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Objective: To evaluate the efficacy of the MRI-based texture analysis (TA) of the basal ganglia and thalami to distinguish moderate-to-severe hypoxic-ischemic encephalopathy (HIE) from mild HIE in neonates. Methods: This study included 68 neonates (15 with mild, 20 with moderate-to-severe HIE, and 33 control) were born at 37 gestational weeks or later and underwent MRI in first 10 days after birth. The basal ganglia and thalami were delineated for TA on the apparent diffusion coefficient (ADC) maps, T1-, and T2 weighted images. The basal ganglia, thalami, and the posterior limb of the internal capsule (PLIC) were also evaluated visually on diffusion-weighted imaging and T1 weighted sequence. Receiver operating characteristic curve and logistic regression analyses were used. Results: Totally, 56 texture features for the basal ganglia and 46 features for the thalami were significantly different between the HIE groups on the ADC maps, T2-, and T2 weighted sequences. Using a Histogram_entropy log-10 value as >1.8 from the basal ganglia on the ADC maps (p < 0.001; OR, 266) and the absence of hyperintensity of the PLIC on T1 weighted images (p = 0.012; OR, 17.11) were found as independent predictors for moderate-to-severe HIE. Using only a Histogram_entropy log-10 value had an equal diagnostic yield when compared to its combination with other texture features and imaging findings. Conclusion: The Histogram_entropy log-10 value can be used as an indicator to differentiate from moderate-to-severe to mild HIE. Advances in knowledge: MRI-based TA may provide quantitative findings to indicate different stages in neonates with perinatal asphyxia.

Dear editor,Thanks for authors for their interest to our study titled "Comparison of Isotonic and Hypotonic Intravenous Fluids in Term Newborns: Is It Time to Quit Hypotonic Fluids?" [1]. By this w...

Amaç: Perinatal dönemde gebelerde saptanan yeni korona virüs (SARS-CoV2) ve neden olduğu hastalığın (COVID-19) yenidoğan bebeğe etkileri henüzkesinlik kazanmamıştır. Bu olgu serisi, ülkemizde pandeminin başlangıcındanbugüne dek, Dokuz Eylül Üniversitesi Hastanesinde, COVID-19 ile ilişkiligebeler ve bebeklerindeki klinik deneyimimizi paylaşmaktadır.Gereç ve Yöntem: Mart 2020 – Şubat 2021 tarihleri arasında planlı doğum veyaspontan başlayan doğum eylemi nedeniyle Dokuz Eylül ÜniversitesiHastanesine başvuran, nazofarengeal sürüntü örneklerinde SARS-CoV-2pozitifliği saptanan, birinde ikiz gebelik olan, toplam 12 gebe ve 13 bebekdeğerlendirilmiştir.Bulgular: Yenidoğan yoğun bakımda takip edilen bu bebeklerin takipleriboyunca, COVID-19 ile ilişkili bir semptomları gelişmemiş; kord kanı,amniyon sıvısı, anne sütü ve nazofarengeal sürüntü örneklerinde viral RNAsaptanmamıştır. Değerlendirilen plasenta patolojilerinin altısında (%60)maternal vasküler malperfüzyon saptanmıştır.Sonuç: Mevcut klinik sonuçlarımız perinatal COVID-19 enfeksiyonundaasemptomatik veya hafif semptomlu vakalarda vertikal geçişin düşükolasılıklı olduğunu, postnatal dönemde uygun koruyucu ekipmankullanımının ve temas önlemlerinin bebeğe intrapartum ve postpartum bulaşıazaltmada oldukça önemli olduğunu desteklemektedir.&nbsp

Aim We aimed to determine the current factors affecting the development of omphalitis in our region. Materials and methods This prospective case-control study included term and late preterm newborns admitted to the newborn outpatient clinic or paediatric emergency service between 2014 and 2015. One hundred newborns with omphalitis and age-matched 100 newborns as a control group were included. The perinatal, postnatal, and sociocultural characteristics of newborns were evaluated and the factors that could influence the development of omphalitis were determined. Results Younger maternal age and primiparity, lower maternal education, and lower maternal hand washing habits were the significant risk factors of omphalitis development. Using non-cotton clothes were the most important risk factor amongst all factors as it increases the omphalitis risk up to 13 times. The frequency of omphalitis was significantly higher in warm months when microorganisms were able to colonise and reproduce compared with the colder months. Conclusion Results suggested that community-based interventions promoting the improvement of neonatal care should emphasise simple and low-cost interventions such as hand washing habit of mothers, caring for the umbilical cord, and using cotton clothes for babies. This study also confirms the safety of dry cord care at the time of birth and afterwards. However, broadscale multicentric studies are needed to protect against omphalitis.

