Background: Thanks to advancements in neonatal medicine, perinatal morbidity has been significantly reduced, but the number of high-risk neonates continues to rise. Efforts to predict neurodevelopmental outcomes at an early age remain limited. The aim of this study was to analyze perinatal predictors of neurodevelopmental outcomes in high-risk neonates. Methods: A prospective, longitudinal two-year study was conducted at the Pediatric Clinic of the University Clinical Center in Tuzla. The study included 151 neonates, with 99 in the test group (with known perinatal risk factors) and 52 in the control group (without risk factors). Early neurodevelopment was assessed using the Alberta Infant Motor Scale (AIMS). Standard statistical methods were applied for data processing. The study was approved by the Institutional Ethics Committee. Results: Of the 151 neonates observed, 108 (71.5%) had normal neurodevelopment at 18 months, 29 (19.2%) had mild disorders, and 14 (9.3%) had developmental delays. In the group with suboptimal neurodevelopment, significantly more twin pregnancies, health problems during pregnancy, unnatural births, artificial fertilization, and pregnancy complications were recorded. In neonates, there were significantly more premature births, hypoxic-ischemic encephalopathy, and intracranial hemorrhages. Significant correlations were found between the mother's age and parity and delayed neurodevelopment. Additionally, correlations were found between birth weight, gestational age, Apgar score, length of hospitalization, and NICU stay with neurodevelopmental delay. Gestational age and the Apgar score at 1 minute showed significant negative predictive value for neurodevelopmental delay. Conclusion: Prematurity and perinatal asphyxia remain the greatest risks for adverse neurodevelopmental outcomes in neonates. These factors should be the focus of continued medical research and clinical practice. Neonates at the highest risk of developmental delay and their families should be prioritized for early identification, long-term follow-up, and timely interventions.

Aim: To evaluate the incidence, characteristics, transmission, and outcomes of COVID-19 infection in hospitalized neonates in Tuzla Canton and to emphasize the importance of quality triage in the prevention and control of infection. Material and Methods: A retrospective cohort study, which included all consecutive neonates suspected of COVID-19 infection, and which required screening supervision in the triage department, from those who required hospital treatment at the Pediatric Clinic, University Clinical Center Tuzla for 12 months. (January 1 to December 31, 2020). Statistical analysis applied standard methods, and the research was approved by the Ethics Committee of the institution. Results: In the observed period, in the neonatal triage department, 111 neonates suspected to COVID-19 were treated, with no gender difference. Among them were 92 neonates of mothers suspected of COVID-19 (66 admitted immediately after birth, 26 readmitted after discharge home), and 19 neonates of mothers positive for COVID-19 (16 admitted immediately after birth, 3 readmitted). Cesarean delivery was a more common delivery option, and fever a more common symptom in COVID-19 positive mothers, but without statistical significance. The neonates from COVID-19 suspected mothers formed a heterogeneous group, with common perinatal problems, while neonates from COVID-19 positive mothers, hospitalized immediately after birth, were almost term neonates with appropriate birth weight, without need for a lot of treatment. All neonates hospitalized immediately after birth were negative for COVID-19.  The only three COVID-19 positive neonates were readmitted after previous discharge home, and they had mild symptoms, mostly one-day fever, and they all recovered completely. All of these neonates are under further follow-up after discharge from the hospital, and all are, for now, in good general condition, and all have continued to breastfeed. Conclusion: Neonates born to mothers with positive COVID-19 infection generally have favorable outcomes, with no convincing case of vertical transmission. Neonatal COVID-19 is mostly asymptomatic, acquired postnatally, and associated with favorable outcomes. The importance of quality triage in the prevention and control of infection is crucial, with consistent implementation of safe practices including proper patient isolation and appropriate protective equipment.

Aim Steady progress in intensive treatment worldwide has increased the survival of immature neonates, but with multiple invasive procedures, which have increased the risk of infection, thus the bacterial resistance to antibiotics. The aim of this study was to analyse the epidemiology of multidrug resistance pathogens as causative agents of neonatal sepsis in the neonatal intensive care unit. Methods A retrospective cohort study conducted at the Intensive care unit of the Paediatric Clinic of Tuzla over a three-year period (2016-2018) analysed epidemiology of neonatal sepsis caused by multidrug resistance pathogens. Statistical analysis applied standard methods, and the research was approved by the Ethics Committee of the institution. Results Of the total of 921 treated neonates, multidrug resistance (MDR) pathogens among causative agents of neonatal sepsis were found in 22 neonates (2.38%) with no gender difference. Prematurity and low birth weight were confirmed as the most significant risk factors. From the maternal risk factors a significant difference was found in the first birth and in vitro fertilization. Clinically, MDR sepsis manifested frequently as late onset sepsis, with longer hospital stay and higher mortality. The findings of leukopenia, thrombocytopenia and coagulation disorders were significant. Gram negative bacteria were frequently isolated, in particular Acinetobacter, which showed the greatest resistance to antibiotics. Conclusion Neonatal MDR sepsis is a threat to life, it complicates the treatment, increases costs and mortality. Outcomes can be improved by preventive strategies, earlier and more accurate diagnosis and rational use of antibiotics.

