The relationship between neonatal stress in preterm infants and developmental outcomes at the corrected age of 24-30 months.

Aim: The aim of research was to study the relationship between the stress experienced by preterm infants in the neonatal intensive care unit (NICU) and developmental status in the follow up, and to establish factors, associated with their neurodevelopment. Methods: The first stage of research involved measuring stress markers (cortisol, melatonin) in infants (n = 56) during their NICU stay; the second phase assessed the developmental status at the corrected age of 24-30 months. Results: The total ASQ-3 score, communication, problem solving, and personal-social skills scores at the corrected age of 24-30 months were positively correlated with melatonin level determined in the neonatal period (r = 0.31, p = 0.026; r = 0.36, p = 0.009; r = 0.30, p = 0.033, and r = 0.32; p = 0.022 respectively). In the same time, ASQ-3 communication and personal-social scores were negatively correlated with cortisol level (r = -0.31, p = 0.043; r = -0.35, p = 0.022). The ROC-curve analysis revealed that a decrease of melatonin below 3.44 ng/mL and 3.71 ng/mL during the neonatal period could predict communication and problem-solving delay, respectively. An increase in cortisol above 0.64 mcg/dl is predictive in personal-social delay. Negative correlation was identified between the NICU and total hospital stay duration and ASQ-3 communication scores in the follow-up (r = -0.27; p = 0.049 and r = -0.41; p = 0.002, respectively). The duration of mechanical ventilation was negatively correlated with gross motor scores (r = -0.46; p = 0.043). Apgar score was positively correlated with ASQ-3 communication (r = 0.29; p = 0.032) and personal-social scores (r = 0.28; p = 0.034); maternal age-with ASQ-3 total (r = 0.29; p = 0.034), communication (r = 0.37; p = 0.006), and personal-social scores (r = 0.29; p = 0.041). Positive correlations were observed between gestational age and communication scores (r = 0.28; p = 0.033). Infants who suffered neonatal sepsis had significantly often delay of communication (p = 0.014) and gross motor skills (p = 0.016). Children who required mechanical ventilation were more likely to have communication delay (p = 0.034). Conclusion: Developmental outcomes in preterm infants at the corrected age of 24-30 months were associated with neonatal stress. Correlations between the communication, problem-solving and personal-social development in the follow up and cortisol and melatonin levels determined in the neonatal period supported this evidence. Factors as low gestational age, duration of hospital and NICU stay, mechanical ventilation, and sepsis were associated with more frequent delays in communication, gross motor and problems-solving skills.

The Relationship between COVID-19 Severity in Children and Immunoregulatory Gene Polymorphism.

Coronavirus disease (COVID-19) and its outcomes remain one of the most challenging problems today. COVID-19 in children could be asymptomatic, but can result in a fatal outcome; therefore, predictions of the disease severity are important. The goal was to investigate the human genetic factors that could be associated with COVID-19 severity in children. Single-nucleotide polymorphisms of the following genes were studied: ACE2 (rs2074192), IFNAR2 (rs2236757), TYK2 (rs2304256), OAS1 (rs10774671), OAS3 (rs10735079), CD40 (rs4813003), FCGR2A (rs1801274) and CASP3 (rs113420705). In the case-control study were 30 children with mild or moderate course of the disease; 30 with severe COVID-19 symptoms and multisystem inflammatory syndrome in children (MIS-C) and 15 who were healthy, and who did not have SARS-CoV-2 (PCR negative, Ig G negative). The study revealed that ACE2 rs2074192 (allele T), IFNAR2 rs2236757 (allele A), OAS1 rs10774671 (allele A), CD40 rs4813003 (allele C), CASP3 rs113420705 (allele C) and male sex contribute to severe COVID-19 course and MIS-C in 85.6% of cases. The World Health Organization reported that new SARS-CoV-2 variants may cause previously unseen symptoms in children. Although the study has limitations due to cohort size, the findings can help provide a better understanding of SARS-CoV-2 infection and proactive pediatric patient management.

Triglyceride glucose index, pediatric NAFLD fibrosis index, and triglyceride-to-high-density lipoprotein cholesterol ratio are the most predictive markers of the metabolically unhealthy phenotype in overweight/obese adolescent boys.

