Search

Background. Hereditary bone marrow failure syndromes are a category of biologically different syndromes that can cause cytopenia in at least one hematopoietic cell lineage. Case. We present a 29-week-old male infant who had a low Apgar Score, advanced delivery room resuscitation, widespread petechial rash, and ecchymoses at birth, without any dysmorphic features. Initial laboratory tests revealed bicytopenia (platelet count 7x10 3 /uL, hemoglobin of 3.9 g/dL, neutrophil 2.0x103 /uL) with findings of disseminated intravasculer coagulation (DIC). Imaging studies demonstrated accompanying left-sided congenital pulmonary airway malformation. On the second postnatal week pancytopenia occurred and the bone marrow findings were consistent with congenital amegakaryocytic thrombocytopenia. Further evaluations for differential diagnosis of pancitopenia were performed and the results of congenital viral infections, metabolic and immunologic tests were negative. While supportive treatments were in progress, haploidentical bone marrow transplantation (BMT) was performed from the father at 84th day due to unavailability of HLA-matched relative or nonrelative donor. Whole exome sequencing revealed a novel heterozygous frameshift variation (c.1242dupT [p. Thr538fs]) in exon 8 of the MECOM gene and validated by Sanger sequencing. No variation was detected in the parents genetic analysis. Conclusions. In this report, we present a patient with congenital bone marrow failure successfully treated with haploidentic BMT and describe a novel, de novo pathogenic variant in MECOM gene. © 2022, Turkish National Pediatric Society. All rights reserved.

Both "new" and "old" bronchopulmonary dysplasia features overlap in preterm infants with severe bronchopulmonary dysplasia. The optimal ventilation strategy for infants with severe bronchopulmonary dysplasia has not been clarified yet. Principally, the lung is a multi-com- partmental heterogeneous tissue with regionally varying compliance and resistance. Generally, 2 critical strategical errors are common while ventilating infants with established bronchopulmonary dysplasia: (i) ventilatory management as if they are still in the acute phase of respiratory distress syndrome and (ii) early extubation attempts with the aim of reducing ventilator-induced lung injury. Considering the heterogeneous character of bronchopulmo- nary dysplasia, although there is no unique formulation for optimal ventilation, the most physi- ologically appropriate ventilation mode may be the combined mode of volume-guaranteed synchronized intermittent mechanical ventilation and pressure support ventilation. With the volume-guaranteed synchronized intermittent mechanical ventilation mode, slow compart- ments of the lung with high resistance and low compliance can be adequately ventilated, while fast compartments having relatively normal resistance and compliance can be venti- lated well with the pressure support ventilation mode. The following settings are advisable: frequency = 12-20 breaths per minute, tidal volume = 10-15 mL/min, positive end expiratory pressure = 7-12 cmH2O, and inspiratory to expiratory time ratio = 1 : 5. Higher oxygen satura- tions such as 92%-95% should be targeted to avoid subsequent pulmonary hypertension. In conclusion, there is no evidence-based ventilation recommendation for infants with severe bronchopulmonary dysplasia. However, given the changing pattern of the disease and the underlying pathophysiology, these infants should not be ventilated as if they were in the acute phase of respiratory distress syndrome.

Yenidoğulmuşlar: immun sistemlərinin yetkin olmaması, sübutu olmasa da anadan vertikal keçid ehtimalı, vaginal doğuş zamanı sidik və nəcis vasitəsilə perinatal təmas olma ehtimalı və asimptomatik yoluxmuş bir ana ilə doğuşdan sonra yaxın təmas səbəbiylə yüksək risk qrupundadır. Buna görə perinatal və neonatal dövrdə şübhəli və dəqiq hallar üçün uyğun bir yanaşma müvafiq şöbələrlə əməkdaşlıq etməklə edilməlidir. İnkubasiya müddəti ortalama 3-7 gün (min-max: 1-14 gün) olan infeksiyanın əsas yoluxma yolu damcı və təmas ilə olur. Fekal-oral ötürülməsini göstərən tədqiqatlar da mövcuddur. Kinik şəkli patoqnomonik deyildir: həyati əlamətlərdə dəyişikliklər (termolabillik, taxipnoe, taxikardiya), tənəffüs çətinliyi (xırıltı, burun pərlərinin gərginliyi, apnoe, öskürək), mədə-bağırsaq traktı əlamətləri (qusma, ishal, qarın distaniyası) və letargiya müşahidə edilə bilər.

