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Öğe All-Trans-Retinoic Acid Attenuates Intestinal Injury in a Neonatal Rat Model of Necrotizing Enterocolitis(Karger, 2013) Ozdemir, Ramazan; Yurttutan, Sadik; Sari, Fatma Nur; Oncel, Mehmet Yekta; Erdeve, Omer; Unverdi, Hatice Germen; Uysal, BulentBackground: Ischemia/reperfusion-induced intestinal injury is mediated by reactive oxygen species and inflammatory mediators. Objectives: This study was designed to evaluate whether all-trans-retinoic acid (ATRA) administration can attenuate intestinal injury and to analyze the antioxidant and anti-inflammatory effects of ATRA in a neonatal rat model of necrotizing enterocolitis (NEC). Methods: Twenty-nine Wistar albino rat pups were randomly divided into 3 groups: group 1 = control, group 2 = NEC and saline, and group 3 = NEC and ATRA treatment. NEC was induced by hyperosmolar enteral formula feeding and exposure to hypoxia after cold stress at +4 degrees C and oxygen. Pups in group 3 were injected intraperitoneally with ATRA (0.5 mg/kg body weight) once a day prior to each NEC procedure, beginning on postnatal day 1 and daily through postnatal day 4. The pups were killed on the 4th day and their intestinal tissues were harvested for biochemical and histopathological analysis. Results: Mucosal injury scores and intestinal malondialdehyde levels in group 2 were found to be significantly higher than other groups (p < 0.05). Intestinal superoxide dismutase and glutathione peroxidase activities in group 3 were significantly higher than group 2 (p = 0.04 and p = 0.04, respectively). Intestinal tissue tumor necrosis factor-alpha levels were significantly reduced with ATRA treatment in group 3 compared to group 2 (p < 0.001). Conclusions: It is likely that oxidative stress and inflammatory mediators contributed to the pathogenesis of NEC and that ATRA had a protective effect on intestinal injury through its anti-inflammatory and antioxidant properties. Copyright (c) 2013 S. Karger AG, BaselÖğe Beneficial effects of Etanercept on experimental necrotizing enterocolitis(Springer, 2014) Yurttutan, Sadik; Ozdemir, Ramazan; Canpolat, Fuat Emre; Oncel, Mehmet Yekta; Unverdi, Hatice Germen; Uysal, Bulent; Erdeve, OmerTissue damage in necrotizing enterocolitis (NEC) of infants occurs as a result of an uncontrolled inflammatory response. The aim of this study was to investigate any potential anti-inflammatory effects that Etanercept may have on the inflammatory response in an experimental NEC model in newborn rats. Newborn pups were randomized into three groups immediately after birth (Control, NEC + Placebo and NEC + Etanercept). Pups in the NEC + Placebo and NEC + Etanercept groups were subjected to an NEC-inducing protocol (hypercarbia, hypothermia and hyperoxia) twice a day for 3 days. Pups in the NEC + Etanercept group were given an intraperitoneal injection of Etanercept. Rats were harvested for biochemical and histopathological examinations. The histopathological injury score of rats in the NEC + Placebo group was significantly higher compared to the NEC + Etanercept and Control groups (p < 0.05 for both comparisons). Tissue levels of tumor necrosis factor-alpha, interleukin-1 beta, and malondialdehyde were higher in the placebo group compared to the Etanercept group. Our results suggest that Etanercept attenuates intestinal tissue damage in NEC by reducing inflammation and blocking the production of free-oxygen radicals, while also reducing tissue levels of tumor necrosis factor-alpha and interleukin-1 beta.Öğe Colchicine Protects against Hyperoxic Lung Injury in Neonatal Rats(Karger, 2012) Ozdemir, Ramazan; Yurttutan, Sadik; Talim, Beril; Uysal, Bulent; Erdeve, Omer; Oguz, Serife Suna; Dilmen, UgurBackground: Bronchopulmonary dysplasia (BPD) is characterized by inflammation, fibrosis and mucosal necrosis, which leads to emphysematous coalescence of alveoli. Objective: We tested whether prophylaxis with colchicine, an anti-inflammatory, antioxidant and antifibrotic drug, would decrease the severity of lung injury in an animal model of BPD. Methods: Twenty-five rat pups were divided into three groups: control (n = 8), hyperoxia (n = 7), and hyperoxia + colchicine (n = 10). The hyperoxia groups were exposed to >95% oxygen from day 1 to 10 of life. On day 10, the animals were sacrificed and the lungs were processed for histology and biochemical analysis. Lung morphology was assessed by the mean linear intercept (MLI), a measure of alveolar size. The degree of lung inflammation and antioxidant capacity