between qualitative criteria: presence or absence of hypoproteinemia and pathological changes in coprogram (amylorrhea. steatorrhea. creatorrhea) in children with BPD. The above calculations led to the conclusion that the level of protein in the serum of children with BPD depends on the digestive function of the gastrointestinal tract (χ2 =4.08; p=0.043), disorders of which may be inherent to preterm infants due to immaturity of enzyme systems the gastrointestinal tract. 
1. The vast majority of children with bronchopulmonary dysplasia (F=20.7; p<0.001) were characterized by disharmonious physical development due to low or very low body weight, which requires increased calorie intake with sufficient protein content.
2. Blood serum protein level of children with bronchopulmonary dysplasia depends on the digestive function of the gastrointestinal tract, the disorders of which are inherent in preterm infants due to immaturity of the enzyme system of the gastrointestinal tract.
Solution of a multifactorial problem of improving the quality of life of children with bronchopulmonary dysplasia is promising, which is possible only if a comprehensive rehabilitation program including organization of early detection and correction of various disorders in postnatal adaptation of preterm infants is created.

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