Acute respiratory distress syndrome (ARDS) is a clinical condition characterized by acute diffuse inflammatory lung injury and severe hypoxemia. In 2017, the Montreux Consensus defined diagnostic criteria for ARDS in the neonatal period. The management of ARDS includes strict adherence to lung-protective ventilation strategies and therapeutic agents to improve gas exchange. We report two similar cases of premature infants with gestational ages of 23 and 24 weeks diagnosed with neonatal ARDS according to the Montreux definition. These patients developed acute worsening of oxygenation on the 30th and 28th day of life, respectively, while they were ventilated on volume-guarantee assist/control mode. Chest X-rays revealed bilateral diffuse opacity, there were no cardiogenic origins for pulmonary edema, and their oxygenation indexes were >8. Both cases fulfilled the neonatal ARDS criteria and the patients' clinical conditions were associated with late onset neonatal sepsis. After lung recruitment maneuver, the infants began HFO volume-guarantee ventilation and received surfactant treatment. Since they showed a poor short-term response, intratracheal surfactant of 100 mg/kg plus budesonide of 0.25 mg/kg were administered and their oxygenation indexes were reduced stepwise. Both patients survived and were discharged home with spontaneous breathing of room air. Neonatal ARDS is generally an underdiagnosed condition associated with sepsis, pneumonia, and meconium aspiration. Impaired surfactant activity and reduced lung compliance play important roles in its pathophysiology. To our knowledge, this is the first case report indicating the possible therapeutic role of budesonide plus surfactant in ARDS treatment. Since ARDS is an entity not recognized in newborns, we want to emphasize neonatal ARDS diagnosis and underline that the combination of budesonide and surfactant may be a novel therapeutic option in the treatment of ARDS.

Objective: Hypotonic fluids have been traditionally used in newborns. National Institute for Health and Clinical Excellence-2015 (NICE) fluid therapy guideline recommends the use of isotonic fluids as maintenance fluid therapy in term newborns. However, there is no clear evidence supporting this recommendation. This study aims to compare isotonic (5% dextrose in 0.9% sodium chloride (NaCl)) and hypotonic (5% dextrose in 0.45% NaCl) parenteral fluid therapies in hospitalized term newborns with regard to changes in plasma Na (pNa) and complications related with fluid therapy. Methods: This was a retrospective cohort study performed in a tertiary university hospital NICU between January 2016 and April 2018. Term newborns who were initially isonatremic or mildly dysnatremic (pNa 155 meq/L) and receiving fluid therapy for maintenance or replacement therapy after 48th postnatal hours were eligible for the study. Infants having specific diagnoses requiring extraordinary fluids were excluded. The primary outcome evaluated was the change in mean plasma Na (Delta pNa meq/L/h) at 24 h or at the end of intravenous (i.v.) fluid therapy. Secondary outcomes evaluated were the risk of hyponatremia, hypernatremia, and adverse events attributable to fluid administration. Results: Among the 108 included newborns, 57 received hypotonic fluid (5% dextrose solution in 0.45% NaCl) and the remaining received isotonic fluid (5% dextrose solution in 0.9% NaCl) therapy. The hypotonic fluid group showed a greater Delta pNa compared to the isotonic group (0.48 +/- 0.28 vs. 0.27 +/- 0.21 meq/L/h, p = .001). The risk of experiencing unsafe plasma Na decrease in the hypotonic fluid group (Delta pNa >0.5 meq/L/h) was higher than the isotonic fluid group (odd ratio: 8.46; 95% confidence interval (CI): 2.3-30.06). Six mildly hypernatremic babies between 48 and 72 h of postnatal age showed insufficient Na reduction despite the appropriate amount of fluid. No significant difference was found between the two groups in terms of other outcomes. Conclusion: The results of this study suggested that as maintenance or replacement fluid therapy in the newborn, hypotonic fluids, even 5% dextrose in 0.45% NaCl, can lead to unsafe plasma Na decreases in term newborns, while isotonic fluids are safe when started after the first few days of life. Although the results parallel NICE guidelines, before making recommendations regarding the removal of hypotonic fluids entirely from clinical practice in term newborns following the renal adaptation period; larger randomized controlled studies involving a wide range of babies are needed.

High frequency oscillatory ventilation with volume-guarantee (HFOV-VG) is a promising lung protective ventilator mode for the treatment of respiratory failure in newborns. However, indicators of optimal ventilation during HFOV-VG mode are not identified yet. In this study, we aimed to evaluate optimal high-frequency tidal volume (VThf) and the dissociation coefficient of CO2 (DCO2) levels to achieve normocapnia during HFOV-VG after lung recruitment in very low birthweight infants with respiratory distress syndrome (RDS). Preterm babies under the 32nd postmenstrual week with severe RDS that received HFOV-VG using open-lung strategy between January 2014 and January 2019 were retrospectively evaluated. All included patients were treated with the Drager Babylog VN500 ventilator in the HFOV-VG mode. In total, 53 infants with a mean gestational age of 26.8 +/- 2.3 weeks were evaluated. HFOV mean optimal airway pressure (MAPhf) level after lung recruitment was found to be 10.2 +/- 1.7 mbar. Overall, the mean applied VThf per kg was 1.64 +/- 0.25 mL/kg in the study sample. To provide normocapnia, the mean VThf was 1.61 +/- 0.25 mL/kg and the mean DCO(2)corr was 29.84 +/- 7.88 [mL/kg](2)/s. No significant correlation was found between pCO(2) levels with VThf (per kg) or DCO(2)corr levels. VThf levels to maintain normocarbia were significantly lower with 12 Hz frequency compared to 10 Hz frequency (1.50 +/- 0.24 vs. 1.65 +/- 0.25 mL/ kg, p < 0.001, respectively). A weak but significant positive correlation was found between mean airway pressure (MAPhf) and VThf levels. To our knowledge, this is the largest study to evaluate the optimal HFOV-VG settings in premature infants with RDS, using the open-lung strategy. According to the results, a specific set of numbers could not be recommended to achieve normocarbia. Following the trend of each patient and small adjustments according to the closely monitored pCO(2) levels seems logical.