Introduction: The prevalence of obesity constantly increases worldwide and definitely increases the risk of premature death in early adulthood. While there is no treatment yet with proven efficacy for the metabolic clamp such as arterial hypertension, dyslipidemia, insulin resistance, diabetes type 2, and fatty liver disease, it is imperative to find a way to decrease cardiometabolic complications. Early prevention strategies beginning in childhood are the most logical step to reduce future cardiovascular morbidity and mortality. Therefore, the aim of the current study is to determine the most sensitive and specific predictive markers of the metabolically unhealthy phenotype with high cardiometabolic risk in overweight/obese adolescent boys. Methods: This study was carried out at the Ternopil Regional Children's hospital (Western Ukraine) and involved 254 randomly chosen adolescent overweight or obese boys [median age was 16.0 (15.0,16.1) years]. A control group of 30 healthy children with proportional body weight comparable in gender and age to the main group was presented. A list of anthropometrical markers with biochemical values of carbohydrate and lipid metabolism with hepatic enzymes was determined. All overweight/obese boys were divided into three groups: 51.2% of the boys with metabolic syndrome (MetS) based on the IDF criteria; 19.7% of the boys were metabolically healthy obese (MHO) without hypertension, dyslipidemia, and hyperglycemia; and the rest of the boys (29.1%) were classified as metabolically unhealthy obese (MUO) with only one criterion (hypertension, dyslipidemia, or hyperglycemia). Results: Based on multiple logistic regression analysis that included all anthropometric and biochemical values and calculated indexes in boys from the MHO group and MetS, it was revealed that the maximum likelihood in the prediction of MetS makes the combination of triglyceride glucose index, pediatric nonalcoholic fatty liver disease fibrosis index (PNFI), and triglyceride-to-high-density lipoprotein cholesterol ratio (R2 =0.713, p<0.000). By tracing the receiver operating characteristic curve, the model is confirmed as a good predictor of MetS (AUC=0.898, odds ratio=27.111 percentage correct=86.03%) in overweight and obese boys. Conclusion: Triglyceride glucose index, pediatric NAFLD fibrosis index, and triglyceride-to-high-density lipoprotein cholesterol ratio are a valuable combination of predictive markers of the metabolically unhealthy phenotype in Ukrainian overweight/obese boys.

Skin-to-skin contact-An effective intervention on pain and stress reduction in preterm infants.

Introduction: The outcomes of pain and stress in preterm infants in the neonatal intensive care units (NICUs) compel the continued search for pain- and stress-reducing interventions. The objective of the study: To investigate how skin-to-skin contact (SSC) influences chronic pain and stress in preterm infants in the NICU. Materials and methods: The study included 140 preterm infants in the NICU with gestational age less than 34 weeks. The overall design was a baseline-response design. Urine and saliva were collected before (baseline) and after SSC to measure pain and stress markers by enzyme immunoassay method. The behavioral indicators of chronic pain were assessed using the EDIN (Échelle Douleur Inconfort Nouveau-Né-neonatal pain and discomfort). Results: There was a significant decrease in the dopamine level in preterm infants after SSC in comparison with baseline values (85.99 [69.35; 112.20] pg/ml vs. 132.20 [104.80; 183.70] pg/ml), p < 0.001. The ß-endorphin and serotonin levels increased after SSC (40.09 [26.81; 70.63] pg/ml vs. 29.87 [20.61; 46.94] pg/ml, p = 0.009 and 25.49 [20.45; 40.08] ng/ml vs. 22.30 [15.13; 31.65] ng/ml, p = 0.011, respectively). A significant decrease in cortisol levels in saliva and urine after SSC in comparison with baseline values (0.125 [0.079; 0.225] µg/dl vs. 0.371 [0.188; 1.002] µg/dl, p = 0.000 and 27.06 [14.59; 35.35] ng/ml vs. 35.25 [19.78; 61.94] ng/ml, p = 0.001, with a simultaneous increase of oxytocin level (57.00 [36.55; 88.49] pg/ml vs. 38.20 [28.78; 56.04] pg/ml, p = 0.009 were revealed. The total pain EDIN score in infants after SSC was below 6 points, significantly decreasing compared to the baseline (p < 0.05). Conclusion: Preterm infants in the NICU experience stress and pain, which were confirmed by the EDIN pain scale and laboratory markers. The level of dopamine and cortisol as pain and stress hormones were reliably high, and normalized after regular SSC. Simultaneously, pain-relieving and anti-stress markers of oxytocin, ß-endorphin and serotonin reliably increased in preterm infants in response to the SSC.