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...

Villitis of unknown etiology (VUE) is noninfectious chronic villitis thought to be associated with fetal growth restriction and stillbirth. COVID-19 and the pandemic SARS-CoV-2 infection can cause an increased risk in pregnant women for potential maternal and fetal complications from an immunological mechanism. We report a 39-week-gestational-age infant delivered to a 37-year-old mother diagnosed with SARS-CoV-2 infection at 37 weeks gestation. The placental examination showed the morphological features of VUE. We showed immunohistochemically that macrophages and CD4-positive T cells predominated in the villous tissue, although elevated numbers of CD8-positive cells were also present. We hypothesize that VUE may represent a maternal anti-viral immune response, in this case to SARS-CoV-2.

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.

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.

Due to immaturity of immune function and the possibility of mother-fetal vertical and aerosol transmissions, neonates are particularly susceptible to the new coronavirus (SARS-CoV-2). Perinatal-neonatal departments should cooperate closely and take integrated approaches, and neonatal intensive care units (NICU) should prepare emergency plans for the coronavirus disease 2019 (COVID-19) as far as possible, so as to ensure the optimal management and treatment of potential victims. During the epidemic of COVID-19, the emergency response plan for the NICU should be based on the actual situation, including diagnosis, isolation, and treatment, as well as available equipment and staffing, and take into account the psychosocial needs of the families and neonatal care staff. In this context of the COVID-19 pandemic, the Turkish Neonatal Society has proposed a protocol with the evidence available at the time of preparation to handle neonates with SARS-CoV-2 infections and outbreaks in NICUs. We hope that this proposal can provide valuable information so medical workers do not have to enter the battlefield alone. At this moment, sharing resources, experiences and lessons, regardless of who you are, is our only chance to win.

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.

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.

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.

The aim of this study was to investigate the possible neuroprotective and ameliorating effects of leptin treatment in hypoxic-ischemic injury induced neuronal cell death.Experimental groups in the study were: sham-operated group, leptin treated hypoxia-ischemia group, and vehicle treated hypoxia-ischemia group. In hypoxia-ischemia group, left common carotid artery was ligated permanently on the seventh postnatal day. Two hours after the procedure, hypoxia (92% nitrogen and 8% oxygen) was applied for 2.5 h. Leptin treatment was injected (intraperitoneally; i.p.) as a single dose immediately after the hypoxia period. Neuronal cell death, neuronal density, and leptin levels were evaluated in both hemispheres 72 h after the hypoxic-ischemic insult.Compared with the hypoxic-ischemia group, the mean leptin levels were higher in the brains of the sham group for both hemispheres. The leptin treatment significantly diminished the number of 'apoptotic cells' in the hippocampal CA1, CA2, CA3, and gyrus dentatus regions in both hemispheres. Leptin treatment significantly preserved the number of neurons in both hemispheres, when compared with the vehicle treated group.We conclude that leptin treatment improves neuronal density and decreases apoptosis in the newborn rat with hypoxic-ischemic brain injury.