Objectives Cholestasis is a common disease of the liver in premature infants and no specific preventive treatment is currently available. Fucose, one of the monosaccharide building blocks of human milk oligosaccharides, may prevent cholestatic hepatic injury by various mechanisms. The aim of this study was to investigate the protective effect of fucose treatment after endotoxin-induced cholestasis in a rat model. Methods Wistar rat pups were divided into four groups as: group I, control group; group II, fucose-supplemented group; group III, lipopolysaccharide (LPS)-administered group, and group IV, LPS-exposed and fucose-supplemented group. Fucose was given 100 mg/kg i.p. every other day between PN5–17. LPS was administered on PN19 to establish endotoxin-induced cholestasis model. On PN21, animals were sacrificed to evaluate liver cell damage and apoptosis. Results Fucose supplementation significantly improved the biochemical parameters that deteriorated in LPS-administered group, significantly increased the expression of bile salt export pump, reduced the number of apoptotic cell death, and greatly prevented LPS-induced cholestatic hepatic injury. Conclusion Given our results, fucose may be useful in reducing hepatic injury and might possess clinical relevance for the preventive treatment of inflammation-induced cholestatic injury in newborns.

Objective: Maternal folic acid supplementation has been recommended prior to and during the first trimester of pregnancy to reduce the risk of infant neural tube defects. However, an uncertain relationship between folic acid supplementation during pregnancy and development of childhood asthma exists. Recent data show a methyl donor-rich diet could increase the risk of developing allergic airway disease through DNA methylation and aberrant gene transcription. This study evaluated the effect of folic acid supplementation during pregnancy on airway remodeling and allergic airway disease vulnerability in a mouse asthma model.Methods: BALB/c mice were divided into four groups according to gestational folic acid supplementation and postnatal ovalbumin (OVA) exposure: Group 1 (whole pregnancy folic acid supplementation+OVA-exposed group), Group 2 (first gestational week folic acid supplementation+OVA-exposed group), Group 3 (no folic acid supplementation+OVA-exposed group), and Group 4 (control group). Offspring were sacrificed on day 45 for immunohistological and ultrastructural tests.Results: In OVA challenged groups, folic acid supplementation led to a thicker epithelial and subepithelial smooth muscle layer than in the unsupplemented group. Moreover, folic acid supplementation during whole pregnancy (Group 1) was associated with a thicker epithelial and subepithelial smooth muscle layer than folic acid supplementation during the first week of pregnancy (Group 2), suggesting a duration-response relationship. Electron microscopic imaging revealed that structural changes including the loss of epithelial integrity, thickening of basement membrane, and subepithelial fibrosis were more prominent in the folic acid supplementation groups.Conclusions: This study suggested that maternal folic acid supplementation during pregnancy affects airway remodeling and increases the allergic responses induced by ovalbumin challenge in offspring. In addition, the effect size increased as the duration and cumulative dose increased.

Beken, Serdar/0000-0002-8609-2684; BAS, AHMET YAGMUR/0000-0002-1329-2167; Bulbul, Ali/0000-0002-3510-3056; Karatekin, Guner/0000-0001-7112-0323, WOS: 000534242500056, PubMed: 31851725, Objective To investigate the early neonatal outcomes of very-low-birth-weight (VLBW) infants discharged home from neonatal intensive care units (NICUs) in Turkey. Material and methods A prospective cohort study was performed between April 1, 2016 and April 30, 2017. the study included VLBW infants admitted to level III NICUs. Perinatal and neonatal data of all infants born with a birth weight of.1500 g were collected for infants who survived. Results Data from 69 NICUs were obtained. the mean birth weight and gestational age were 1137 +/- 245 g and 29 +/- 2.4 weeks, respectively. During the study period, 78% of VLBW infants survived to discharge and 48% of survived infants had no major neonatal morbidity. VLBW infants who survived were evaluated in terms of major morbidities: bronchopulmonary dysplasia was detected in 23.7% of infants, necrotizing enterocolitis in 9.1%, blood culture proven late-onset sepsis (LOS) in 21.1%, blood culture negative LOS in 21.3%, severe intraventricular hemorrhage in 5.4% and severe retinopathy of prematurity in 11.1%. Hemodynamically significant patent ductus arteriosus was diagnosed in 24.8% of infants. Antenatal steroids were administered to 42.9% of mothers. Conclusion the present investigation is the first multicenter study to include epidemiological information on VLBW infants in Turkey. Morbidity rate in VLBW infants is a serious concern and higher than those in developed countries. Implementation of oxygen therapy with appropriate monitoring, better antenatal and neonatal care and control of sepsis may reduce the prevalence of neonatal morbidities. Therefore, monitoring standards of neonatal care and implementing quality improvement projects across the country are essential for improving neonatal outcomes in Turkish NICUs., Turkish Neonatal Society [2-2016]; Turkish Neonatal Society, This study was supported by the Turkish Neonatal Society, http://www.neonatology.org.tr, number 2-2016, received by AYB. Turkish Neonatal Society funded the study's online registry system. the funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Periventricular leukomalacia (PVL) is the leading cause of neurocognitive deficits in children with prematurity. We previously hypothesized that surfactant protein D (SPD) with its ability to bind toll-like receptors may have a possible ameliorating effect in PVL.Three groups were defined as: LPS-administered and postnatal intranasal saline administered group, LPS-administered and postnatal intranasal SPD-treated group, and control group. Twenty-eight offspring rats were reared with their dams until their sacrifice for histological evaluation on day 7.A significant loss of brain weight occurred in the LPS group compared with controls. The postnatal intranasal SPD treatment significantly reduced the number of TUNEL-positive cells in the periventricular white matter as compared with the LPS-treated group. Compared with the control group, LPS injection in the rat brain significantly reduced the MBP-positive staining. Postnatal SPD treatment greatly prevented LPS-stimulated loss of MBP staining.Present study demonstrated a neuroprotective effect of SPD in a rat model of PVL. Our results offer future implications towards increasing our understanding about multifactorial mechanisms underlying periventricular leukomalacia and developing plausible therapeutic strategies in order to prevent neurocognitive deficits in preterm infants.

