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Aim. To determine the frequency and factors contributing to the formation of c-ma "hyperechoic pyramids" in children born with very low and extremely low body weight, as well as to assess kidney function in this contingent of children in a three-year catamnesis. Materials and methods. A comparative analysis of the ultrasound pattern of the urinary system was carried out in 756 premature babies, from birth to 3 years of age, two groups were identified: group I – 133 children who had hyperechoic pyramids in the neonatal period; group II – 643 children without hyperechoic pyramids in the neonatal period; group III – the comparison group – 3000 full-term neonates. Results. The symptom of "hyperechoic pyramids" was detected in 15% of premature babies (group I) by the end of 1 month of life (25±6 days), in full-term babies (group III) – in 23 at the age of the first 3–10 days of life. In 2% of premature infants up to 2 months of age, hyperechoic inclusions were diagnosed, giving an acoustic shadow, which were interpreted as kidney concretions. It was revealed that the need (100% vs 71%) and duration (9.7 days vs 2.8 days) for mechanical ventilation, drug load and frequency of artificial feeding (92% vs 19%) in the I group were higher than in the II group. By 12 months of age, signs of nephrocalcinosis with hypercalciuria in group I were detected in 74% of patients and by 36 months were preserved in 23%. In 2% children with renal nodules detected in the first months of life, these changes up to 36 months of life and by 3 years of age, the frequency in group I was 6.6%. Conclusion. In children born with very low and extremely low body weight, there is a high frequency of detection of "hyperechoic pyramids," which tends to decrease with the growth of the child. In some children, the changes are persistent with a risk of progression in the absence of proper observation and treatment. Among the aggravating external influences, a significant role belongs to long-term mechanical ventilation and oxygen dependence, high drug load by various groups of drugs, as well as artificial feeding in neonatal and infancy.

Nowadays, when the number of couples affected by infertility increases significantly, the issue of the use of assisted reproductive technologies (ART) is particularly important. In vitro fertilization (IVF) is the ART that is used most frequently due to its high positive results. Priority status initially was accorded by the researchers to quantitative indicators, and the health of children born as a result of ART was analysed extremely rarely. At the present time, all the risks of using ART are being assessed. Despite the success of the procedure, there are times when children are born prematurely. In Russia, starting from 2012 all children born after 24 weeks of gestation and weighing more than 500 grams are legally regarded as human beings and must be provided with life-saving medical care. Observations show that such children have significant health problems: the most serious damage is caused to the nervous system, respiratory organs, and visual system. The article describes cases of premature IVF babies with critically low birth weight and reviews their further development. Approaches to the management of premature IVF babies should be based on the awareness of the problems of extreme morphofunctional immaturity, individual selection of habilitation programs. Observations should be comprehensive (involving narrow specialists according to indications), which plays an important role in the subsequent development of children. If the management of such babies is arranged properly, their health status improves significantly, and physiological parameters achieve close to “normal” standards.

Значимость особенностей генотипа в исходах тяжелой дыхательной недостаточности у новорожденных с экстремально низкой массой тела пока не ясна. Целью исследования являлась оценка взаимосвязи выживаемости с носительством некоторых генов предрасположенности к адверсивному течению респираторного дистресс - синдрома у новорожденных с экстремально низкой массой тела (ЭНМТ). Методы. Дизайн - контролируемое, проспективное, нерандомизированное, одноцентровое исследование. Критерии включения: новорожденные с ЭНМТ менее 1000 г и гестационным возрастом 28 недель и менее, ИВЛ более 3 суток. Критерии исключения: множественные пороки развития, гестационный возраст менее 26 недель, гибель в первые 48 часов жизни. В разработку включено 88 пациентов. Исследовался полиморфизм генов белка сурфактанта В (SFTPB 1580 C>T), интерлейкина-1β (IL1B 3953 C>T), рецепторного антагониста ИЛ-1 (VNTR полиморфизм интрона 2 IL-1RN), интерлейкина-10 (IL10 627 С>A), фактора некроза опухоли (TNF-α 308 G>A), гена протромбина (F2-20210 G>A), гена 5-го фактора свертывания (Лейдена) (F5-1691 G>A), гена проконвертина (F7-10976 G>A), гена фактора Хагемана (F13), гена фибриногена В (FGB 455), гена интегрина - альфа тромбоцитов (ITGA2 807 C>T), гена бета - субъединицы фибриногена тромбоцитов (ITGB3-1565 T>C), гена ингибитора активации плазминогена 1-го типа (PAI-1 675). Результаты. Полученные данные указывают на отсутствие взаимосвязи между распределением аллелей и генотипов исследуемых генов и выживаемостью пациентов. Заключение. Носительство изученных генов предрасположенности к развитию респираторного дистресс - синдрома новорожденных, инфекционных осложнений и тромбофилии у новорожденных с ЭНМТ не ассоциировано с их выживаемостью в неонатальном периоде.