Aim: To elucidate the genetic factors causing hyperbilirubinaemia in prolonged jaundice of the newborns, we investigated whether the HO-1 gene promoter polymorphism is a cause in unexplained pathological or prolonged jaundice. Methods: Three groups were defined: healthy newborns with no clinical jaundice, newborns hospitalized for jaundice without any identifiable pathological cause and newborns with prolonged jaundice associated with breast milk. Genomic DNA was extracted from the white blood cells and the promoter region of the HO-1 gene was amplified using PCR and their allelic repeats were determined. Results: We did not detect any significant difference in the allele frequencies between the healthy newborns and the newborns whose serum total bilirubin levels were >12.9 mg/dL. However, the patients with short (

Aminophylline is widely used in the management of premature apnea. The methylxanthines aminophylline, theophylline and caffeine are nonspecific inhibitors of adenosine receptors. There are no proven effects of methylxanthines on acute brain injury and long-term cognitive functions. This study is aimed at investigating the effects of methylxanthines on brain injury and cognitive functions. Newborn rats were allocated to form four groups, which contained at least 21 pups: two groups were exposed to room air and two groups were exposed to intermittent hypoxia. Intraperitoneal aminophylline was administered to treatment groups during postnatal day 1 through postnatal day 7. All rats were sacrificed on postnatal day 8 via intraperitoneal pentobarbital and the effects of the administered drug on brain injury and adenosine receptor expression were determined. Cognitive functions of rats were evaluated via water maze test. Histopathological evaluation demonstrated that aminophylline significantly diminished the number of 'apopto tic cells' in the hippocampal CA1, CA2, CA3 and gyrus dentatus regions in the brain. Aminophylline treatment immediately after hypoxic insult significantly improved long-term neurobehavioral achievements. In conclusion, aminophylline administration immediately after neonatal hypoxic insult provides benefit over a prolonged period in the developing rat brain. Copyright (C) 2010 S. Karger AG, Basel

Perinatal hypoxia-ischemia remains the single most important cause of brain injury in the newborn, leading to death or lifelong sequelae. White matter injuries in newborn infants have long-term effects on physical, visual, motor, sensory, cognitive and social development in human infants. There is no known cure for neonatal hypoxic ischemic encephalopathy (NHIE). Activated protein C has potent anticoagulant activity due to its ability to inactivate factor Va and VIIIa. APC is the first effective biological therapy approved for the treatment of severe sepsis. Although APC is well defined as a physiological anticoagulant, emerging data suggest that it also has cytoprotective, anti-inflammatory and antiapoptotic properties. APC has been shown to provide neuroprotection in ischemic brain and spinal cord injury. Here, we propose that APC, which modulates many of these processes, may represent a promising therapeutic agent for NHIE. Seven days old Wistar Albino rat pups have been used in the study (n = 42). Experimental groups in the study were: sham-operated group, APC treated group, and vehicle treated group. in hypoxia-ischemia groups, the left common carotid artery was ligated permanently on the seventh postnatal day. Two hours after the procedure, hypoxia (92% nitrogen and 8% oxygen) was applied for 2.5 h. APC were injected (intraperitoneally; i.p.) as a single dose immediately after the hypoxia period. Brain nitrite levels, neuronal cell death, and apoptosis were evaluated in both hemispheres 72 h after the hypoxic-ischemic insult. Histopathological evaluation demonstrated that APC significantly diminished the number of "apoptotic cells" in the hippocampal CA1, CA2, CA3 and gyrus dentatus regions in both hemispheres. APC treatment significantly reduced 11 apoptotic cell death" in both hemispheres, when compared with vehicle treated group. APC significantly preserved the number of neurons CA1, CA3 regions of the hippocampus, when compared with vehicle treated group. our results showed that hypoxic-ischemic injury caused a significant increase in NO production. The APC-treated animals were reduced brain nitrite levels in carotid ligated hemispheres. To our knowledge, this is the first study that demonstrates a protective effect of the APC against hypoxia-ischemia in the developing brain. (C) 2008 Published by Elsevier B.V.

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.

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.