were assessed by quantifying lung homogenate tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), malondialde-hyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. Results: Colchicine significantly decreased lung damage as determined by the MLI in the c groups (p < 0.01). The median level of lung MDA was significantly higher in the hyperoxia group compared with the control group (p < 0.05) and the colchicine-treated group (p < 0.05). Lung homogenate SOD and GSH-Px activities in the colchicine-treated group were significantly higher than in the hyperoxia group (p < 0.05). Furthermore, colchicine-treated pups had lower lung homogenate TNF-alpha and IL-1 beta levels compared with the hyperoxia group (p < 0.05). Conclusions: Colchicine has favorable effects on alveolarization as well as inflammation and oxidative stress markers in an animal model of BPD. Copyright (C) 2012 S. Karger AG, BaselÖğe Comparison of Three Different Administration Positions for Intratracheal Beractant in Preterm Newborns with Respiratory Distress Syndrome(Elsevier Taiwan, 2016) Karadag, Ahmet; Ozdemir, Ramazan; Degirmencioglu, Halil; Uras, Nurdan; Dilmen, Ugur; Bilgili, Gokmen; Erdeve, OmerBackground: The aim of this study was to compare the efficacy and adverse effects of various intratracheal beractant administration positions in preterm newborns with respiratory distress syndrome. Methods: This study was performed on preterm newborns with respiratory distress syndrome. The inclusion criteria were being between 26 weeks and 32 weeks of gestational age, having a birth weight between 600 g and 1500 g, having received clinical and radiological confirmation for the diagnosis of respiratory distress syndrome (RDS) within 3 hours of life, having been born in one of the centers where the study was carried out, and having fractions of inspired oxygen (FiO(2)) >= 0.40 to maintain oxygen saturation by pulse oximeter at 88-96%. Beractant was administered in four positions to Group I newborns, in two positions to Group II, and in neutral position to Group III. Results: Groups I and II consisted of 42 preterm infants in each whereas Group III included 41 preterm infants. No significant differences were detected among the groups with regards to maternal and neonatal risk factors. Groups were also similar in terms of the following complications: patent ductus arteriosus (PDA), pneumothorax, intraventricular hemorrhage (IVH), chronic lung disease (CLD), retinopathy of prematurity (ROP), necrotising enterocolitis (NEC), death within the first 3 days of life, death within the first 28 days of life, and rehospitalization within 1 month after discharge. Neither any statistically significant differences among the parameters related with surfactant administration, nor any significant statistical differences among the FiO(2) levels and the saturation levels before and after the first surfactant administration among the groups were determined. Conclusion: In terms of efficacy and side effects, no important difference was observed between the recommended four position beractant application, the two position administration, and the neutral position. Copyright (C) 2016, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. All rights reserved.Öğe Early regular versus late selective poractant treatment in preterm infants born between 25 and 30 gestational weeks: a prospective randomized multicenter study(Taylor & Francis Ltd, 2014) Dilmen, Ugur; Ozdemir, Ramazan; Aksoy, Hatice Tatar; Uras, Nurdan; Demirel, Nihal; Kirimi, Ercan; Erdeve, OmerObjective: Surfactant treatment in the early hours of life significantly decreases the rates of death and air leak, and increases survival without bronchopulmonary dysplasia (BPD) in preterm infants. We aimed to compare the impact of early surfactant (ES) administration to late selective (LS) treatment on neonatal outcomes in preterm infants. Methods: All preterm infants between 25 and 30 wks gestational age and who were not entubated in the delivery room and did not have any major congenital malformation or perinatal asphyxia were randomized to ES treatment (200 mg/kg Curosurf (R) administration in 1 hour after birth) or LS treatment (200 mg/kg Curosurf (R) administration in the first 6 h of life if needed). The patients were treated by nasal continuous positive airway pressure (nCPAP) treatment regardless of the surfactant requirement. Outcomes were the necessity of mechanical ventilation, nCPAP duration, the oxygen requirement duration, the rates of BPD, retinopathy of prematurity (ROP) and