A growing body of evidence suggests that vaccinations play a role in the normal maturation of the immune system and in both the development and balance of immune regulatory pathways that can impact health later in life. This study aimed to evaluate the effects of Bacillus Calmette-Guerín (BCG) vaccine on the hyperoxia-induced neonatal rat lung injury.Four groups were defined as hyperoxia-exposed BCG-vaccinated, hyperoxia-exposed placebo, room air-exposed control and room air-exposed BCG-vaccinated group. The validity of the hyperoxia-induced lung injury model used in this study was confirmed by histological and immunohistochemical test. Gene expression related with cytokine and growth factor was evaluated by real-time reverse transcription polymerase chain reaction.The mean alveolar surface area and quantification of secondary crest formation in the oxygen-exposed placebo group was significantly lower than that of the oxygen-exposed BCG-vaccinated group. Compared to the oxygen-exposed placebo group, the oxygen-exposed BCG-vaccinated group showed a significantly decreased alveolar septal fibrosis and smooth muscle actin expression. The expression of genes VEGF, FGF-BP1, IL-13, and NFκB1 (p50) in the lungs of the hyperoxia-exposed BCG-vaccinated group was significantly higher than that of the hyperoxia-exposed placebo group.Results suggest that BCG vaccination can protect against neonatal hyperoxic lung injury. These benefits may be interpreted to coincide with its immunomodulatory effects on pro-inflammatory and anti-inflammatory cytokine balance and expression of growth factors.

Aim: This study aimed to compare the recently published prescriptive INTERGROWTH-21st standards with commonly used intrauterine based Fenton growth standards in terms of birth size classification and extrauterine growth restriction (EUGR) incidence in a sample of very preterm infants.Methods: The anthropometric measures of preterm infants born before 32weeks of gestation at the Dokuz Eylul University Hospital during the period from January 2012 to February 2016 were obtained at birth, at the 36th gestational weeks or at the time of discharge. Birth and growth data were presented as percentiles according to the two reference standards.Results: A total of 248 infants with mean gestational age of 29.12.1weeks were included. The small for gestational age (SGA) rate was significantly higher (12 versus 15%, p=.004) and the EUGR rate was significantly lower (40.2 versus 31.5%, p

Objective: Excess glucocorticoid (GC) exposure on the fetal brain during critical stages of development has considerable effects on the development of the central nervous system (CNS). This study thus aimed to evaluate the differential effects of GC exposure on critical growth factor levels during different stages of brain maturation.Methods: For this purpose, forty-two rat pups were divided into six groups based on the timing of betamethasone administration. Rats in the treatment groups were exposed to intraperitoneal betamethasone injections beginning at different time points (postnatal days 1, 2, and 3). Rats in the placebo group received the same volume of 0.9% saline via the same fashion. Pups were sacrificed at 24h following the final injection for determining the neuronal density and immunohistochemical evaluation of critical growth factors.Results: In the groups treated with betamethasone on postnatal day 1 (P1) and P2, which correspond to 22-24 and 24-28 gestational weeks in humans, the neuronal count in the hippocampal regions was significantly lower than their control groups. However, if steroid therapy was administered on P3, corresponding to 28-32 weeks in humans, no difference was observed between the two groups. Growth factors were affected in different ways depending on the steroid administration time and evaluated region.Conclusions: The results suggest that the modulating effect of steroids on neuron count and growth factor response depends on the stage of brain development at the time of exposure. Therefore, this may be one of the key determinants affecting the deleterious and beneficial effects of GCs on the CNS.