Introduction : Steady progress in intensive treatment worldwide has increased the survival of immature neonates, but with multiple invasive procedures, which has increased the risk of infection and, consequently, fungal sepsis. Candida is the dominant cause, with the rise of resistant non-albicans species. The mortality rate is high and requires timely suspicion and adequate treatment to counteract fatal outcomes. Objectives: To analyze the clinical and laboratory characteristics of Candida sepsis, compared to bacterial sepsis, in neonates treated in the neonatal intensive care unit. Methods: A retrospective cohort study conducted at the Intensive care unit of Pediatric Clinic Tuzla over a three-year period (2016-2018) analyzed the clinical and laboratory characteristics of neonates with Candida sepsis, evidenced by positive blood culture. The control group was neonates treated at the same time for proven bacterial sepsis. Statistical analysis applied standard methods, and the research was approved by the Ethics Committee of the institution. Results: Out of the total 921 neonates treated over a three-year period, culture-confirmed Candida sepsis was found in 48 (5.2%). Prematurity and low birth weight were the most significant risk factors and affected neonates had a more difficult clinical presentation, more receiving parenteral nutrition, mechanical ventilation, intravenous gamma globulin, and longer intensive treatment. Candida sepsis manifested mainly as late-onset. Laboratory abnormalities mainly included CRP elevation, anemia, leukocyte count deviations, and thrombocytopenia. There was no difference in mortality, 44 neonates recovered (91.7%), while 4 (8.3%) died. Antifungal therapy lasted 20.6 ± 6 days, and intensive treatment 38.2 ± 23.2 days, and was significantly longer compared to the control. All isolates were Candida species without in vitro resistance. In 8 neonates (16.7%) treatment complications were recorded. Conclusions: Neonatal Candida sepsis endangers life, complicates treatment, increases costs and mortality rate. Recovery depends on timely suspicion, adequate treatment, and supervision. Antifungal susceptibility is also important and requires monitoring of local epidemiological dynamics.

Introduction: Cytomegalovirus (CMV) infection is ubiquitous. It affects all age groups, and its clinical picture ranges from mild to severe, especially as a congenital infection in neonates. Aim: To determine frequency of CMV infection in pregnant women in Tuzla Canton (TC) and the risk factors that lead to the infection. Methods: This prospective study included 300 pregnant women from TC aged 18 to 42 years. CMV serology was performed on all participants, and in case of acute infection additionally IgG avidity test. Participants also completed the questionnaire on the risk factors for CMV infection. Results: The median age of the 300 women was 28 ±4.97 years. There were 161participants (53.6%) who classified their environment as urban and 295 (98.33%) were married. More than half of the women had completed secondary school 168 (56%). Positive IgG antibodies to CMV had 280 (93.0%) women. Positive IgM and IgG antibodies had 9 (3.0%) participants, but all of them had high IgG avidity, which indicates reinfection or recurrent CMV infection. There was a statistically significant higher number of seropositive participants living in rural areas than those living in urban areas (p= 0.048). Also, there was significantly higher percentage of positive anti-CMV IgG in pregnant women with lower education (p=0.04). Conclusion: In our region there is high seropositivity rates of IgG antibodies to CMV in pregnant women. No case of primary CMV infection was proven. The risk factors for CMV infection have been proven to be rural environment and lower level of education.

Aim: The aim of this study was to analyze risk factors and outcome of neonatal pneumothorax in Tuzla Canton. Methods: Neonates with chest X-ray confirmed pneumothorax in University Clinical Center of Tuzla, within a three-year period, from January 2015 to December 2017, were retrospectively studied. Participants were evaluated for baseline characteristics, predisposing factors of neonatal pneumothorax, accompanying disorders and mortality. Results: During the observed three-year period 11425 neonates were born in Tuzla Canton, with 7.33 % of preterm births, and 604 neonates were treated in NICU, with 265 neonates who required mechanical ventilation. Neonatal pneumothorax (NP) was diagnosed in 22 patients (9 term, 13 preterm), 12 (54.5%) were male. The incidence was 0.20% of total births, respectively 3.64% of those treated in NICU. The mean gestational age were 35.1 ± 3.0 weeks and birth weight 2 506.8 ± 727.7 grams. NP was mostly unilateral (72.7%) and right-sided. The most commonly associated diseases were: respiratory distress syndrome, intracranial haemorrhage, pneumonia, transient tachypnea and sepsis. In 8 (36.4%) neonates, the underlying cause of NP could be mechanical ventilation (secondary), whereas in 14 (63.6%) NP was spontaneous, without previous mechanical ventilation, although 11 of them required mechanical ventilation after pneumothorax. Conclusion: All perinatal risk factors were investigate, and significant differences in two observed groups related to mechanical ventilation were found for birth weight, gestational age, Caesarean section, length of mechanical ventilation, surfactant replacement therapy and outcome. Three (13.64%) neonates with NP died, and among risk factors with poor outcome, significant was only Apgar score in the first minute ≤ 5.