mortality, and the assesment of the following situations; (pneumothorax, patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), and intraventricular hemorrhage (IVH) >= grade III). Results: Among 159 infants enrolled in the study, 79 were randomized to ES and 80 to LS treatment groups. Thirty-five patients (44%) in the LS treatment group needed surfactant administration. Necessity of second dose surfactant administration was 8.9% in the ES treatment group. Although necessity of mechanical ventilation, nCPAP duration, oxygen need duration, rates of PDA, NEC, BPD, ROP stage >3 and mortality did not show a significant difference between groups, the ES treatment group had lower rates of pneumothorax and IVH >= grade III when compared to the LS treatment group. Conclusions: ES treatment decreases IVH (>= grade III) and pneumothorax rates but does not have any effect on BPD when compared to LS.Öğe Is Folic Acid Supplementation Really Necessary in Preterm Infants ?32 Weeks of Gestation?(Lippincott Williams & Wilkins, 2014) Oncel, Mehmet Yekta; Calisici, Erhan; Ozdemir, Ramazan; Yurttutan, Sadik; Erdeve, Omer; Karahan, Sevilay; Dilmen, UgurObjectives: The aim of this study was to define whether there was folate deficiency in hospitalized preterm infants, and, second, to define the effect of feeding modalities on serum folate levels. Methods: Infants born <= 32 weeks of gestation were included in the study. Blood samples for the determination of serum folate levels were obtained on days 14 and 28 postnatally, as well as 36 weeks postconceptionally (or just before discharge if patients are discharged <36 weeks)-samples A, B, and C, respectively. Infants were divided into 3 groups based on mode of feeding; human breast milk (HBM), fortified HBM (fHBM), or preterm formula (PF). Results: A total of 162 preterm infants were enrolled: 17 (10.5%) of whom received HBM alone, 94 (58%) received fHBM, and 51 (31.5%) were fed with PF. None of the preterm infants developed folate deficiency during the study period. Preterm infants in the fHBM and PF groups had significant higher serum folate levels in samples C when compared with those receiving HBM alone (P < 0.001 for both). Multivariate analysis to evaluate the effects of maternal supplementation, smoking habit, gestational age, birth weight, and cumulative folic acid intake in samples A, B, and C suggested that maternal smoking and maternal folic acid supplementation had significant effects on serum folate levels in sample A and B. Conclusions: Preterm infants receiving parenteral nutrition with high folic acid content have no risk of folate deficiency during the 2 months of age; however, preterm infants fed orally from birth with HBM or PF with a low folic acid content could be at risk for folate deficiency, especially when mothers are smokers and/or do not receive folic acid supplementation during pregnancy.Öğe Mean Platelet Volume in Neonatal Sepsis(Wiley, 2012) Oncel, Mehmet Yekta; Ozdemir, Ramazan; Yurttutan, Sadik; Canpolat, Fuat Emre; Erdeve, Omer; Oguz, Serife Suna; Uras, NurdanBackground The aim of this study was to investigate any changes in mean platelet volume (MPV) in patients with neonatal sepsis (NS). Methods Subjects were stratified into two groups: proven sepsis (Group 1a) and clinical sepsis (Group 1b). The control group (Group 2) consisted of healthy newborns matched for gestational age and birth weight. Results A total of 100 patients with NS (35 with proven sepsis and 65 with clinical sepsis) and 50 healthy controls were enrolled. A comparison of markers of sepsis obtained at baseline revealed white blood cell count (WBC), C-reactive protein (CRP), interleukin-6 (IL-6), and MPV levels to be significantly higher in newborns with sepsis compared to healthy controls (P = 0.01, <0.001, <0.001, and 0.001, respectively). Mean baseline serum levels of CRP and MPV were significantly higher in Group 1a compared to Group 1b (P = 0.003, P = 0.007, respectively), whereas the difference between group with regards to baseline serum levels of IL-6 and platelet count was statistically insignificant (P = 0.14, P = 0.28, respectively). Conclusion This is the first study to demonstrate a statistically significant difference with regard to baseline MPV values between patients with sepsis (proven or clinical) and healthy controls. J. Clin. Lab. Anal. 26:493-496, 2012. (C) 2012 Wiley Periodicals, Inc.