BackgroundCurrently, there is a lack of clear definition for neonatal sepsis. The Pediatric Committee of the European Medicines Agency (EMA) developed consensus criteria to ensure a standardization for neonatal sepsis definition. However, there is no evidence supporting the accuracy of the EMA sepsis criteria in neonatal sepsis diagnosis. The main objective of this study was to evaluate the diagnostic accuracy of EMA sepsis criteria for proven neonatal sepsis.MethodsA multicenter prospective cohort study was conducted from October 2015 to November 2018. Infants with a gestational age over 34th weeks, diagnosed with clinical sepsis and received antibiotics according to the EMA criteria or experienced neonatologists' opinion were included. Blood culture or multiplex real time-PCR or 16S-rRNA positive infants were accepted as "proven sepsis". The predictive performance of EMA criteria for proven sepsis was evaluated by sensitivity, specificity, accuracy, and area under the curve measures of receiver operator characteristic curves. Data-mining methods were used for further analysis.ResultsAmong the 245 included infants, the EMA criteria were positive in 97 infants (39.6%), while proven sepsis was diagnosed in 113 infants (46.1%). The sensitivity, specificity, and accuracy of the EMA criteria for proven sepsis were 44.2% (95%CI: 34.9-53.9), 64.4% (95%CI: 55.6-72.5), 55.1% (95%CI: 46.6-59.4) respectively. None of the clinical and laboratory parameters had sufficient performance individually in terms of sensitivity, specificity and accuracy measures. The diagnostic performance was similar when different clinical findings were added to the EMA sepsis criteria or assessment of the score was interpreted in different ways.ConclusionsResults highlighted that clinician opinion and standard laboratory tests are limited in the neonatal sepsis diagnosis. The EMA criteria also did not efficiently meet the diagnostic accuracy measures for neonatal sepsis. A predictive sepsis definition and rapid bedside point-of care tests are urgently needed.

Recent data suggest that induced hypothermia has some protective effects on experimental lung injury. We aimed to evaluate the protective effect of mild hypothermia in a rat model of lipopolysaccharide (LPS) induced neonatal lung injury.Wistar rat pups were divided into four groups, specifically: (i) A control group, with no LPS administration and maintained in room air; (ii) A LPS group, with antenatal LPS administrated and maintained in room air; (iii) A LPS + hypothermia group, with antenatal LPS administrated and exposed to hypothermia; (iv) A hypothermia group, with no LPS administration and exposed to hypothermia. Intraperitoneal LPS was injected into maternal rats at the 19th and 20th gestational days to establish a neonatal lung injury model. Mild hypothermia was started at the postnatal 24th hour and continued during 24 h. At the postnatal 7th day, the rats were sacrificed and lung samples were evaluated for immunohistochemical tests and proinflammatory gene expression levels.Hypothermia therapy attenuated the damaging effects of antenatal LPS administration. Furthermore, hypothermia therapy reduced gene expression of pro-inflammatory cytokines (IL-6, IL-1α, IL-1β, TNF-α) and induced the expression of a potent anti-inflammatory cytokine (IL-10).The results of this study indicated that mild hypothermia therapy is effective in an LPS induced neonatal lung injury model. If these results are supported by further studies, hypothermia may also be a new therapy option for preventing bronchopulmonary dysplasia.

Hypoxia-ischemia is a major cause of perinatal brain injury in the newborn. Neotrofin, a neurotrophin agonist, has been shown to provide neuroprotection in several in vivo and in vitro studies. The aim of this study is to investigate the neuroprotective and ameliorating effects of neotrofin treatment after hypoxic-ischemic-injury-induced neuronal cell death, apoptosis in a neonatal hypoxic-ischemic brain injury rat model. Twenty-one seven-day-old Wistar rat pups were used in this study. The groups were: (1) a neotrofin-treated hypoxic-ischemic-group, (2) a saline-treated hypoxic-ischemic-group, and (3) a sham-operated group. Rat pups were subjected to left carotid artery occlusion followed by 2.5 h of hypoxic exposure. After the hypoxic exposure, group one received an intra-peritoneal injection of neotrofin at a dose of 60 mg/kg. Forty-eight hours after hypoxia, the animals were killed for histopathological evaluation to detect apoptosis and density of neurons. We found that neotrofin attenuates hypoxia-ischemia induced with neuronal density of the hippocampus, the prefrontal and the parietal cortex, and decreased apoptotic cell index in the same regions. Given our results, neotrofin may be useful in reducing brain injury: it possesses clinical relevance for the treatment of hypoxic-ischemic encephalopathy in the newborn. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Objectives: Periventricular leukomalacia (PVL) is the predominant form of brain injury in premature infants, and no specific treatment currently exists for this condition. We have evaluated whether maternal omega-3 fatty acid (omega 3 FA) treatment reduces endotoxin-induced PVL in the developing rat brain. Methods: Wistar rats with dated pregnancies were fed a standard diet or a diet enriched in omega 3 FA (70% docosahexaenoic acid + 30% eicosapentaenoic acid mixture) during gestation. Intraperitoneal injection of lipopolysaccharide (LPS) was administered consecutively on the 18th and 19th embryonic days to establish the endotoxin-induced PVL rat model. The animals were divided into four groups: (i) control, (ii) PVL, (iii) PVL+low-dose omega 3 FA and (iv) PVL+high-dose omega 3 FA. At day P7, apoptosis and hypomyelination in periventricular white matter were evaluated by immunohistochemical assessments. Results: High-dose maternal omega 3 FA treatment reduced brain weight loss. Maternal omega 3 FA treatment given either in low or high doses greatly decreased caspase-3 immunoreactivity and increased myelin basic protein immunoreactivity, indicating a decrease in apoptosis and hypomyelination. Conclusion: Considering that no specific treatment is available for PVL, maternal omega 3 FA supplementation may provide a nutritional strategy to limit periventricular white matter damage caused by infections during pregnancy.

