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Lenticulostriate vasculopathy (LSV) is a relatively common fi nding in routine cranial ultrasound examination that has been associated with many infectious and non-infectious conditions. The aim of this review was to provide a better understanding of LSV ultrasound fi nding, as well as the need for further laboratory and imaging examinations in infants. The most of the published studies represented small series, with few prospective long-term studies involving the control groups. Authors have mostly found an association between LSV, especially higher-grade (although there is no universally accepted classifi cation) with congenital cytomegalovirus (CMV) infection, classifying those children as at risk for sensorineural hearing loss. In contrast, some authors pointed out that LSV could be found relatively often, and believe that isolated LSV, especially lower-grade, is not predictive for an unfavourable outcome and a long-term prognosis. Therefore, although 35 years have passed since the first publication of LSV, there is still no consensus among experts on the clinical signifi cance of isolated LSV, but caution is certainly needed given the fact that most infants with congenital CMV are asymptomatic.

S. Heljić, S. Terzić, S. Izetbegovíc, E. Vukas, H. Maksić, Nedim Strukar, A. Zovko, M. Martinovic et al.

Background: Cohort studies are useful in determining how risk factors and outcomes differ among regions, populations and available resources. The aim of this five-year cohort study of premature infants from Bosnia and Herzegovina was to examine the impact of mode of delivery and administration of prenatal corticosteroids on key neonatal outcomes. Methods: This cohort study included 734 infants with gestational age 24 32 weeks, admitted to the neonatal intensive care unit of the Pediatric Hospital in Sarajevo from 1 Jan 2012 to 31 Dec 2016, including both inborn infants and infants transported from the smaller hospitals throughout the country. We also examined the subgroup of 225 infants with gestational age 24 28 weeks for the same outcomes. Results: In the full cohort, cesarean delivery was associated with a lower incidence of severe intraventricular hemorrhage (IVH) [6.5% (cesarean section, CS) vs. 13% (vaginal delivery) OR 0.45, 95% CI: 0.26 0.78 (p < 0.01)], but not with increased survival to discharge. Administration of prenatal corticosteroids was associated with decreased mortality [13% (yes) vs 21% (no) OR 0.53, 95% CI: 0.33 0.84 (p < 0.01)]. In the subgroup of extremely premature infants, CS was associated with a higher incidence of respiratory distress syndrome and surfactant administration, and prenatal steroid administration was associated with a lower mortality rate. Multiple regression analysis showed birth weight to be a significant predictor of survival to discharge and both birth weight and delivery type to be significant predictors of severe IVH. In this model, antenatal steroid administration was not a significant predictor of survival or severe IVH. Conclusion: In this cohort of premature infants born in Bosnia and Herzegovina, survival was not influenced by delivery type. In the full cohort, CS was associated with decreased risk of severe IVH but this association was not seen in the subgroup of more premature infants. We found an association between prenatal corticosteroids and decreased mortality, but this did not remain significant with multiple regression analysis.

H. Maksić, S. Heljić, F. Skokić, Darinka Šumanović-Glamuzina, V. Milošević, A. Zlatanović, Notario Gerard

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.

S. Heljić, L. Hukeljić, S. Terzić, Raho Spahović

Objective: To assess predictive value of blood lactate measurements in infants during therapeutic hypothermia due to moderate to severe asphyxia in relation to early outcome. Patients and methods: We retrospectively evaluated records of 47 full-term newborns that underwent therapeutic hypothermia after moderate to severe perinatal asphyxia from January 2011 to December 2015. Criteria for whole body cooling were established according to Bristol Cooling Protocol UK, including clinical signs of HIE using Sarnat&Sarnat scale and aEEG. Blood samples were taken from venous catheter in recommended intervals (3, 6, 12, 24, 48, 72 hours). Early outcome is evaluated on the base of survival rate, neurologic status at discharge and presence of post hypoxic lesions confirmed with brain MRI. All investigated infants were categorized into 3 groups 1) Infants with normal brain MRI finding and normal neurologic examination at the discharge; 2) Infants with abnormal brain MRI finding at the discharge (with 2 subgroups depending of neurological status at the discharge); 3) Newborns with lethal outcome. Results: Mean value of blood lactate at admission for all subjects was 11.87 ± 5.41 (3.224.0), without statistical difference between groups. Three hours after beginning of cooling mean value was 8.36 ± 3.70 (2.2-17.0) with statistical difference between all groups of survived infants compared to infants who died. After 6 and 12 hours mean values were 6.311 ± 3.69 and 6.269 ± 3.37 respectively with statistical difference between neurologically asymptomatic infants (including those with MRI finding interpreted as a mild lesion) compared to infants with abnormal neurological examination at the discharge and infants who died. Values of blood lactate after 24h, 48h and 72 h were 4.46 ± 2.00 (1.0–11.7), 3.60 ± 1.36 (1.6–6.9), 3.36 ± 1.93 (1.29.3) respectively. After 24 h we did not find statistical difference between groups. Conclusion: Serial measurements of blood lactate during therapeutic hypothermia in asphyxiated infants are important. Initial value of lactate is not proved to be predictive, but prompt decreasing of lactate values within 24 hours of cooling is associated with better early outcome. *Correspondence to: Suada Heljić, MD, PhD, NICU, Pediatric Clinic, Clinical University Center Sarajevo, Bosnia and Herzegovina, Tel: +387 61 865 285 (M), +38733566439 (W); E-mail: heljicsuada@hotmail.com

