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There is increased interest in the interactions between vascular disorders and Alzheimer’s disease (AD). While initially these interactions were explained by the fact that these are both very common disorders, particularly later in life, recently, the possibility that these deficiencies might actually coexist is increasingly being questioned. This review attempts to present modern aspects and current reports regarding the interactions between AD, the renin-angiotensin system (RAS) and hypertension, while also describing the relevance of antihypertensive drug use acting via the RAS in the treatment and prevention of AD, as well as the importance of oxidative stress, the alteration of the balance between antioxidants and pro-oxidants, in the interaction between AD and the RAS.

Background/Objectives : Prolonged prelabour rupture of membranes (PROMs), and the resulting inflammatory response, can contribute to the occurrence of adverse neonatal outcomes, especially for early-preterm neonates. This prospective study aimed to measure neonates' inflammatory markers in the first 72 h of life based on ROM duration. The second aim was to examine the relationship between PROMs, serum inflammatory markers, and composite adverse neonatal outcomes after controlling for gestational age (GA). Methods : Data from 1026 patients were analyzed considering the following groups: group 1 (ROM < 18 h, n = 447 patients) and group 2 (ROM > 18 h, n = 579 patients). These groups were further segregated depending on the GA at the moment of membranes' rupture into subgroup 1 (<33 weeks of gestation and 6 days, n = 168 patients) and subgroup 2 (at least 34 completed weeks of gestation, n = 858 patients). Multiple logistic regressions and interaction analyses adjusted for GA considering five composite adverse neonatal outcomes and predictors were employed. Results : PROMs and high c-reactive protein (CRP) values significantly increased the risk of composite outcome 1 occurrence by 14% (95%CI: 1.03-1.57, p < 0.001). PROMs and high CRP values increased the risk of composite outcome 5 by 14% (95%CI: 1.07-1.78, p < 0.001), PROM and leukocytosis by 11% (95%CI: 1.02-1.59, p = 0.001), and PROMs and high PCT values by 21% (95%CI: 1.04-2.10, p < 0.001). Conclusions : The combination of PROMs and high CRP values significantly increased the risk of all evaluated adverse composite outcomes in early-preterm neonates and should point to careful monitoring of these patients.

(1) Background: Neonatal early-onset sepsis (EOS) is associated with important mortality and morbidity. The aims of this study were to evaluate the association between serum and hematological biomarkers with early onset neonatal sepsis in a cohort of patients with prolonged rupture of membranes (PROM) and to calculate their diagnostic accuracy. (2) Methods: A retrospective cohort study was conducted on 1355 newborns with PROM admitted between January 2017 and March 2020, who were divided into two groups: group A, with PROM ≥ 18 h, and group B, with ROM < 18 h. Both groups were further split into subgroups: proven sepsis, presumed sepsis, and no sepsis. Descriptive statistics, analysis of variance (ANOVA) and a Random Effects Generalized Least Squares (GLS) regression were used to evaluate the data. (3) Results: The statistically significant predictors of neonatal sepsis were the high white blood cell count from the first ( p = 0.005) and third day ( p = 0.028), and high C-reactive protein (CRP) values from the first day ( p = 0.004). Procalcitonin (area under the curve-AUC = 0.78) and CRP (AUC = 0.76) measured on the first day had the best predictive performance for early-onset neonatal sepsis. (4) Conclusions: Our results outline the feasibility of using procalcitonin and CRP measured on the first day taken individually in order to increase the detection rate of early-onset neonatal sepsis, in the absence of positive blood culture.

Takotsubo Syndrome (TS) is an acute, reversible cardiac dysfunction, with complex, not entirely understood pathophysiology and heterogeneous clinical picture. Imaging methods each have a crucial role in the diagnosis, in-hospital management, short term and long term follow up. Coronary angiography needs to be performed, especially in the setting of a suspected acute coronary syndrome, in order to rule out coronary artery disease. Echocardiography plays a central role both in the acute and the chronic phase. It is the first imaging investigation performed in patients with TS, valuable to diagnose systolic dysfunction, the wall motion pattern and early complications. Cardiac magnetic resonance tissue characterization provides an essential role in the differential diagnosis of TS with other non-ischemic causes of systolic dysfunction. This review focuses on the imaging methods and the important part they play in the complex management of the disease., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 The Author(s). Published by IMR Press.)