Over the last decade, neuroprotective effects of erythropoietin (Epo) and its underlying mechanisms in terms of signal transduction pathways have been defined and there is a growing interest in the potential therapeutic use of Epo for neuroprotection. Several mechanisms by which Epo provides neuroprotection are recognized. In this review, we focused on the neuroprotective mechanisms of Epo and provide a short overview on both experimental and clinical studies, testing Epo as a neuroprotective agent in the neonatal brain injury, and the safety concerns with the clinical use of Epo treatment in neonates. (C) 2010 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Background: High-frequency oscillatory ventilation (HFOV) with volume guarantee (VG) is a new ventilation mode that allows the clinician to set a mean tidal volume to be delivered. Objective: This study aimed to investigate whether HFOV with a VG option may result in constant tidal volume delivery and less fluctuant CO2 levels compared to HFOV alone in premature infants with respiratory distress syndrome (RDS). Methods: Inborn infants at less than 32 weeks of gestation with RDS requiring invasive mechanical ventilation were eligible. Patients were randomized to receive HFOV + VG or HFOV alone as the initial ventilator mode and then crossed over to the other mode. HFOV was performed with ‘optimal lung volume strategy' during both of the periods. Results: Twenty infants were evaluated. The mean high-frequency tidal volume (VThf) and CO2 diffusion coefficient (DCO2) were significantly higher in the HFOV + VG mode than HFOV alone. HFOV + VG maintains VThf within the target range more consistently than HFOV. The incidences of hypocarbia and hypercarbia were lower in HFOV with VG than HFOV alone. Conclusion: This is the first prospective, randomized, short-term crossover clinical study that compared HFOV with and without VG in infants with acute RDS. Because of the lower VThf fluctuation and lower incidences of out-of-target PCO2 levels, HFOV combined with VG seems to be feasible for preterm infants. However, the results should be interpreted with caution due to the small sample size and short-term crossover design of the study.

To investigate the potential neuroprotective effect of maternal pentoxifylline (PNTX) treatment in endotoxin-induced periventricular leukomalasia (PVL) in the developing rat brain.Intraperitoneal injection of lipopolysaccharide was administered on two of three Wistar pregnant rats to establish PVL. To obtain PNTX-treated group, one of the two dams were injected with PNTX. The control group was treated with saline. Rat pups were grouped as control, maternal LPS-treated group and PNTX + LPS-treated group. At 7th postnatal days, apoptosis and hypomyelination were evaluated. Apoptosis was evaluated by caspase-3 and terminal deoxynucleotidyl transferase [TdT] dUTP nick endlabelling reaction (TUNEL) immunostaining. To assess hypomyelination, myelin basic protein (MBP) staining, as a marker of myelination, was evaluated.MBP staining was significantly less and weaker in the brains of the LPS-treated group as compared with the PNTX-treated group. PNTX treatment significantly reduced the number of apoptotic cells in the periventricular WM shown on Tunel and caspase-3.Presented study is first indicated that PNTX may provide protection against an LPS-induced inflammatory response and WMI in the developing rat brain. Our results also suggest that PNTX treatment in pregnant women with maternal or placental infection may minimize the risk of PVL and cerebral palsy.

DNA methylation and histone modifications are the most identified modifications that selectively activate or inactivate genes that control cell growth, proliferation, and apoptosis.We hypothesized that alterations in gene expression due to hypoxic-ischemic brain damage was regulated by epigenetic mechanisms including DNA methylation and histone methylation.To test this hypothesis, we established a rat model of HIE. Three groups were defined as hypoxic-ischemic, sham-operated, and control group.The validity of the HIE model used in this study was confirmed by histological and immunohistochemical tests. Gene expressions related with apoptosis and angiogenesis were studied at 0.5, 3, 6 and 24h after HI or sham operation. DNA and histone methylation status was studied in the genes showing significant change in expression.Most of the genes related with apoptosis and angiogenesis (Epo, Epor, Hif 1α, Hif3α, VEGFa, VEGFc, Casp1, Casp9, and Casp8ap2) induced early after HI (30min). All of these genes were unmethylated at the beginning of the insult and in the control group. DNA methylation percentage and histone methylation (H3K36) levels were not correlated with gen expression levels. To our knowledge this is the first study evaluating the role of epigenetic mechanisms in HIE model, therefore the absence of similar studies don't allow us to compare the present results. Further studies investigating different epigenetic mechanisms are needed.