S. Terzić, S. Heljić, N. Pojskić, E. Hasanbegović

Introduction: In spite of measures to avoid invasive mechanical ventilation, many preterm infants are still artificially ventilated. The need for intubation and positive pressure ventilation is associated with so-called ventilator-induced lung injury (VILI) and bronchopulmonary dysplasia (BPD). A lot of strategies are made in order to minimise VILI. One of these strategies is the use of permissive hypercapnia, in which clinicians use more gentle ventilatory strategies and accept higher than “normal” alveolar partial pressure of carbon dioxide (PaCO2) values. Although there are promising studies about the use of permissive hypercapnia in preterm infants, we are still not sure if and when this mode of treatment is safe.Aim: The aim of this study is to investigate conditions in which permissive hypercapnia is safe to prematurely born infants regarding their survival.Methods: The present study was conducted in a tertiary research and educational hospital, NICU, Pediatric Clinic, Clinical Center University of Sarajevo (Sarajevo, Bosnia and Herzegovina). All infants had chest X-ray at admission, and were treated for respiratory distress syndrome (RDS) with nasal continuous positive airway pressure (nCPAP), conventional mechanical ventilation (CMV), or high frequency oscillatory ventilation (HFOV). At admission we registered data regarding birth weight (BW), gestational age in weeks (GW), Apgar score and prenatally given steroids. Inclusion criteria were fulfilled by 200 infants. According to their mean PaCO2, patients were divided into hypercapnia and normocapnia groups. We analyzed the outcome (survival) of these two groups.Results: The two groups didn’t differ regarding GW, prenatally given steroids, RDS severity, surfactant use, 1- and 5-minute Apgar score, nor according to their CRIB score. Groups had also similar survival. After performing ROC analysis we have found that infants born ≤ 27 GW and ≤ 1,000 g treated with permissive hypercapnia, and infants with normocapnia born ≤ 26 GW and ≤ 980 g, have a prediction of negative outcome regarding survival, with a high level of accuracy.Conclusions: This study shows that ventilation with permissive hypercapnia of preterm infants with RDS is not safe, considering survival in children with GW ≤ 27 and BW ≤ 1,000 g.

S. Heljić, S. Užičanin, F. Catibusic, S. Zubčević

Objective: The aim of this study was to analyze prognostic indicators for mortality in neonates with seizures in a level III Neonatal Intensive Care Unit (NICU). Patients and methods: A cohort of 100 neonates with clinically manifested seizures hospitalized in the NICU during 4 years period was prospectively monitored for the first year of life. The cohort consisted of 33 preterm and 67 full-term babies with 60 male and 40 female infants. Results: The mortality rate in the first year of life of infants with seizures in the neonatal period was 23%. The most common cause of seizures was birth asphyxia for full-term infants and intra-periventricular hemorrhage for preterm infants. Death was more common in pre-term than term infants (p <0,005). Simple regression demonstrated statistically significant associations between death in the first year of life and a cluster of highly associated variables: resuscitation (p<0, 01), mechanical ventilation (p<0,01) and asphyxia (p<0,05). This cluster of variables significantly correlates with: gestational age (p<0, 05), birth weight (p<0, 05) and intracranial hemorrhage (p<0, 05). Conclusion: In this cohort of neonates with seizures asphyxia requiring neonatal resuscitation was the primary risk factor for death.