Secondary diabetes mellitus is frequently ignored in specialized literature. In this narrative review, the main endocrinopathies accompanied by increased glycemic values are identified, as well as the mechanisms by which the excess or deficiency of certain hormones impact beta cell function or insulin resistance. The main endocrinopathies (acromegaly, Cushing's syndrome, Basedow-Graves' disease, pheochromocytoma, somatostatinoma and glucagonoma) and their characteristics are described along with the impact of hormone changes on blood sugar, body mass index and other parameters associated with diabetes. The overall information regarding the complex molecular mechanisms that cause the risk of secondary diabetes and metabolic syndrome is of crucial importance in order to prevent the development of the disease and its complications and particularly to reduce the cardiovascular risk of these patients. The purpose of this study is to highlight the particular features of endocrine pathologies accompanied by an increased risk of developing diabetes, in the context of personalized therapeutic decision making. The epidemiological, physiopathological, clinical and therapeutic approaches are presented along with the importance of screening for diabetes in endocrine diseases.

(1) Background: Retinopathy of prematurity (ROP) can cause severe visual impairment or even blindness. We aimed to assess the hematological risk factors that are associated with different stages of ROP in a cohort of preterm newborns, and to compare the clinical characteristics and therapeutic interventions between groups. (2) Methods: This retrospective study included 149 preterm newborns from a tertiary maternity hospital in Romania between January 2018 and December 2018, who were segregated into: Group 1 (with ROP, n = 59 patients), and Group 2 (without ROP, n = 90 patients). The patients that were affected by ROP were subsequently divided into the following subgroups: Subgroup 1 (Stage 1, n = 21), Subgroup 2 (Stage 2, n = 35), and Subgroup 3 (Stage 3, n = 25). The associations were analyzed using multivariate logistic regression and sensitivity analysis. (3) Results: Platelet mass indexes (PMI) that were determined in the first, seventh, and tenth days of life were significantly associated with Stage 1 ROP. PMI determined in the first day of life was also significantly associated with Stage 2 ROP. The sensitivity and specificity of these parameters were modest, ranging from 44 to 57%, and 59 to 63%. (4) Conclusions: PMI has a modest ability to predict the development of ROP.

(1) Background: Isotretinoin (ISO) is a systemic retinoid known for its teratogenic effects on embryos and fetuses. The aim of this study was to compare the pregnancy outcomes of women who were exposed to isotretinoin with those of women without such exposure from a teratogenic point of view. (2) Methods: A total of 1459 female patients from three clinical hospitals in Poland and Romania, segregated into two groups depending on their ISO exposure, were evaluated between January and December 2019. Medical records were screened to identify the pregnancy outcomes and congenital malformation rates. (3) Results: The congenital malformation rate for the exposed group was 1.2% (four cases), and no specific signs of Accutane embryopathy were identified. Women from the unexposed group were more likely to deliver preterm and through cesarean deliveries and had a higher rate of newborn congenital malformations as compared to women from the exposed group. (4) Conclusions: Even though we could not find a significant association between ISO exposure and teratogenic effects in newborns, effective contraceptive measures are key to preventing unfavorable pregnancy outcomes.

Objective: We compared birth injuries for spontaneous vaginal (VD) and caesarean section (CS) deliveries in preterm and term pregnancies., Methods: A retrospective cohort study was conducted in a single tertiary center, between January 1st, 2007, and December 31st, 2017. The study included 62330 singleton pregnancies delivered after 24 0/7 weeks gestation. Multivariable analyses compared trauma at birth, birth hypoxia and birth asphyxia in term and preterm deliveries, stratified by mode of birth, VD versus CS. Main outcome measure was trauma at birth including intracranial laceration and haemorrhage, injuries to scalp, injuries to central and peripheral nervous system, fractures to skeleton, facial and eye injury., Results: The incidence of preterm deliveries was 10.9%. Delivery of preterm babies by CS increased from 37.0% in 2007 to 60.0% in 2017. The overall incidence of all birth trauma was 16.2%. When stratified by mode of delivery, birth trauma was recorded in 23.4% of spontaneous vaginal deliveries and 7.5% of CS deliveries (aOR 3.3, 95%CI 3.1-3.5). When considered all types of birth trauma, incidence of trauma at birth was higher after 28 weeks gestation in VD compared to CS (28-31 weeks, aOR 1.7, 95% CI 1.3-2.3; 32-36 weeks, aOR 4.2, 95% CI 3.6-4.9; >37 weeks, aOR 3.3, 95% CI 3.1-3.5). There was no difference in the incidence of birth trauma before 28 weeks gestation between VD and CS (aOR 0.8, 95% CI 0.5-1.2). Regarding overall life-threatening birth trauma or injuries at birth with severe consequences such as cerebral and intraventricular haemorrhage, cranial and brachial nerve injury, fractures of long bones and clavicle, eye and facial injury, there was no difference in vaginal preterm deliveries compared to CS deliveries (p > 0.05 for all)., Conclusion: CS is not protective of injury at birth. When all types of birth trauma are considered, these are more common in spontaneous VD, thus favoring CS as preferred method of delivery to avoid trauma at birth. However, when stratified by severity of birth trauma, preterm babies delivered vaginally are not at higher risk of major birth trauma than those delivered by CS., Competing Interests: The authors have declared that no competing interests exist.