Background: Thermal management of the very low-birthweight (VLBW) infant is a cornerstone of neonatology because thermal stress is an important determinant of survival. This prospective study was designed to determine the effects of polyethylene occlusive skin wrapping on heat loss in VLBW infants admitted to the neonatal intensive care unit (NICU) promptly after birth. Methods: Thirty consecutively inborn infants weighing

Background: The purpose of the present paper was to prospectively determine the rate of β-lactam antibiotic resistance in commensal fecal flora of newborns and the risk factors leading to this colonization. Methods: One hundred and eighteen newborns in the neonatal intensive care unit (NICU) group (n = 38), the neonatal ward group (n = 36), and the control group (n = 44) were enrolled. Three or four stool samples were obtained from each infant, 15 days apart. Bacterial growth in Eozin Methylene Blue (EMB) agar + 10 µg ampicillin/mL was considered to be ampicillin-resistant bacteria, and antibiotic susceptibility and extended spectrum β-lactamases (ESBL) production was investigated in those bacteria. Results: Colonization with ampicillin-resistant commensal fecal flora microorganisms was determined in 75.2% of 367 stool samples. Klebsiella spp. and Escherichia coli were identified in 59% and 41% of the samples, respectively. The lowest rate of ampicillin-resistant bacterial colonization was determined in the NICU group. Microorganisms producing ESBL were identified in 33.7% of 367 stool samples. Fifty-one and 73 of ampicillin-resistant E. coli and Klebsiella spp. isolates were determined to produce ESBL, respectively. There was no difference with respect to colonization with ESBL-producing microorganisms between the three groups. When risk factors related to colonization with ESBL-producing microorganisms in stool samples were evaluated through the whole study period, very low birthweight, vaginal delivery, infant antibiotic usage, maternal antibiotic usage, male sex and premature rupture of membranes were determined as risk factors, while feeding with nasogastric tube was identified as a protective factor. When the risk factors related to colonization with ESBL-producing bacteria in stool samples after discharge from the hospital were evaluated, failure to feed breast milk was determined as the only risk factor. Conclusions: To decrease mortality and morbidity due to infection caused by resistant microorganisms colonized in the intestine flora of the infant, protection of normal non-pathogenic bacterial colonization is important. This can be provided by feeding neonates with breast milk, application of infection control measures efficiently, and limitation of antibiotic usage only to strict clinical indications.

Objectives: To evaluate the effects of long-term patient triggered ventilation (PTV) using assist/ control or synchronized intermittent mandatory ventilation (SIMV) in very-low-birth-weight infants with respiratory distress. Methods: Ninety-seven very-low-birth-weight infants who had undergone synchronized ventilation for respiratory distress or insufficiency were assessed from January 1995 to December 2000. Death, oxygen support, pneumothorax development while ventilated, intracranial hemorrhage, necrotizing enterocolitis, periventricular leukomalacia, retinopathy of prematurity and duration of ventilation were noted as the mean outcome measures. Results: The mean birth weight was 1139 ± 268 g (range 450-1500 g) and the mean gestational age was 29.0 ± 2.8 weeks (range 23-36 weeks). Eighty-four per cent of 97 infants survived. Antenatal steroids were administered to only 20% of mothers. Surfactant was administered to all of the 67% of infants with respiratory distress syndrome. The mean duration of ventilator support was 4.7 ± 7.3 days (1-43 days) for survivors and 8.9 ± 11 days (1-45 days) for infants who died. No respiratory paralysis was necessary in any case during ventilation and pneumothorax was diagnosed in only eight infants. Severe intracranial hemorrhage (grade ≥ III) and periventricular leukomalacia developed in 15% and 12% of infants, respectively. Necrotizing enterocolitis (Bell's classification stage ≥ 2) and retinopathy of prematurity were noted in two infants. Four infants had evidence of chronic lung disease. The rate of survival without major morbidity was 83.5%. Conclusion: Patient-triggered ventilation, initially PTV with Asist/Control and subsequently with SIMV in very-low-birth-weight infants with respiratory distress is feasible, but optimization of trigger and ventilator performance with respect to respiratory diagnosis is essential.