Introduction. The use of in vitro fertilization methods plays an important role in overcoming the childlessness of families, but they must be combined with the success of nursing premature newborns to increase the effectiveness of assisted reproductive technologies. Children with very or extremely low body weight are at risk of increased rates of infant mortality and disability. The study of the state of health and the analysis of the psychomotor/neurological status of such children is extremely important due to the study of the possibilities of reducing the frequency of negative outcomes.Aim. A study during the first 3 years of neurological/psychomotor development in premature infants diagnosed with extremely low/very low body weight, born as a result of in vitro fertilization and naturally.Materials and methods. Studies of neurological/psychomotor development in premature infants have been carried out. The study included 189 infants diagnosed with prematurity at birth. The studies were carried out on the basis of the intensive care unit and the department of prematurity and neonatal pathology at the Republican Children’s Clinical Hospital (Ufa). Then, for 3 years, regular observation was carried out in the follow-up room in the same institution. Dynamic assessment of neurological and psychomotor status was performed using the Clinical Adaptive Test and Clinical linguistic and auditory milestone scales, as well as Gross Motor testing.Results and discussion. It was found that the incidence of neurological morbidity related to developmental delay is significantly higher in children born as a result of in vitro fertilization than in those conceived naturally. Thus, the number of children lagging behind in speech development at the age of up to 1 year is 59.1/59.6 and 52.1/52.3% when diagnosed with very low and extremely low body weight.Conclusion. The dynamics of the average coefficient of speech development in children conceived artificially did not reach (less than 75) normal values by the age of 3, and in the control group, the coefficient of speech development was normalized. There is no significant difference between very low and extremely low body weight children.

Hyperglycemia in premature newborns is an independent risk factor for death, so blood glucose testing is widely used in the practice of neonatal intensive care units.Objective: to evaluate the associations of the frequency of carriage of allelic variants of polymorphic loci of genes predisposing to type 2 diabetes mellitus in newborns with extremely low body weight and hyperglycemia.Methods. The study design is prospective, controlled, single – center, non-randomized. Genomic DNA samples were studied in newborn infants with extremely low body weight (ELBW) (n = 105). Previously, we compared the distribution of allele frequencies of the studied genes between a group of newborns with ELBW and a population sample of adults (control). Then, the distribution of allele frequencies of the genes was compared depending on the presence of hyperglycemia in newborns with ELBW. For the analysis, loci with already known association with the development of type 2 diabetes mellitus were selected ‒ ADRB2 (rs1042713) and (rs1042714), ADRB3 (rs4994), GNB3 (rs5443), PPARA (rs4253778), PPARD (rs2016520), TCF7L2_IVS3 (rs7903146) and TCF7L2_IVS4 (rs12255372), PPARGC1A (rs8192678), MTHFR (rs1801131), PPARG (rs1801282), MTNR1B (rs10830963), SIRT1 (rs7069102).Results. In newborns with ELBW, we found a more frequent occurrence of the mutant allele A of the polymorphic locus rs8192678 in the PPARGC1A gene and the allele C of the polymorphic locus rs4253778 in the PPARA gene, in contrast to the adult population sample. But in newborns with ELBW, hyperglycemia is most likely associated with the carrier of the allele C rs1801282 of the PPARG gene (χ2 = 18.972, p < 0.001) and the allele T rs7903146 in the TCF7L2 gene (χ2 = 11.496, p < 0.001).Conclusions. The carriage of the allele С rs1801282 of the PPARG gene is characterized by the presence of a strong conjugation with hyperglycemia in newborns with extremely low body weight. It is desirable to monitor the level of glycemia in the conditions of neonatal intensive care units, taking into account the carriage of genes predisposing to hyperglycemia.