(1) Background: Neonatal cerebral sinovenous thrombosis (CSVT) is a rare disorder, associated with long-term neurological sequelae. The aim of this study was to retrospectively evaluate the most commonly encountered perinatal risk factors for this disease in a cohort of newborns from Romania. (2) Methods: The medical records of neonatal CSVT patients treated between January 2017 and December 2021 were descriptively assessed. (3) Results: The study included nine neonates, five males (55.56%) and four females (44.44%), who were born at term. The most commonly presented clinical manifestations were feeding difficulties, lethargy, respiratory distress, loss of consciousness, and seizures. Maternal-inherited thrombophilia, male sex, complicated delivery, perinatal asphyxia, and mechanical ventilation were frequently identified as potential risk factors for developing CSVT. The lesions were more frequently localized in the superior sagittal sinus (n = 7; 77.78%), followed by the transverse (n = 4; 44.44%), sigmoid (n = 2; 22.22%), and cavernous (n = 1; 11.11%) sinuses. Low-molecular-weight heparin was administered to all patients, and two of them died from thrombotic complications. (4) Conclusions: Recognition of potential risk factors and a prompt diagnosis of neonatal CSVT could lead to better patient management and to a reduction of severe complications.

Background-Children with genetic disorders have multiple anatomical and physiological conditions that predispose them to obstructive sleep apnea syndrome (OSAS). They should have priority access to polysomnography (PSG) before establishing their therapeutic protocol. We analyzed the prevalence and the severity of OSAS in a particular group of children with genetic disorders and strengthened their need for a multidisciplinary diagnosis and adapted management. Methods-The retrospective analysis included children with genetic impairments and sleep disturbances that were referred for polysomnography. We collected respiratory parameters from sleep studies: apnea-hypopnea index (AHI), SatO 2 nadir, end-tidal CO 2 , and transcutaneous CO 2 . Subsequent management included non-invasive ventilation (NIV) or otorhinolaryngological (ENT) surgery of the upper airway. Results-We identified 108 patients with neuromuscular disorders or multiple congenital anomalies. OSAS was present in 87 patients (80.5%), 3 of whom received CPAP, 32 needed another form of NIV during sleep, and 15 patients were referred for ENT surgery. The post-therapeutic follow-up PSG parameters confirmed the success of the treatment. Conclusions-The upper airway obstruction diagnostics and management for children with complex genetic diseases need a multidisciplinary approach. Early detection and treatment of sleep-disordered breathing in children with genetic disorders is a priority for improving their quality of life.