Aim: Caffeine treatment reduces the frequency of apnoea of prematurity (AOP) and eliminates the need for mechanical ventilation by acting as a nonspecific inhibitor of adenosine A1 and adenosine 2A receptors. Patients with AOP have demonstrated variant responses to caffeine therapy. We proposed to investigate the role of A1 and 2A polymorphisms in the development of AOP and individual differences in caffeine response. Secondly, we aimed to determine whether these polymorphisms have any effect on bronchopulmonary dysplasia (BPD) development. Methods: Cord blood samples were collected from infants born with gestational ages between 24 and 34 weeks. Two groups were defined: patients without apnoea (n = 60) and patients with apnoea (n = 55). Patients with apnoea were divided into two subgroups: a caffeine-responsive group (n = 30) and an unresponsive group (n = 25). Six single-nucleotide polymorphisms were chosen for genotyping. Results: Patients with apnoea over 28 weeks of gestational age who responded to the caffeine treatment were found to carry the rs16851030 C/C genotype rather than the C/T or T/T genotype. Logistic regression analysis showed a significant correlation between rs35320474-C/T and T/T genotypes and apnoea and BPD development. Conclusion: Our results indicate a role for adenosine receptor gene polymorphisms in susceptibility to AOP and BPD and in interindividual variability to caffeine response.

Periventricular leukomalacia (PVL) is the dominant form of brain injury in premature infants and no specific treatment is currently available. Neotrofin, a neurotrophin agonist, has been shown to provide neuroprotection in several in vivo and in vitro studies. The aim of this study was to investigate the neuroprotective effect of neotrofin treatment after endotoxin induced PVL in a rat model. Wistar rat pups were divided into four groups as: (1) control, (2) lipopolysaccharide (LPS)-administered group, (3) LPS-administered and prenatal maternal neotrofin-treated group and (4) LPS-administered and postnatal neotrofin-treated group. Intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) was administered consecutively at the 18th and 19th embryonic days to establish endotoxin-induced PVL model. In the prenatal treatment group dams received an i.p. injection of neotrofin (60 mg/kg) following after the second LPS dose; and in the postnatal treatment group rat pups received i.p. injection of neotrofin (60 mg/kg) at birth. At P7, apoptosis and hypomyelination in periventricular white matter were evaluated by immunohistochemical assessments. The prenatal maternal neotrofin treatment significantly reduced the number of apoptotic cell death and greatly prevented LPS-stimulated loss of hypomyelinization. However, neotrofin treatment in the postnatal period was not as effective as intrauterine treatment. Given our results, neotrofin may be useful in reducing brain injury and possessing clinical relevance for the treatment of white matter injury in newborns. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

Background: Exposing the brain to a sub-damaging stimulus can protect against a subsequent lethal insult, a phenomenon termed preconditioning. The aim of this study was to investigate the neuroprotective effect of low dose LPS (lipopolysaccharide) pretreatment in endotoxin induced periventricular leukomalacia (PVL) in a rat model. Methods: Wistar rats with dated pregnancies were allocated to 5 groups: (i) no LPS administered, intraperitoneally (i.p.) pyrogen-free saline injected (Control group), (ii) 500 mu g/kg LPS administrated i.p. on days 18 and 19 (PVL group), (iii) 50 mu g/kg LPS administrated i.p. on day 17 followed by 500 mu g/kg LPS i.p. on days 18 and 19 (PC-PVL group), (iv) 50 mu g/kg LPS administrated on day 17 (PC only), and (v) i.p. pyrogen-free saline injected control group on day 17. Results: LPS-preconditioning given 24 h before potent LPS exposure significantly reduced the number of apoptotic cell deaths and prevented hypomyelination. Antioxidant enzyme gene expression levels (Superoxide Dismutase-SOD1, SOD2, and SOD3) were increased and Tumor Necrosis Factor (TNF)alpha expression levels were decreased in the PC+PVL group when compared with the PVL group. Conclusion: Low-dose LPS given one day before potent doses of LPS reduces antepartum LPS-induced brain damage. The mechanisms of protection might involve oxidation and inflammation. (C) 2012 Elsevier B.V. All rights reserved.

Supraphysiologic amounts of oxygen negatively influences brain maturation and development. The aim of the present study was to evaluate whether maternal omega-3 long-chain polyunsaturated fatty acid (omega-3 FA) supplementation during pregnancy protects the developing brain against hyperoxic injury. Thirty-six rat pups from six different dams were divided into six groups according to the diet modifications and hyperoxia exposure. The groups were: a control group (standard diet + room air), a hyperoxia group (standard diet + 80% O-2 exposure), a hyperoxia + high-dose omega-3 FA-supplemented group, a hyperoxia + low-dose omega-3 FA-supplemented group, a room air + low-dose omega-3 FA-supplemented + group, and a room air + high dose omega-3 FA-supplemented group. The omega-3 FA's were supplemented as a mixture of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) from the second day of pregnancy until birth. Rat pups in the hyperoxic groups were exposed to 80% oxygen from birth until postnatal day 5 (P5). At P5, all animals were sacrificed. Neuronal cell death and apoptosis were evaluated by cell count, TUNEL, and active Caspase-3 immunohistochemistry. Histopathological examination showed that maternally omega-3 FA deficient diet and postnatal hyperoxia exposure were associated with significantly lower neuronal counts and significantly higher apoptotic cell death in the selected brain regions. Omega-3 FA treatment significantly diminished apoptosis, in the selected brain regions, in a dose dependent manner. Our results suggest that the maternal omega-3 FA supply may protect the developing brain against hyperoxic injury. (C) 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