The problem of premature infants is well recognized in Russia and all over the world. The article discusses the mortality level and structure of extremely premature infant during 2015–2019. The aim of the study was to identify significant cause-effect relations for high mortality of premature infants and infants with extremely low body weight (ELBW) according to reports from obstetric departments, pediatric outpatient clinics, children's hospitals, statistical agencies, queries results from Territorial Compulsory Medical Insurance Fund (TCMIF) in Saint Petersburg and Russian Association of Human Reproduction (RAHR). The main demographic indices are presented by the Petrostat association. Russian Federal State Statistics Service (Rosstat) forms provided by the Center for Analysis and Prediction of Maternal and Child Health of the Saint Petersburg Health care Committee (No. 32 “Information on medical care for pregnant women, women in labour and new mothers” (approved by order of Rosstat No. 591 of 27.11.2015); No. 19 “Information on children with disabilities” registered in children's clinics (approved by order of Rosstat No. 866 of 27.12.2016); No. 14 “Information on the activities of medical facilities units providing inpatient medical care” (approved by order of Rosstat No. 723 of 05.12.2014); No. 30 “Information on the medical facility” (approved by order of Rosstat No. 483 of 03.08.2018 “On the approval of statistical tools for the organization of federal statistical observation in the field of healthcare by the Ministry of Health of the Russian Federation”) presented by Saint Petersburg Medical Informational and Analytical Center (MIAC)), and answers from TCMIF in Saint Petersburg and RARCH have been investigated. The authors have analyzed the fertility and mortality rates of premature infants, the group of children with ELBW has been established. High mortality levels have been revealed in the first weeks of life (22–23), they were mainly associated with infectious processes. The authors associate the premature delivery increase with the widespread implementation of assisted reproductive technology (ART). ART can be performed either via compulsory medical insurance funds, or other non-government sources. The assumption was proposed that there are possible violations of ART indications, contraindications, and the number of procedures. The ART efficacy is difficult to estimate as well due to insufficient information provided by Rosstat report form No. 32. The need of implementation of the new statistical form that will cover the data on the of ART administration, the possibility of efficacy estimation of modern invasive methods for infertility treatment and mandatory submission of reports about the use of these methods by medical facilities is discussed.

To evaluate the immunity indexes in the children who were born with bronchopulmonary dysplasia (BPD) of varying severity at very early delivery terms (22-27 weeks), dynamic examinations were performed in 35 infants: 17 children were with severe BPD; 18, with mild-severity and moderately severe BPD. The comparison group consisted of seven children born at 22-27 weeks of gestational age without signs of BPD. Relative numbers of lymphocyte subpopulations (CD3+, CD4+, CD8+, CD19+, CD16+CD56+, CD4+CD25+), and monocytes (CD14+CD64+, CD14+HLA-DR+) were determined by flow cytometry. The level of cytokines (IL-6, IL-8, IL-4) was measured by enzyme immunoassay technique. The features of immune status in children with BPD of severe, mild and moderate severity were discerned. It was found that the predictors of severe BPD development in the children born at very early terms, are: increased content of IL-8 at birth and at the age of 1 month, reduced level of expression on monocytes (CD64, HLA-DR) on the 1 month of life, and CD14+CD64+ cells at 38-40 weeks post conception. The revealed features of immune status in newborns with BPD can be used to assess the effectiveness of the therapy, which requires further research in this direction.

Background. The development of premature infants is slower than that of term ones, often due to nutritional status disorders in preterm infants. Objective. Our aim was to study the nutritional status, physical, and psychomotor development of infants.Methods. Nutritional status — the composition (the ratio of fat and fat-free tissues) and the value of lean body mass (LBM) — was assessed by plethysmography and densitometry; physical development — by measuring the mass and length of the body, the circumference of the head and chest, calculating the body mass index (BMI); psychomotor development — assessing compliance with the schedule of neuropsychological development of infants (GNOM). The examination was carried out at 12–14 and 16–18 weeks of the corrected age for preterm and actual age for full-term infants. Initially, the diet of infants was assessed by determining the amount, content of macronutrients and energy in the breast milk and/or milk formula and complementary food consumed. The diet was considered to be balanced if the diet parameters diverged not more than 10% of the norm.Results. The study included 23 preterm infants with extremely low (ELBW), 20 — with very low (VLBW), 34 — with low body weight (LBW), and 33 full-term infants. At 12–14 weeks of the corrected age, the magnitude of LBM in infants with ELBW — 3,397 (3,096; 3,608) and with VLBW — 3,824 (3,797; 3,899) was lower than in infants with LBW — 4,497 (4,034; 4,651) and full-term infants — 4,511 (3,887; 4,647) (Kruskal–Wallis test, p = 0.048). Protein balanced diet was in 2 (9%) infants with ELBW, energy balanced diet — in 1 (4%) infant. Among infants with ELBW, 17/23 (74%) referred to the risk group, 6/23 (26%) — to the developmental disorder group. Compared with infants with ELBW and VLBW, infants with LBW and full-term infants had a higher LBM and, correspondingly, higher body weight and BMI. Improvement of the nutritional status after 4–6 weeks due to correction of protein and energy consumption in infants with ELBW was accompanied by some increase in lean body mass, while its proportion was much higher and the proportion of fat mass was lower, which was accompanied by an improvement in the psychomotor development in individual infants: 5/23 (22%) became age-appropriate, and in the risk group of developmental disorders, the proportion of infants decreased from 17 (74%) to 13/23 (57%). The obtained results testify to the influence of nutritional status on the physical and psychomotor development of infants.Conclusion. The importance of dynamic assessment of the nutritional status of premature infants with individualized correction of their diet for improving the physical and psychomotor development of the child during the first year of life is shown.