Öğe An observational, multicenter, registry-based cohort study of Turkish Neonatal Society in neonates with Hypoxic ischemic encephalopathy(Public Library Science, 2023) Okulu, Emel; Hirfanoglu, Ibrahim Murat; Satar, Mehmet; Erdeve, Omer; Koc, Esin; Ozlu, Ferda; Gokce, MahmutBackground Hypoxic ischemic encephalopathy (HIE) is a significant cause of mortality and short- and long-term morbidities. Therapeutic hypothermia (TH) has been shown to be the standard care for HIE of infants >= 36 weeks gestational age (GA), as it has been demonstrated to reduce the rates of mortality, and adverse neurodevelopmental outcomes. This study aims to determine the incidence of HIE in our country, to assess the TH management in infants with HIE, and present short-term outcomes of these infants. Methods The Turkish Hypoxic Ischemic Encephalopathy Online Registry database was established for this multicenter, prospective, observational, nationally-based cohort study to evaluate the data of infants born at >= 34 weeks GA who displayed evidence of neonatal encephalopathy (NE) between March, 2020 and April 2022. Results The incidence of HIE among infants born at >= 36 weeks GA (n = 965) was 2.13 per 1000 live births (517:242440), and accounting for 1.55% (965:62062) of all neonatal intensive care unit admissions. The rates of mild, moderate and severe HIE were 25.5% (n = 246), 58.9% (n = 568), and 15.6% (n = 151), respectively. Infants with severe HIE had higher rates of abnormal magnetic resonance imaging (MRI) findings, and mortality (p<0.001). No significant difference in mortality and abnormal MRI results was found according to the time of TH initiation (<3 h, 3-6 h and >6 h) (p>0.05). TH was administered to 85 (34.5%) infants with mild HIE, and of those born of 34-35 weeks of GA, 67.4% (n = 31) received TH. A total of 58 (6%) deaths were reported with a higher mortality rate in infants born at 34-35 weeks of GA (OR 3.941, 95% Cl 1.446-10.7422, p = 0.007). Conclusion The incidence of HIE remained similar over time with a reduction in mortality rate. The timing of TH initiation, whether <3 or 3-6 h, did not result in lower occurrences of brain lesions on MRI or mortality. An increasing number of infants with mild HIE and late preterm infants with HIE are receiving TH; however, the indications for TH require further clarification. Longer follow-up studies are necessary for this vulnerable population.Öğe An observational, prospective, multicenter study on rescue high-frequency oscillatory ventilation in neonates failing with conventional ventilation(Public Library Science, 2019) Erdeve, Omer; Okulu, Emel; Tunc, Gaffari; Celik, Yalcin; Kayacan, Ugur; Cetinkaya, Merih; Buyukkale, GokhanBackground To achieve gas exchange goals and mitigate lung injury, infants who fail with conventional ventilation (CV) are generally switched to high-frequency oscillatory ventilation (HFOV). Although preferred in many neonatal intensive care units (NICUs), research on this type of rescue HFOV has not been reported recently. Methods An online registry database for a multicenter, prospective study was set to evaluate factors affecting the response of newborn infants to rescue HFOV treatment. The study population consisted of 372 infants with CV failure after at least 4 hours of treatment in 23 participating NICUs. Patients were grouped according to their final outcome as survived (Group S) or as died or received extracorporeal membrane oxygenation (ECMO) (Group D/E). Patients' demographic characteristics and underlying diseases in addition to their ventilator settings, arterial blood gas (ABG) analysis results at 0, 1, 4, and 24 hours, type of device, ventilation duration, and complications were compared between groups. Results HFOV as rescue treatment was successful in 58.1% of patients. Demographic and treatment parameters were not different between groups, except that infants in Group D/E had lower birthweight (BW) (1655 +/- 1091 vs. 1858 +/- 1027 g, p = 0.006), a higher initial FiO2 setting (83% vs. 72%, p < 0.001), and a higher rate of nitric oxide exposure (21.8% vs. 11.1%, p = 0.004) in comparison to infants who survived (Group S). The initial cut-offs for a successful response on ABG were defined as pH > 7.065 (OR: 19.74, 95% CI 4.83-80.6, p < 0.001), HCO3 > 16.35 mmol/L (OR: 1.06, 95% CI 1.01-1.1, p = 0.006), and lactate level < 3.75 mmol/L (OR: 1.09% 95 CI 1.01-1.16, p = 0.006). Rescue HFOV duration was associated with retinopathy of prematurity (p = 0.005) and moderate or severe chronic lung disease (p < 0.001), but not with patent ductus arteriosus or intraventricular hemorrhage, in survivors (p > 0.05). Conclusion Rescue HFOV as defined for this population was successful in more than half of the patients with CV failure. Although the response was not associated with gestational age, underlying disease, device used, or initial MV settings, it seemed to be more effective in patients with higher BW and those not requiring nitric oxide. Initial pH, HCO3, and lactate levels on ABG may be used as predictors of a response to rescue HFOV.