Background and objectives: The connections between the imidazoline system and multiple other neurotransmitter systems in the brain (adrenergic, dopaminergic, serotoninergic, glutamatergic, opioid) indicate the complexity of the mechanisms underlying motor activity and behavior. The aim of the present research was to investigate the effects of the combination of ephedrine (EPD) and imidazoline antagonists idazoxan (IDZ) and efaroxan (EFR) on the endurance performance in the treadmill test in rats. Materials and Methods: We used Wistar rats distributed as follows: Group 1 (Control) receiving distilled water 0.3 mL/100 g body weight; Group 2 (EPD) receiving 20 mg/kg ephedrine; Group 3 (EPD + IDZ) receiving 20 mg/kg ephedrine + 3 mg/kg idazoxan; Group 4 (EPD + EFR) receiving 20 mg/kg ephedrine + 1 mg/kg efaroxan. An additional group (C) of animals receiving 0.3 mL/100 g body weight distilled water (but not subjected) to effort was used. Endurance capacity was evaluated using a treadmill running PanLAB assay. The evaluation of the substances' influence on oxidative stress was performed by spectrophotometric determination of superoxide dismutase (SOD) and glutathione peroxidase (GPX) activity. Results: Treatment with EPD-IDZ and EPD-EFR were correlated with a longer distance traveled on the belt and with a decrease in the necessary electric shocks to motivate the animal to continue running in the forced locomotion test. Additionally, an increase in the activity of antioxidant enzymes was found. Conclusions: Idazoxan and efaroxan potentiated the physical effort-related effects of ephedrine with regard to endurance capacity and antioxidant activity in rats.

Neonatal early-onset sepsis (EOS) is defined as an invasive infection that occurs in the first 72 h of life. The incidence of EOS varies from 0.5-2% live births in developed countries, up to 9.8% live births in low resource settings, generating a high mortality rate, especially in extremely low birth weight neonates. Clinical signs are nonspecific, leading to a late diagnosis and high mortality. Currently, there are several markers used for sepsis evaluation, such as hematological indices, acute phase reactants, cytokines, which by themselves do not show acceptable sensitivity and specificity for the diagnosis of EOS in neonates. Newer and more selective markers have surfaced recently, such as presepsin and endocan, but they are currently only in the experimental research stages. This comprehensive review article is based on the role of biomarkers currently in use or in the research phase from a basic, translational, and clinical viewpoint that helps us to improve the quality of neonatal early-onset sepsis diagnosis and management.

Chronic kidney disease and Alzheimer's disease are chronic conditions highly prevalent in elderly communities and societies, and a diagnosis of them is devastating and life changing. Demanding therapies and changes, such as non-compliance, cognitive impairment, and non-cognitive anomalies, may lead to supplementary symptoms and subsequent worsening of well-being and quality of life, impacting the socio-economic status of both patient and family. In recent decades, additional hypotheses have attempted to clarify the connection between these two diseases, multifactorial in their nature, but even so, the mechanisms behind this link are still elusive. In this paper, we sought to highlight the current understanding of the mechanisms for cognitive decline in patients with these concurrent pathologies and provide insight into the relationship between markers related to these disease entities and whether the potential biomarkers for renal function may be used for the diagnosis of Alzheimer's disease. Exploring detailed knowledge of etiologies, heterogeneity of risk factors, and neuropathological processes associated with these conditions opens opportunities for the development of new therapies and biomarkers to delay or slow their progression and validation of whether the setting of chronic kidney disease could be a potential determinant for cognitive damage in Alzheimer's disease.

Background and objectives: Self-medication is a global phenomenon in both developed and emerging countries. At present, data regarding the practice, patterns, and factors associated with self-medication in Romanian patient groups of various ages and health are relatively scarce. A pilot study that uses a questionnaire was conducted to observe the attitudes as well as the behaviors of a group of Romanian parents related to self-medication, specifically their beliefs and perceived risks of the administration of medicine to their children without medical advice, frequency of self-medications, symptoms, and types of medications most commonly used without medical advice. Materials and Methods: The questionnaire was sent via e-mail or WhatsApp link on a mobile phone using the existing data at the general practitioner's office together with the protection of data form and the informed consent form; some participants completed the questionnaire when they came for a regular visit at the general practitioner's office. Of 246 applied questionnaires, we had a rate of responses of 98%. Results: We found a high percentage (70%) of parents who self-medicate their children. The data reveals a significant relation between parents' beliefs on self-medication and their tendency to administrate drugs to their children without medical advice. A significant relation was also found between the likelihood of parental self-medication for their children and the number of illnesses experienced by their children over the six-month period prior to the survey. Even when parents have a correct understanding of self-medication risks, these are not aligned with actual behavior; therefore, parents continue to administer drugs to their children without medical advice. Conclusions: Our study helps to describe the patterns of parents' decisions about self-medicating their children and to identify parents who are more predisposed to administering self-medication to their children.