S. Heljić, H. Maksić, H. Begić, F. Skokić, Darinka Šumanović Glamuzina, T. Božić, S. Konjević, V. Milošević et al.

Background: Palivizumab is indicated for respiratory syncytial virus (RSV) prophylaxis in high-risk children. Methods: Observational study, based on 4 sites in Bosnia and Herzegovina (BH 365 (61.9%) infants in total were born before 33 weeks. Average gestational age of preterm infants enrolled for prematurity only was 30.2 ± 3.2 weeks; for preterm infants with BPD/CLD it was 28.3 ± 3.7 weeks. Overall average of palivizumab injections was 4.1 ± 1.0. Hospitalization rate related to severe lower respiratory infections (LRI) during the period of protection by palivizumab was 1.2%. Respiratory infections which deserved medical attention were observed in 3.7% infants included in palivizumab prophylaxis.Conclusion: RSV prophylaxis in B&H is provided systematically and successfully, following the national guidance established in 2009, with the aim of achieving a good cost-benefit ratio, with very low hospitalization rate for severe LRI in prophylaxed infants. New randomized controlled trials (RCTs) and American Academy of Pediatrics (AAP) guidance revised in 2014 will be taken into account in establishing a new national recommendation.

S. Terzić, S. Heljić, J. Panić, M. Sadikovic, H. Maksić

Introduction: Pneumothorax is a life threatening condition, more often seen in immature infants receiving mechanical ventilation. It carries a significant risk of death and impaired outcome. Objective: To determine predictive factors for the occurrence of pneumothorax in preterm infants with respiratory distress syndrome (RDS). Patients and methods: The present study was conducted in a tertiary research and educational hospital, NICU, Pediatric Clinic UKC Sarajevo, from January 2010 to December 2013. All infants had chest X-ray at admission, and were treated due to RDS with nasal continuous positive airway pressure (CPAP), mechanical ventilation, or high frequency oscillatory ventilation. At admission we registered data regarding birth weight, gestational age, Apgar score, prenatally given steroids. Inclusion criteria were fulfilled by 417 infants. Data about timing, circumstances, side and treatment of pneumothorax were gathered from medical records. Results: Mean birth weight was 1,477 g, mean gestational age 29.6 weeks. We report 98 infants who did not survive. We also report incidence of pneumothorax in 5% of the infants with RDS. In this study pneumothorax and non-pneumothorax groups didn’t differ regarding sex, gestational age (median 29 and 30) nor birth weight (p = 0.818). Apgar score at the 1 st and 5 th minute of life had no influence in genesis of pulmonary air leak, neither prenatally given steroids (p = 0.639), nor surfactant administration. There was a low coverage of preterm infants with prenatal steroids (overall 28.29%). We found that FiO 2 ≥ 0.4 in the first 12 hours of life, and need for mechanical ventilation are predicting factors for developing pneumothorax (p < 0.05). Conclusion: Together with mechanical ventilation, inspired fraction of oxygen higher than 40%, needed to provide adequate oxygenation in the first 12 hours of life in preterm infants, could be a predictive factor in selecting the highest risk babies for development of neonatal pneumothorax.

Z. Zvizdic, S. Heljić, Nusret Popović, J. Alajbegović-Halimić, E. Milisic, A. Jonuzi

Background: necrotizing enterocolitis is a serious condition that affects mostly preterm infants, with high mortality rate. Aim: to estimate the influence of potentially contributing factors of this multifactorial disease. Methods: the study group included 51 necrotizing enterocolitis infants who were less than 37 week gestation who were hospitalized in NICU during a five year period. The control group consisted of 71 patients with approximately the same gestational age and birth weight. Average gestational age in the study group was 30.2 weeks (SD 3.7), average birth weight 1502g (SD 781.5). Average postnatal age in the time of the presenting NEC was 18.2 days (SD 12.8). Results: Logistic regression estimates the influence of risk factors, which in our study related to the treatment of preterm infants on the likelihood of NEC development. Our regression model consisted of seven independent variables (nosocomial infections, mechanical ventilation, nasal continuous positive pressure, morphine, inotropes, blood transfusions, and H2 blockers), which were shown to have a statistically significant impact, X2 (7, n=1222) = 49.522, p<0.0001; two independent variables (nosocomial infection and H2 blockers use) were statistically significant. Preterm infants with nosocomial infection had a three times greater chance of developing NEC, and infants who received H2 blockers had a 1.5 higher risk. Conclusions: Underlying pathology of very low birth weight infants and their treatment in NICU contribute to NEC development. Identifying risk factors can be crucial for the early diagnosis and outcome of disease. Awareness of risk factors should influence changes in practice to reduce the risk of NEC.