Prematurity is a risk factor for respiratory syncytial virus (RSV)-associated lower respiratory tract infections (LRTIs), due to immature humoral and cell-mediated immune system in preterm newborns, as well as their incomplete lung development. Palivizumab, a humanized monoclonal antibody against the F glycoprotein of RSV, is licensed for the prevention of severe RSV LRTI in children at high risk for the disease. This study is a part of a larger observational, retrospective-prospective epidemiological study (PONI) conducted at 72 sites across 23 countries in the northern temperate zone. The aim of our non-interventional study was to identify common predictors and factors associated with RSV LRTI hospitalization in non-prophylaxed, moderate-to-late preterm infants, born between 33 weeks and 0 days and 35 weeks and 6 days of gestation, and less than 6 months prior to or during the RSV season in Bosnia and Herzegovina (B&H). A total of 160 moderate-to-late preterm infants were included from four sites in B&H (Sarajevo, Tuzla, Mostar, and Banja Luka). We identified several significant intrinsic and extrinsic factors to be associated with the risk of RSV LRTI hospitalization in the preterm infants, including: comorbidities after birth, shorter hospital stay, admission to NICU/PICU while in the maternity ward, household smoking, low maternal age, breast feeding, number of family members, and history of family/paternal atopy. Overall, our results indicated that the risk of RSV LRTI in preterm newborns can be associated with different environmental and social/cultural factors, and further research is needed to comprehensively evaluate these associations.

Children with atopic dermatitis (AD) usually develop symptoms when they reach the age of 6-7 years, but the risk of developing respiratory allergies, asthma and allergic rhinitis (AR) remains high. In most children with AD, the development of asthma and AR is associated with sensitization to food allergens and/or aeroallergens, while only a small percentage missed atopic diathesis. In about 35% of children with AD, food allergy is the provoking cause, and 60% of infants who had AD in the first 3 months of life were sensitized against aeroallergens by the age of 5. The aim of the study was to follow development of asthma and AR and to assess the most significant risk factors for developing respiratory allergy. A total of 114 children with AD were followed up for five years. At annual visits, the severity of disease, total immunoglobulin E (IgE) antibody values, skin prick tests, specific IgE antibodies to food allergens and aeroallergens, and absolute eosinophil count were assessed. Information on the family history of atopy and AD, feeding patterns during infancy, data on sensitivity to food allergens and/or aeroallergens, and on the occurrence of bronchial obstruction and nose symptoms were obtained. Asthma developed in 36 children, median age 7.7 years; 33 children had symptoms of AR, and 13 children with AD had both diseases associated; 38 children had sensitivity to food, of which 24 developed asthma and 13 AR; asthma developed in 18/23 children with sensitivity to aeroallergens, and almost an equal number of children developed AR. The increased absolute eosinophil count and specific IgE to aeroallergens and food allergens were the best asthma predictors, while AR predictors were family history and early onset of AD. In conclusion, children with AD are at a significant risk of developing respiratory allergies, and those with the increased absolute eosinophil count, positive specific IgE to aeroallergens and food allergens, heredity of AD, and early onset of AD are at the highest risk. Identification of risk factors will enable us to improve the treatments of AD in order to reduce the severity of disease and prevent manifestation of respiratory allergy.

O1 Efficacy and safety of Canakinumab in patients with periodic fever syndromes (colchicine-resistant fmf, hids/mkd and traps): results from a phase 3, pivotal, umbrella trial F. De Benedetti, J. Anton, M. Gattorno, H. Lachmann, I. Kone-Paut, S. Ozen, J. Frenkel, A. Simon, A. Zeft, E. Ben-Chetrit, H.M. Hoffman, Y. Joubert, K. Lheritier, A. Speziale, J. Guido IRCCS Ospedale Pediatrico Bambino Gesú, Rome, Italy; Hospital Sant Joan de Déu, Barcelona, Spain; Pediatric Rheumatology, G. Gaslini Institute, Genoa, Italy; UK National Amyloidosis Centre, University College London Medical School, London, United Kingdom; Hôpital Kremlin Bicetre, University of Paris SUD, Paris, France; 6 Department of Pediatrics, Hacettepe University, Ankara, Turkey; University Medical Center Utrecht, Utrecht, Netherlands; Radboud University Medical Centre, Nijmegen, Netherlands; Pediatrics Rheumatology, Cleveland Clinic, Cleveland, USA; Rheumatology Unit, Hadassah—Hebrew University Medical Center, Jerusalem, Israel; University of California, San Diego, La Jolla, USA; Novartis Pharma AG, Basel, Switzerland Presenting author: F. De Benedetti Pediatric Rheumatology 2017, 15(Suppl 1):O1