Alzheimer's disease is a neurodegenerative disorder for which there is a continuous search of drugs able to reduce or stop the cognitive decline. Beta-amyloid peptides are composed of 40 and 42 amino acids and are considered a major cause of neuronal toxicity. They are prone to aggregation, yielding oligomers and fibrils through the inter-molecular binding between the amino acid sequences (17-42) of multiple amyloid-beta molecules. Additionally, amyloid deposition causes cerebral amyloid angiopathy. The present study aims to identify, in the existing literature, natural plant derived products possessing inhibitory properties against aggregation. The studies searched proved the anti-aggregating effects by the thioflavin T assay and through behavioral, biochemical, and histological analysis carried out upon administration of natural chemical compounds to transgenic mouse models of Alzheimer's disease. According to our present study results, fifteen secondary metabolites from plants were identified which presented both evidence coming from the thioflavin T assay and transgenic mouse models developing Alzheimer's disease and six additional metabolites were mentioned due to their inhibitory effects against fibrillogenesis. Among them, epigallocatechin-3-gallate, luteolin, myricetin, and silibinin were proven to lower the aggregation to less than 40%.

Diabetes and Alzheimer's disease are two highly prevalent diseases among the aging population and have become major public health concerns in the 21st century, with a significant risk to each other. Both of these diseases are increasingly recognized to be multifactorial conditions. The terms "diabetes type 3" or "brain diabetes" have been proposed in recent years to provide a complete view of the potential common pathogenic mechanisms between these diseases. While insulin resistance or deficiency remains the salient hallmarks of diabetes, cognitive decline and non-cognitive abnormalities such as impairments in visuospatial function, attention, cognitive flexibility, and psychomotor speed are also present. Furthermore, amyloid aggregation and deposition may also be drivers for diabetes pathology. Here, we offer a brief appraisal of social impact and economic burden of these chronic diseases and provide insight into amyloidogenesis through considering recent advances of amyloid-β aggregates on diabetes pathology and islet amyloid polypeptide on Alzheimer's disease. Exploring the detailed knowledge of molecular interaction between these two amyloidogenic proteins opens new opportunities for therapies and biomarker development ., Competing Interests: The authors declare no conflict of interest.

Introduction: Endocan is a specific endothelial mediator involved in the inflammatory response. Its role in the diagnosis of sepsis has been studied in adult patients and late onset neonatal sepsis. The clinical signs of early onset sepsis (EOS) are nonspecific and routinely used biomarkers, such as C-reactive protein and procalcitonin, have low sensitivity, specificity and positive predictive value. Endocan could be useful as a biomarker for diagnosis of EOS, but at present normal range values for this molecule have not been reported. The aim of this study is to establish the normal values range for serum endocan in term and preterm newborns without risk factors for EOS and to characterize the variation pattern of its levels at different postnatal moments., Methodology: Mean endocan serum concentration (ESC) was measured in term and preterm newborns without clinical suspicion of EOS at different moments from birth., Results: ESC (ng/mL) in term newborns was 1.74+/-0.13 on day 1 and 2.02+/-0.41 on day 3 respectively, (p=0.09). In preterm newborns ESC (ng/mL) was 2.02+/-0.11 and 1.97+/-0.18, (p=0.8) for day 1 and 3 respectively. ESC was not significantly influenced by sex, mode of delivery, evidence of fetal distress or presence of minor birth trauma., Conclusions: ESC (ng/mL) between the first and third day of life in either term or preterm infants don't appear to be significantly influenced by factors that are associated with elevation of inflammatory markers, thus using this biomarker for the diagnosis of EOS might reduce the false positive results., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2019 Luminita Paduraru, Gabriela Ildiko Zonda, Radu Zonda, Andrei Tudor Cernomaz, Bogdan Dragos Grigoriu.)