Peculiarities of melatonin levels in preterm infants.

BACKGROUND: Melatonin plays an important role in organism functioning, child growth, and development. Of particular importance is melatonin for preterm infants. The aim of our research was to study the peculiarities of melatonin levels depending on various factors in preterm infants with gestational age (GA) of less than 34 weeks. METHODS: The study involved 104 preterm infants with GA less than 34 weeks who were treated in the neonatal intensive care unit (NICU). The level of melatonin in urine samples was determined by an enzyme-linked immunosorbent assay. RESULTS: Melatonin concentration was significantly lower in extremely and very preterm infants compared to moderate preterm (3.57 [2.10; 5.06] ng/ml vs. 4.96 [3.20; 8.42] ng/ml, p = 0.007) and was positively correlated with GA (Spearman r = 0.32; p < 0.001). Positive correlations were revealed between melatonin levels and Apgar scores at the 1st (Spearman r = 0.31; p = 0.001) and 5th minutes after birth (Spearman r = 0.35; p < 0.001). Melatonin levels were lower in newborns with respiratory distress syndrome (p = 0.011). No significant correlations were found between melatonin concentration and birth weight (Spearman r = 0.15; p = 0.130). There were no associations of melatonin concentrations and mode of delivery (p = 0.914), the incidence of early-onset sepsis (p = 0.370) and intraventricular hemorrhages (p = 0.501), and mechanical ventilation (p = 0.090). The results of multiple regression showed that gestational age at birth was the most significant predictor of melatonin level in preterm infants (B = 0.507; p = 0.001). CONCLUSION: Gestational age and the Apgar score were associated with decreased melatonin levels in preterm infants. The level of melatonin in extremely and very preterm infants was lower compared to moderate preterm infants.

Skin-to-skin contact to support preterm infants and reduce NICU-related stress.

OBJECTIVE: Hospitalization in the neonatal intensive care unit (NICU) with numerous painful medical interventions, being separated from parents, leads to the high risk of chronic stress for preterm infants. Today, many NICUs use more appropriate developmental care and pain management, but the early and long-term outcomes of stress in these vulnerable infants require searching for more stress-reducing interventions in neonatal care. The objective of the study was to investigate how skin-to-skin contact (SSC) can influence the biologic stress levels in preterm infants in the NICU by assessing cortisol and oxytocin levels. PARTICIPANTS AND METHODS: The study included 71 preterm infants with gestational age less than 34 + 0/7 weeks who were recruited from level III NICU. The overall design was a baseline-response design. Saliva and urine were collected before (baseline) and after skin-to-skin contact to measure salivary cortisol and urinary oxytocin by enzyme immunoassay method. RESULTS: The infants' baseline hormonal status was represented by the following indicators: the level of salivary cortisol was 0.402 [0.227; 1,271] µg/dl, urinary oxytocin 48.88 [32.97; 88.11] pg/ml. There was a decrease in salivary cortisol levels to 0.157 [0.088; 0.351] µg/dl compared to baseline (p Ë‚ 0.001) with a simultaneous increase of the urinary oxytocin level -73.59 [45.18; 108.8] pg/ml (p = 0.028) in response to SSC. CONCLUSION: Preterm infants in the NICU experience significant stress, characterized by hormonal imbalance: an increased level of the stress hormone cortisol and a decreased level of the anti-stress hormone oxytocin. Skin-to-skin contact helps to ameliorate the hormonal stress in preterm infants by activating the oxytocin release with simultaneous reduction of cortisol secretion.

Assessment and Correction of Stress in Preterm Infants and Their Mothers.