Z. Zvizdic, S. Heljić, D. Zvizdic, I. Kalkan, S. Terzić, Raho Spahović, Amra Cengić

Objectives: Preterm newborns with patent ductus arteriosus (PDA) are at greater risk for bronchopulmonary dysplasia (BPD), decreased perfusion of vital organs and mortality. The aim of study was to determine relationship between the existence of PDA and the development of necrotizing enterocolitis (NEC) in preterm infants. Methods: The study included 51 preterm infants with necrotizing NEC, admitted to the neonatal intensive care unit (NICU) at the University Clinical Center Sarajevo. In patients with NEC, 30 patients were treated conservatively (NEC II group), while 21 patients were treated surgically (NEC III group). The control group consisted of 71 preterm infants without necrotizing enterocolitis. The PDA was diagnosed by the presence of bounding peripheral pulses, and confirmed by two-dimensional Doppler echocardiography. Results: A statistically significant difference in PDA frequency was observed between the NEC group of patients and control group (χ2=11.484; p=0.0007), between the NEC II and control group (χ2=11.033; p=0.0009) and between the NEC III group and control group (χ2=5.557; p=0.0184). Logistic regression analysis revealed that PDA is an independent risk factor for the development of NEC (OR=10.95; 95% CI: 2.10, 57.08). Conclusion: Our data suggest that PDA represents independent risk factor for the development of NEC in premature infants, probably due to the influence of PDA on compromising mesenteric perfusion. Keywords: patent ductus arteriosus, necrotizing enterocolitis, preterm infants

S. Zubčević, S. Heljić, F. Catibusic, S. Užičanin, M. Sadikovic, B. Krdzalic

Introduction: Neuroprotective benefit of therapeutic hypothermia in term newborns with hypoxic-ischemic encephalopathy (HIE) was assessed by analyzing survival and neurodevelopmental outcome of neonates subjected to this procedure. Material and methods: Newborns with gestational age > 36 weeks and < 6 hours of age with moderate to severe asphyxial encephalopathy underwent cooling protocol at a temperature of 33.5 °C for 72 hours and rewarming period of 6 hours. Outcome measures assessed were death and neurodevelopmental characteristics, which were compared at the different age using ASQ-3. Twenty-five children were assessed at age 3-6, 12-18 and 24-36 months. Median gestational age was 40 weeks, birth weight 3470 g, Apgar score 2/4 and pH on admission to the hospital 7.02. Four (16%) children died. Results: At the first assessment developmental categories of communication were normal in 78.9%, problem solving in 63.2%, personal-social in 68.4%, gross motor in 68.4%, and fine motor in 42.1% with a high need of retesting in this area. Second assessment was done in 17 patients: developmental categories of communication normal in 58.8%, problem solving in 70.6%, personal-social in 64.7%, gross motor in 64.7%, and fine motor in 35.3%. Third evaluation was done in 14 patients: developmental categories of communication were normal in 64.3%, problem solving in 71.4%, personal-social in 57.1%, gross motor in 64.3%, and fine motor in 42.9%. Conclusion: There was no correlation between baseline parameters and outcome. Results of the study are showing that therapeutic hypothermia in term newborns can provide better survival and less neurologic sequels in HIE patients.

S. Zubčević, S. Heljić, Raho Spahović, I. Kalkan, S. Terzić, M. Sadikovic

Studies are supporting neuroprotective benefi t of therapeutic hypothermia in term newborns with hypoxic-ischemic encephalopathy. We assessed survival and neurodevelopmental outcome of neonates subjected to the procedure and factors that may have infl uenced it. Newborns with gestational age of more than 36 weeks and less than 6 hours of age with moderate to severe asphyxi al encephalopathy underwent cooling protocol at a temperature of 33.5 °C for 72 hours and rewarming period of 6 hours. The outcome measures assessed were death and neurodevelopmental characteristics. Twenty-fi ve children were assessed during the period from October 2010 to October 2013. Median gestational age was 40 weeks, birth weight 3470 g, Apgar score 2/4 and pH on admission to the hospital 7.02. Four (16%) children died and two were lost for follow up. At the age of fi nal assessment, developmental cate gories of communication were normal in 68.4%, problem solving in 73.7%, personal-social in 68.4%, gross motor in 57.9%, and fimotor in 36.8% but with a high need of retesting in this area. Seven of 19 patients (36.8%) had completely normal results for all fi e categories, while three (15.8%) had abnormal results for all categories. None of the 18 parameters that were correlated with neurodevelopmental outcome showed statistical signifi cance. Amplitude integrated electroencephalography was done in ten patients and the most prominent fiwas discontinuous activity in eight patients. In conclusion, a relatively small number of patients and l imitations of this study design precluded any far-reaching conclusions, but we think that this method can provide better survival and less neurologic sequels in hypoxic-ischemic encephalopathy patients.

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