Öğe An Observational, Prospective, Multicenter, Registry-Based Cohort Study Comparing Conservative and Medical Management for Patent Ductus Arteriosus(Frontiers Media Sa, 2020) Okulu, Emel; Erdeve, Omer; Arslan, Zehra; Demirel, Nihal; Kaya, Huseyin; Gokce, Ismail Kursad; Ertugrul, SabahattinNo consensus has been reached on which patent ductus arteriosus (PDAs) in preterm infants require treatment and if so, how, and when they should be treated. A prospective, multicenter, cohort study was conducted to compare the effects of conservative approaches and medical treatment options on ductal closure at discharge, surgical ligation, prematurity-related morbidities, and mortality. Infants between 24(0/7)and 28(6/7)weeks of gestation from 24 neonatal intensive care units were enrolled. Data on PDA management and patients' clinical characteristics were recorded prospectively. Patients with moderate-to-large PDA were compared. Among the 1,193 enrolled infants (26.7 +/- 1.4 weeks and 926 +/- 243 g), 649 (54%) had no or small PDA, whereas 544 (46%) had moderate-to-large PDA. One hundred thirty (24%) infants with moderate-to-large PDA were managed conservatively, in contrast to 414 (76%) who received medical treatment. Eighty (62%) of 130 infants who were managed conservatively did not receive any rescue treatment and the PDA closure rate was 53% at discharge. There were no differences in the rates of late-onset sepsis, necrotizing enterocolitis (NEC), retinopathy of prematurity, intraventricular hemorrhage (>= Grade 3), surgical ligation, and presence of PDA at discharge between conservatively-managed and medically-treated infants (p> 0.05). Multivariate analysis including perinatal factors showed that medical treatment was associated with increased risk for mortality (OR 1.68, 95% Cl 1.01-2.80,p= 0.046), but decreased risk for BPD or death (BPD/death) (OR 0.59, 95%Cl 0.37-0.92,p= 0.022). The preferred treatment options were ibuprofen (intravenous 36%, oral 31%), and paracetamol (intravenous 26%, oral 7%). Infants who were treated with oral paracetamol had higher rates of NEC and mortality in comparison to other treatment options. Infants treated before postnatal day 7 had higher rates of mortality and BPD/death than infants who were conservatively managed or treated beyond day 7 (p= 0.009 and 0.007, respectively). In preterm infants born at <29 weeks of gestation with moderate-to-large PDA, medical treatment did not show any reduction in the rates of open PDA at discharge, surgical or prematurity-related secondary outcomes. In addition to the high incidence of spontaneous closure of PDA in the first week of life, early treatment (<7 days) was associated with higher rates of mortality and BPD/death.Öğe The relationship between trough drug concentrations and ductal closure in preterm infants treated with three-dose-oral ibuprofen(Taylor & Francis Ltd, 2013) Yurttutan, Sadik; Erdeve, Omer; Oncel, Mehmet Yekta; Ozdemir, Ramazan; Dilmen, UgurThe aim of the present study was to characterize the pharmacokinetic profile of oral ibuprofen on consecutive 3 d by trough serum levels, and if possible to define a cut-off level for ductal closure in preterm infants. The study enrolled 20 preterm infants with gestational age <= 30 weeks, birth weight <1250 g and hemodynamically significant patent ductus arteriosus (hsPDA). Patients received oral ibuprofen at an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 h. Patients were compared for serum ibuprofen levels in addition to their demographic and clinical data in case of their response to the treatment. hsPDA closed in 16 (80%) of the patients. Although mean ibuprofen levels on consecutive 3 d showed a plateau in general, ibuprofen serum levels on the first treatment day were statistically low in patients with unclosed hsPDA (p = 0.003). The optimal cut-off value for serum ibuprofen level on the first treatment day was measured as 5.5 mg/l with 100% sensitivity and 93% specificity. Serum ibuprofen level on the first treatment day seems to be an important factor for a successful ductal closure. Target concentration approach by the evaluation of trough level may be applicable to real-time dosing strategy.