To illustrate neonatal outcomes, including morbidity, birth weight and gestational age-specific mortality, and care practices for very-low-birth-weight infants admitted to our tertiary neonatal intensive care unit in Turkey and compare these with the corresponding data from recent reports from developed countries.Perinatal data were collected prospectively from January 1996 to December 2000. Perinatal events and the neonatal course to 120 days of life, discharge, or death were evaluated.Of 173 infants, 82% survived until discharge to home or to 120 days of life. Survival was 13% for infants of 501-750 g at birth, 74% for those of 751-1000 g, 92% for those of 1001-1250 g and 87% for those of 1251-1500 g. Mortality rates were greater for male than for female infants (25% vs. 12%). The mean birth weight was 1218 (450-1500) g and the mean gestational age was 29.8 (23-36) weeks. The birth weight and gestational age distributions showed that the majority of infants (48%) weighed 1251-1500 g and were between 28 and 31 weeks' gestation (57%). Antenatal steroids were administered to only 19% of mothers. The overall Cesarean section rate was 77%. Respiratory distress syndrome was diagnosed in 36% and surfactant was administered to 98% of these infants. The rate of ventilator support was 54% for a mean duration of 9 days. Air leak syndromes were diagnosed in only nine infants (5%). Severe intracranial hemorrhage (gradeII) and periventricular leukomalacia developed in 9% of infants. Four infants had evidence of chronic lung disease. Retinopathy of prematurity (stageII) was noted in only one infant, and proven necrotizing enterocolitis (Bell's classification stage2) was not observed. The rate of survival without major morbidity was 91%. The mean hospital stay was 40 days for survivors and 19 days for infants who died.Despite marked differences in socioeconomic conditions and tertiary care facilities, the mortality (except in the smallest babies) and morbidity rates were comparable with those of recent studies from developed countries.

Background A newborn with cholestatic hepatic disease and hemophagocytic lymphohistiocytosis due to rhesus hemolytic disease (RHD) is reported. Observation A 34 weeks' gestation baby with RHD, who had received multiple intrauterine transfusions (IUT), developed cholestatic hepatic disease and secondary hemophagocytic lymphohistiocytosis (HLH). Her serum ferritin level increased to 5,527 ng/mL, and liver biopsy showed severe iron overload. Treatment with intravenous desferrioxamine resulted in a marked decrease in serum ferritin levels and normalization of liver function Conclusion We suggest that patients who have undergone IUT be evaluated for hyperferritinemia. If hyperferritinemia is noted, chelation therapy should be considered. As another rare finding, HLH can complicate the course of RHD.

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.

Aim To evaluate the significance of the cord blood ischemia-modified albumin (IMA) level as a diagnostic marker for perinatal asphyxia and to determine the associations of IMA levels with the complexity of pregnancy and abnormal Doppler findings, regardless of perinatal asphyxia. Methods This prospective study included 169 newborns, sixteen of whom had perinatal asphyxia and 33 who were from complicated pregnancies. Doppler measurements were obtained from the uterine, umbilical and middle cerebral arteries, and the cerebro/placental ratio (C/P). IMA was measured by means of commercially available ELISA kits and was expressed as picomoles per milliliter. Results Ischemia-modified albumin levels were significantly higher in neonates of complicated pregnancies as compared to uncomplicated pregnancies (P

We present a preterm female infant with an unusual vascular nevus on the lumbosacral and gluteal regions. Our clinical diagnosis was probable twin nevus, with a blanched nevus adjacent to a telangiectatic nevus, later complicated by ulceration. Ultrasonography and magnetic resonance imaging of the lumbosacral region revealed that her conus medullaris level was at L4 and the spinal cord was tethered by an intraspinal lipoma, without evidence of a hemangioma. We could not find any literature reporting the association of twin nevus with spinal dysraphism.