OBJECTIVE: To investigate how skin-to-skin contact influences the stress levels in preterm infants in the neonatal intensive care unit and their mothers. MATERIALS AND METHODS: The study included 60 preterm infants with gestational age less than 32 weeks, who were treated in the neonatal intensive care unit, and their mothers. The overall design was a baseline-response design. Saliva was collected before (baseline) and after skinto-skin contact to measure free cortisol by enzyme immunoassay method. RESULTS: Infant baseline salivary cortisol level was 0.587 [0.239; 1.714] µg/dL. It was significantly higher in neonates who had invasive ventilation (1.00 [0.38; 2.44]) µg/dL compared to non-ventilated infants (0.335 [0.156; 1.236]) µg/dL, P = .022 and was positively correlated with the duration of ventilation (r = 0.70; P = .0000). Maternal baseline salivary cortisol level was 0.212 [0.123; 0.378] µg/dL. There was significant decreasing of salivary cortisol after Kangaroo mother care with skin-to-skin contact in infants (0.162 [0.111; 0.231]) µg/dL, P < .001 and mothers (0.096 [0.077; 0.156]) µg/dL, P < .001. CONCLUSION: Preterm infants in the neonatal intensive care unit and their mothers experience stress which can be confirmed by the increased baseline cortisol levels. Kangaroo mother care with skin-to-skin contact reduces the stress and normalizes salivary cortisol levels in both the infant in the neonatal intensive care unit and the mother.

Prevalence of arterial hypertension among Ukrainian students: the comparison of European and American guidelines.

INTRODUCTION: Arterial hypertension (HTN) among children is progressively increasing. These concerns have led to an update of the guidelines about childhood hypertension by the European Society of Hypertension (ESH) in 2016 and the American Academy of Pediatrics (AAP) in 2017, and their thresholds for HTN differ. The current research aims to compare the prevalence of hypertension in Ukrainian teenagers using 2 different guidelines and to check the impact of gender, age, and excess weight on hypertension. MATERIAL AND METHODS: The sample includes 540 Ukrainian students of 2 secondary urban schools, aged 10-17 years. Blood pressure and anthropometrical measurements were taken and compared with percentile tables. RESULTS: The prevalence of abnormal BP (11.3% and 15.2%) and HTN (1.9% and 4.1%) was determined with ESH and AAP guidelines, respectively, and they strongly depended on which definitions and criteria were used. Boys were much more predisposed to abnormal BP. Comparing both guidelines, there was no significant difference in HTN prevalence in children aged 10-12 years; nevertheless, AAP recognized HTN almost twice as often in teenagers aged ≥ 13 years. Excess body weight was identified in 17.2% of the school-age children, twice as frequently as in males. CONCLUSIONS: The results have shown a higher prevalence of HTN in teenagers and children with excessive weight more significant in boys and between children with positive markers of abdominal obesity due to both guidelines, without a significant difference in prevalence after re-classification; however, AAP recommendations might be preferable.

Influence of dietary and activity patterns on weight status of Ukrainian school aged children.

OBJECTIVES: Dietary patterns and physical activity have significant influence on weight status. Despite numerous studies related to this topic, there is no existing research which provides complete population-based studies that identify the most significant predictors of pediatric obesity. Therefore, it has become the major goal of our study. SUBJECTS AND METHODS: Three hundred school students between 10 and 17 years of age were participating in our study. All of them are currently attending various schools in city of Ternopil, Ukraine. Anthropometric measurements were performed for all participants. Information about food consumption and physical activity was obtained from distributed questionnaire. Logistic regression was used to identify the significant predictors of obesity. RESULTS: Lack of physical activity during week (OR=2.59 [95% CI 1.10-6.08]), long screen time in weekdays (OR=2.94 [95% CI 1.13-7.69]) and weekends (OR=3.63 [95% CI 1.55-8.50]), frequent consumption (OR=2.60 [95% CI 1.30-5.19]) and high amounts (OR=2.52 [95% CI 1.26-5.05]) of sweet beverages, fast-food consumption (OR=30.97 [95% CI 1.46-657.60]) and overeating (OR=3.99 [95% CI 1.26-5.05]) have increased chance to be overweight in children 10-17 years of age (p<0.05). CONCLUSION: Decreased frequency in moderate physical activity per week, increased amount of sugar-sweetened beverages, fast-food consumption per day and food consumption without hunger, appear to be the most significant predictors of overweight and obesity among Ukrainian school-aged children.

The association between vitamin D deficiency and metabolic syndrome in Ukrainian adolescents with overweight and obesity.