To evaluate the immunity indexes in the children who were born with bronchopulmonary dysplasia (BPD) of varying severity at very early delivery terms (22-27 weeks), dynamic examinations were performed in 35 infants: 17 children were with severe BPD; 18, with mild-severity and moderately severe BPD. The comparison group consisted of seven children born at 22-27 weeks of gestational age without signs of BPD. Relative numbers of lymphocyte subpopulations (CD3+, CD4+ , CD8+ , CD19+ , CD16+CD56+, CD4+CD25+), and monocytes (CD14+CD64+ , CD14+ HLA-DR+) were determined by flow cytometry, The level of cytokines (IL-6, IL-8, IL-4) was measured by enzyme immunoassay technique. The features of immune status in children with BPD of severe, mild and moderate severity were discerned. It was found that the predictors of severe BPD development in the children born at very early terms, are: increased content of IL-8 at birth and at the age of 1 month, reduced level of expression on monocytes (CD64, HLA-DR) on the 1 month of life, and CD14+CD64+ cells at 38-40 weeks post conception. The revealed features of immune status in newborns with BPD can be used to assess the effectiveness of the therapy, which requires further research in this direction.

Background: Premature infants with extremely low and very low birth weight with a severe overlapping perinatal pathology often feature slower growth rate within the first year of life and require special nutritional support.Objective: Our aim was to study physical development of infants with protein-calorie deficiency in the setting of using a specialized protein- and calorie-rich pediatric milk product for enteral feeding.Methods: We analyzed tolerability and efficacy of clinical nutrition within the framework of a prospective two-month-long case series. We assessed actual children’s diets and the chemical composition thereof. We determined body weight and length, body mass index (BMI), adipodermal flap thickness over the triceps. Anabolic effect of clinical nutrition was assessed on the basis of transthyretin concentration dynamics.Results: The study involved 30 infants with protein-calorie deficiency (7 term infants and 23 premature infants) with a severe perinatal pathology. High tolerability of the formula under analysis was registered in most patients. Termination of functional gastrointestinal tract disorders (posseting, colics, flatulence, constipations) was observed in 23 (87%) patients. In most cases, the use of a protein- and calorie-rich formula as a part of a therapeutic diet helped to satisfy children’s protein demand and improve their weight/length parameters: BMI increased in 19 (72%) children, body weight — in 16 (63%), body length — in 24 (92%), adipodermal flap thickness over the triceps — in all the children (100%). We observed transthyretin concentration increase from 162 (157; 171) in the beginning of the study to 187 (170; 208) mg/l in the end thereof (p = 0.028).Conclusion: A specialized protein- and calorie-rich product for enteral feeding may be used for feeding infants with protein-calorie deficiency born with a severe a perinatal pathology, including premature infants.

The study estimated outcomes of 22–27 weeks of pregnancy according to the analysis of new statistic forms. The official statistic data on births and deaths of children with extremely low body weight in Russian Federation, federal Districts and Subjects in 2009 were used in this work. Mortality decreased in children 750–999 g and in a less degree in children 500–749 g. Dynamics of results showed the necessity of development and delivery to health care institutions of Russian Federation the new forms of statistic reports for monitoring, analysis and improvement of health care quality in delivery and management of extremely premature infants.