Introduction: Neonatal early onset sepsis assessment is based on the history of pregnancy and delivery and nonspecific clinical signs. None of the biomarkers currently in use for clinical practice has adequate prognostic value, so it is not possible to clearly distinguish neonates with culture-proven sepsis from those with only risk factors or clinical suspicion. Endocan is an endothelial mediator involved in the inflammatory response that is present in low concentrations in the serum of healthy subjects, and in much higher concentrations in patients with SIRS and septic shock. The purpose of this study is to evaluate the utility of serum endocan serum levels as a biomarker for the diagnosis of neonatal early onset sepsis (EOS)., Methodology: Serum endocan concentration was measured in newborns with clinical suspicion of EOS admitted to the Neonatal Intensive Care Unit on day 1, 3 and 7., Results: Serum endocan levels were significantly increased in septic compared to non-septic neonates in the early stages of sepsis (2.43 ± 0.95 vs. 1.77 ± 0.57, p = 0.004), continued to rise up to 72 hours from onset and then decreased by the seventh day under treatment., Conclusions: These results suggest a potential role for endocan as an early marker for diagnosis and follow-up in neonatal EOS. Studies on a larger number of cases are needed in order to establish the practical utility of this molecule as a diagnostic tool for clinical practice., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2019 Gabriela Ildiko Zonda, Radu Zonda, Andrei Tudor Cernomaz, Luminita Paduraru, Andreea Luciana Avasiloaiei, Bogdan Dragos Grigoriu.)

Nevus comedonicus is considered a genodermatosis characterized by the presence of multiple groups of dilated pilosebaceous orifices filled with black keratin plugs, with sharply unilateral distribution mostly on the face, neck, trunk, upper arms. Lesions can appear at any age, frequently before the age of 10 years, but they are usually present at birth. We present a 2.7-year-old girl with a very severe form of nevus comedonicus. She exhibited lesions located initially at the left side of the body with a linear characteristic, following Blascko lines T1/T2, T5, T7, S1 /S2, but progressively developed lesions on the right side of the scalp and left gluteal area.

Interstitial cells of Cajal (ICCs) are located in various smooth muscle organs and act as pacemaker cells, or ensure neuromodulation or mechanosensory roles. The study aims to investigate functional states of human ICCs in morphogenesis, focusing on the anoctamin 1 phenotype. The investigation was performed in five late stage human embryos with lengths varying between 23 and 29 mm. Immunohistochemistry on paraffin embedded specimens was performed for a series of antibodies: a-smooth muscle actin (a-SMA), desmin, CD31, CD34, CD117/c-kit, DOG1, and nestin. Longitudinal and circular muscle layers were a-SMA1/desmin1/nestin1. An immature microvascular layer located in the inner submucosa was CD341/CD311/a-SMA1/ nestin1; endothelial tip cells were supporting active processes of sprouting angiogenesis. A CD341/CD31- mesenchymal network was found in the circular muscle layer. CD117/c-kit1 multipolar ICCs with dichotomizing processes were found mostly in the myenteric plexus layer; processes were configuring a network within the circular muscle layer where intramuscular ICCs were scarcely found. A strong DOG11 reaction was found for the ICCs of the myenteric plexus layer apposed on the outer surface of the circular muscle layer, and for the intramuscular ICCs. The evidence of a sublayer of DOG11 myenteric ICCs is suggestive for a subpopulation of ICCs being qualified for pacemaking at this early developmental stage., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: The aim of this study was to compare two neuroprotective strategies to supportive care in the treatment of perinatal asphyxia., Methods: A total of 67 term newborns with perinatal asphyxia were included and randomized into three groups: one group received supportive treatment; another group received a single dose of 40 mg/kg phenobarbital; and the third received three daily doses of 1000 IU/kg erythropoietin. The following parameters were analyzed: gestational age, birthweight, Apgar scores, cord blood pH, total serum antioxidant status (TAS), superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA). The newborns were included in the follow-up program and examined up to 18 months of age., Results: TAS was higher in the erythropoietin group than in the other groups. SOD and GPx were lower for infants treated with phenobarbital or erythropoietin compared to control infants. MDA was lower in the erythropoietin group compared to the other groups, although the difference was not statistically significant (P > 0.05). The mortality rate was lower in the phenobarbital and erythropoietin groups (both 4.6%) than in the control group (17.4%). Long-term neurologic follow up showed a high incidence of sequelae in the control group compared to the phenobarbital and erythropoietin groups. Follow-up results were better in the phenobarbital group than in the erythropoietin group for motor and cognitive function at 3 and 6 months and worse for expressive language. At 18 months, however, the differences between these two groups were not significant., Conclusion: High-dose phenobarbital or erythropoietin along with supportive treatment has a positive influence on the outcome of newborns with perinatal asphyxia. Phenobarbital has the advantage of low cost and simplicity., (© 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.)