PURPOSE: This work aims to determine the association between vitamin D deficiency and metabolic syndrome in overweight and obese adolescents from Ukraine. METHODS: Anthropometric measurements were taken and general and biochemical examinations were performed on 136 obese and overweight adolescents and 60 adolescents with normal body weight. The vitamin D status was determined using 25-hydroxyvitamin D (25(OH)D) (calcidiol) levels in blood serum. To establish the factors influencing vitamin D status, the subjects were asked to answer a questionnaire and 2007 International Diabetes Federation diagnostic criteria were used to determine the incidence of metabolic syndrome. All research results were processed statistically. RESULTS: A calcidiol sufficiency level was found in 3.9% of obese adolescents and 6.7% of overweight adolescents. Metabolic syndrome was found in 64.4% of obese adolescents with vitamin D deficiency, and in 26.2% of overweight adolescents. Factors associated with an increased risk of developing vitamin D deficiency in adolescents with metabolic syndrome included male sex (p=0.042), low income per family member (p=0.040), daily milk consumption of up to 1 cup per day (p=0.001), physical activity (p=0.001), duration of outdoor stays (p=0.001), and passive rest in front of a computer or television (p=0.001). Adolescents with metabolic syndrome were found predominance of body mass index (p<0.001), waist circumference (p<0.001), fasting blood glucose level (Р<0.001), and decreased calcidiol level (p=0.022). Among metabolic syndrome components, vitamin D deficiency was strongly associated with waist circumference and increased fasting blood glucose (p<0.05). CONCLUSION: Vitamin D deficiency is prevalent in overweight and obese adolescents from Ukraine. Vitamin D deficiency is associated with metabolic syndrome criteria in overweight and obese adolescents.

Multisystem inflammatory syndrome in children (MIS-C) temporally associated with SARS-CoV-2: the first clinical case in Ternopil, Ukraine.

INTRODUCTION: Coronavirus disease (COVID-19) has led to a global pandemic among patients of all ages around the world. A new delayed inflammatory syndrome, with potentially severe evolution, has been described in the pediatric population, a population previously considered to be less vulnerable to the severe forms of COVID-19. CASE REPORT: We describe the first clinical case of multisystem inflammatory syndrome (MIS-C) in a 7-year-old child of the Ternopil region, Ukraine. Our clinical case fulfills the Royal College of Paediatrics and Child Health definition of MIS-C temporarily associated with COVID-19 -systemic disease with long-term fever, multiorgan dysfunction, laboratory evidence of hyperinflammation, positive SARS-CoV-2 tests, and the absence of an alternative cause that would explain the clinical picture. The patient was treated according to the treatment guidelines and subsequently was discharged with the resolution of his clinical symptoms. CONCLUSIONS: This clinical case draws the attention of general practitioners and pediatricians to the importance of timely diagnosis of a rare, but potentially severe multisystem inflammatory syndrome temporarily associated with COVID-19 in children.

Severe scarlet fever in a child with Down syndrome - a case report.

INTRODUCTION: Scarlet fever is an acute infectious disease that is characterized by development of characteristic pin-point exanthema in a patient with signs of streptococcal pharyngitis and tonsillitis. Nowadays, due to effective antibacterial treatment, severe complicated cases of scarlet fever are occasionally rare. Because of immunity particularities, patients with Down syndrome are predisposed to bacterial respiratory diseases (and scarlet fever among them), that usually have prolonged complicated course. CASE REPORT: A clinical case of scarlet fever in a patient with Down syndrome was analyzed. The disease had a severe course with a specific skin syndrome and was complicated by pneumonia. Hospitalization and adequate treatment of the patient led to his complete recovery despite late initiation of antibacterial medicine. DISCUSSION: A long severe complicated course of the disease in the presented case was caused by combination of the late initiation of antibacterial treatment and the patient's personal particularities of reactivity. CONCLUSIONS: Patients with Down syndrome should be adequately monitored by family doctors in case of pharyngitis with early testing for group A hemolytic Streptococcus infection and administration of the correct antibacterial treatment, if the test is positive.

Relation of carbohydrate exchange markers with vitamin D status in adolescents with overweight and obesity.