The aim of this randomized controlled trial was to assess whether the addition of volume guarantee (VG) to triggered ventilation decreases the duration of ventilation in very low birth weight (VLBW) infants with respiratory distress syndrome (RDS). Infants were randomized into two groups to initially receive either assist/control (A/C) or A/C plus VG ventilation and then weaned with synchronized intermittent mandatory ventilation (SIMV) or SIMV plus VG. Forty-five infants were included in the study. The demographic and clinical characteristics, values of tidal volume (VT), peak inspiratory pressure (PIP), fraction of inspired oxygen, carbon dioxide tension, and pH were similar for all participating infants initially. During the follow-up, the VT levels were more stable, and the PIP levels were significantly decreasing in the VG group. Although the duration of ventilation was shorter in the VG group, this trend was not statistically significant. The incidences of death and bronchopulmonary dysplasia (BPD) were not significantly different, but the combined outcome of death or BPD was lower in the VG group. Although the VG group experienced less frequent BPD, periventricular leukomalacia, and intraventricular hemorrhage, these differences were not statistically different. The VG option, when combined with A/C (in the acute phase of RDS) and SIMV (in the weaning), reduced VT variability, and may have shortened the duration of ventilation in VLBW infants. Overall mortality and BPD rates did not change, but their combined outcome was significantly improved in infants treated with VG modes as compared to those treated with synchronized pressure-limited modes alone.

WOS: 000296852300020, PubMed ID: 22004499

Aim Gastric aspiration is still applied in many centres during delivery room management of the newborn without any supporting evidence. We aimed to determine whether gastric aspiration affects vital signs, oxygenation, nutrition and short-term prognosis of the newborn. Method A total of 310 eligible healthy term newborns, identified from a total of 1300 live births, were randomly allocated to receive either gastric aspiration or standard care. During the first 20min, SpO 2 , heart rate, cyanosis and retraction scores were recorded once in a min; and blood pressure, respiration rate and neuroadaptive capacity were recorded once in every 5min. Information about nutrition and vomiting behaviours of the babies were taken from the mothers of the neonates on the postnatal 1st day at bedside and by a telephone call on the 7th day. Results No difference was determined between the groups in terms of 1st to 5thmin Apgar scores, attainment duration of SpO 2 to 85%, 92% and 95%, mean heart rate and respiration rate. Retraction frequency and mean systolic blood pressure of the 5th-min values were found to be significantly higher in the gastric aspiration group. There was no difference between the groups regarding breastfeeding starting time and vomiting frequency. Conclusion No positive effect of gastric aspiration in delivery room management of the newborn was observed. Conversely, the negative effects of gastric aspiration in neonates were observed with respect to physiological parameters. Our data suggest that gastric aspiration is not useful and may even be harmful in delivery room management of the healthy term newborns.

Carbon monoxide formed from the breakdown of heme to bilirubin is produced at a rate equal to the rate of bilirubin synthesis. During long-term clinical experiences we have observed that jaundiced newborns tend to steep more than the unjaundiced ones. There is no clear evidence about the role of endogenous CO in steep physiology, but increased CO production in jaundiced newborns probably plays rote in increased steep state due to the regulatory effects on steep circadian rhythm and REM-steep, via cholinergic system activation. (C) 2008 Elsevier Ltd. ALL rights reserved.

Introduction The aim of this study effects of BCG vaccine on the histopathologic and gene expression changes seen in hyperoxia induced neonatal rat lung injury. Method Twenty-three rat pubs were divided into four groups: air-exposed control group (n = 5), hyperoxia-exposed placebo group (n = 7), hyperoxia-exposed BCG-vaccinated group (n = 7), and air-exposed BCG-vaccinated group (n = 4). neonatal hyperoxic lung injury model was established according to the previous studies. Measurement of alveolar surface area, quantification of secondary crest formation, microvessel count, evaluation of alveolar septal fibrosis, and smooth muscle actin immunostaining were performed to assess hyperoxia-induced changes in lung morphology. The gene expression level was evaluated by RT-PCR. Results The alveolar surface areas were significant different between the oxygen exposed placebo group and oxygen exposed BCG vaccinated group (alveolar surface area; 0.29 ± 0.02 µm² and 0.52 ± 0.04 µm² p Conclusion Our results suggest that BCG vaccination can be a new protective strategy against neonatal hyperoxic lung injury. These benefical effects may be interpreted with its immunomodulatory effects on proinflammatory-antiinflammatory cytocin balance and expression of growth factors.

Hypoxic-ischemic brain injury is an important cause of neonatal mortality and subsequent serious neurological sequel. in neonatal brain the severity of hypoxic injury varies most probably due to the effects of multiple protective or deleterious factors. But the mechanisms under this difference are still not full understood. In recent years, some evidence has been found supporting the involvement of epigenetic mechanisms in many neurodegenerative diseases and stroke. We hypothesised that epigenetic mechanisms have been also involved in neonatal hypoxic-ischemic brain injury possibly by suppression of ischemia-induced cerebral inflammation and changing the expression of proapoptotic-antiapoptotic genes. (C) 2009 Elsevier Ltd. All rights reserved.