INTRODUCTION: In the case of obesity and excessive body weight, the deficiency of vitamin D increases, which significantly impairs metabolic processes in the body, especially fatty and carbohydrate metabolism. Vitamin D metabolites affect insulin sensitivity of cells. THE AIM OF THE STUDY: was to determine the relationship between vitamin D and carbohydrate metabolism in adolescents with excessive body weight and obesi-ty. MATERIAL AND METHODS: 139 adolescents were examined. The mean age of children was 15.5 ±2.3 years. 65 adolescents with excessive weight and 74 obesity teenagers were examined. Parameters that were determined in all children included: undertaking anthropometric measurements, general examinations, biochemical parameters, including carbohydrate metabolism: fasting glucose, insulin, oral glucose tolerant test, measuring the homeostasis model assessment for insulin resistance, blood pressure measurement and determination of vitamin D status. RESULTS: The features of changes carbohydrate metabolism markers in adolescents with overweight and obesity, depending on the level of serum 25(OH)D, have been established. Correlations between vitamin D status and markers of carbohydrate metabolism such as basal insulin level (p = 0.000) and HOMA-IR index (p = 0.000) and anthropometric indices: body mass index (p = 0.000), waist circumference (p = 0.000) and hip circumference (p = 0.001), waist-hip ratio (p = 0.000), waist-to-height ratio (p = 0.000) have been determined. CONCLUSIONS: The study has established prognostically significant biochemical (basal insulin), and anthropometric (body mass index, waist circumfer-ence, waist-hip ratio, and waist-to-height ratio) markers resulting in vitamin D deficiency development in children with excessive body weight and obesity.

Epidemiological aspects of obesity and systemic hypertension amongschool children of Western Ukraine.

INTRODUCTION: Systemic hypertension (SH) is a major long-term health condition and is the leading cause of premature death among adults throughout the world, including developed, developing, and lesser developed countries.In recent years there has been a progressive increase in SH among children and adolescents. Epidemiological studies demonstrated an overall increase in the prevalence of hypertension. SH is rarely recorded isolated and is often combined with obesity or the metabolic syndrome. AIM OF THE STUDY: The aim of our research was to study the prevalence of overweight, obesity, and systemic hypertension in Ukrainian school children aged 10-16 years. MATERIAL AND METHODS: 540 pupils of two secondary schools in the city of Ternopil, aged 10-16 years, were involved. Blood pressure was measured under standard conditions using the standard technique. To assess the physical development of each child, indicators of body weight, height, waist circumferences and body mass index were compared with percentile tables. RESULTS: The study has demonstrated that the prevalence of overweight is 11.1% and obesity 4.8% among pupils of Ternopil. The elevated blood pressure was found in 50 % of overweight or obese pupils. SH was found in 13.3% of children (11.8% of girls and 15.1% of boys), where pre-hypertension (p<0,01) and SH 1st (p<0,01) stages were observed twice as often in boys than in girls, and normal BP was recorded less frequently (p<0,01). CONCLUSIONS: The boys are three times more often obese than girls and 1.4 times more often overweight. The blood pressure is directly correlated with increased BMI, waist and hip circumference in the examined children. The abdominal obesity is a predictor of hypertension in adolescents. The result of the present study has demonstrated the real epidemiology of obesity and systemic hypertension in children and adolescents, and should motivate family doctors and paediatricians to prevent this pathology in Ukraine.

[Permanent neonatal diabetes mellitus in a young Ukrainian child]. / Przetrwala cukrzyca noworodkowa u dziecka z Ukrainy.

Diabetes mellitus is a chronic metabolic disease with the manifestation possible in any period of life. The incidence of diabetes is rising around the world, and studies show that children are at an increasing risk of developing the disease. Type 1 diabetes accounts for over 90% of childhood and adolescent diabetes, although less than 10% of children suffer from type 2 diabetes. Over the last few decades, inherited monogenic forms of DM were discovered and studied. An extremely rare form of diabetes (less than 1-2% of all diabetes in young people), with neonatal diabetes as a subset, and is usually suspected if a child is diagnosed with diabetes at less than 6 months of age. We present the first case reported in Ukraine of a child diagnosed with permanent neonatal diabetes resulting from a EIF2AK3 gene missense mutation of exon 15 (WolcottRallison Syndrome). Despite low incidence of the permanent neonatal diabetes, this diagnosis should be considered in infants with persistent hyperglycaemia requiring insulin therapy.