Current Pediatric Reviews - Volume 3, Issue 1, 2007

Premature birth is associated with a number of adverse sequaelae; these include bronchopulmonary dysplasia, necrotizing enterocolitis, intracerebral haemorrhage and retinopathy of prematurity. It has been suggested that these conditions are the outcome of “oxygen radical disease” [1] and occur as a result of oxidative injury. Premature infants often require high inspired supplemental oxygen concentrations because of lung disease and severe sepsis. These conditions are associated with reduced cardiac output and hypotension, which may lead to hypoxemia of the tissues. This can result in the generation of oxygen derived free radicals (reactive oxygen species (ROS)). To defend against the actions of ROS, there are antioxidants such as ascorbic acid (vitamin C) and tocopherol (Vitamin E) and enzymatic defenses such as super oxide dismutase (SOD), glutathionine peroxidase and catalase. Unfortunately, the premature infant has poor antioxidant defense mechanisms. In this issue of the journal Tsopmo and Friel [2] report data from a literature review to highlight that human milk has antioxidant properties. In particular, they note that human milk contains vitamins C and E and enzymes including superoxide dismutase, catalase and glutathione peroxidase. Human milk is often frozen and stored for deferred use for very prematurely born and sick infants. Freezing decreases the antioxidant activity of milk in a time dependent fashion [3], but the antioxidant activity of human milk, despite storage, is still higher than that of infant formulae. This may at least partially explain why prematurely born infants fed with breast milk rather than cow's milk based infant formulae have a lower incidence of nectrotising enterocolitis [4] and retinopathy of prematurity [5]. REFERENCES [1] Saugstadt OD. Oxygen toxicity in the neonatal period. Acta Pediatr Scand 1990; 79: 881-92. [2] Tsopmo A, Friel JK. Human milk has anti-oxidant properties to protect premature infants. Curr Ped Rev 2007; 3: 47-54. [3] Hanna N, Ahmed K, Anwar M, Petrova A, Hiatt M, Hegyi T. Effect of storage on breast milk antioxidant activity. Arch Dis Child Fetal Neonatal Ed 2004; 89: F518-20. [4] Lucas A, Cole TJ. Breast milk and necrotizing enterocolitis. Lancet 1990; 336: 1519-23. [5] Cunningham AS. Breast feeding, antioxidants and the retinopathy of prematurity. Am J Obstet Gynecol 1987; 156: 1040-1.

The receptor for advanced glycation endproducts (RAGE) has been shown to play an important role in aging, neurodegeneration, diabetes, and inflammation. RAGE is a transmembrane receptor of the immunoglobuline superfamily, which recognizes a variety of ligands such as AGEs (advanced glycation endproducts), members of the S100/calgranulin family of proinflammatory mediators, β-sheet-fibrills, HMGB1 (amphoterin) and the β2-integrin Mac-1. RAGE/ligand interactions induce oxidative stress and lead to an up-regulation of pro-inflammatory pathways involving the proinflammatory transcription factor NF-κB, increased expression of cytokines, chemokines, and adhesion molecules. These effects markedly propagate cellular dysfunction and cause perturbation in a diverse group of diseases, such as agerelated neurodegenerative disorders, atherosclerosis, diabetic vascular complications, tumors, and chronic inflammatory disease. In addition, RAGE may also interfere with differentiation processes, which are required during organ development. In this article, we have reviewed recent advances on RAGE and RAGE/ligand function in cell adhesion and inflammation based on findings from cell cultures, animal models, and human diseases. The potential for targeting the RAGE/ligand pathway as therapeutic strategy will be discussed.

Infection with hepatitis A virus (HAV) is common in children. Among children < 5 years of age, <10% present with jaundice and manifest HAV infection with diarrhea, nausea, vomiting, malaise or no visible signs or symptoms. Prior to introduction of hepatitis A vaccine in the United States, the reported incidence of symptomatic disease was highest among children 5 to 14 years of age (15.6/100,000), however, seroprevalence data indicated that children <5 years of age had the highest infection incidence (637.4/100,000). The significance of these finding is that young children with asymptomatic infection act as silent reservoirs for HAV transmission within the community. Hepatitis A immunization provides long-term immunity against HAV infection and early childhood immunization has been shown to halt HAV transmission in communities with previously high incidence of disease. Incorporation of hepatitis A vaccine into the early childhood immunization schedule was impeded by the finding that passively acquired maternal antibody significantly inhibited immunogenicity of vaccine administered during infancy. However, recent studies have shown that little passively acquired antibody remains early in the second year of life and does not interfere with vaccine immunogenicity. Early childhood hepatitis A vaccination has significantly lowered disease incidence in a number of populations, worldwide. Among vaccinated and unvaccinated children, there has been a > 85% reduction in disease incidence and a 69-90% reduction in disease incidence among unvaccinated adults in the same populations. The effectiveness and costeffectiveness of childhood hepatitis A vaccination combined with no increase in adverse events among more than 2.3 million vaccinated children has led to recent recommendations that hepatitis A vaccine be incorporated into the early childhood immunization schedule in the United States.

The fetal gastrointestinal tract is sterile until birth when microbes colonize the gastrointestinal tract, and a dense, complex microbiota develops. This enormous cell mass performs a variety of activities that affect both the intestinal and systemic physiology. The microbiota provides nutritional, metabolic, immunological, and protective functions. The neonatal gastrointestinal tract is an organ at risk. Increasing awareness that the human flora is a major factor in both health and disease has led to different strategies to manipulate the flora. Manipulation with prebiotics and probiotics has shown promising results although a better understanding of the gut bacterial colonization process is required before attempts to change the flora should be made. In this review, we summarize the data regarding developmental microbial ecology in the neonatal gastrointestinal tract, and the modulation of such microbiota. The discussion focuses on the control and manipulation of bacterial colonization in the neonatal gut for the prevention and treatment of bacterial intestinal disease in both in human infants and on animal models. Since the best available methodologies should be utilized in studies of nutritional sciences, a recapitulation of the latest techniques for the study of the gastrointestinal flora is presented. Future progress is likely to arise from the use of genomic techniques to track of dietinduced changes in microbiota.

Urinary tract infection, one of the commonest bacterial diseases in children, carries a substantial risk of serious complications. Amongst them, renal scarring and recurrent infections seem to be the most important. In this review, we analyze the pathogenesis of urinary tract infection in order to identify those children who run the highest risk of unfavorable outcome. During infection, multiple bacterial and host factors interact with each other. Bacteria possess specific characteristics involved in the process of adhesion, invasion, survival and host damage during infection. Host factors also substantially participate in the pathogenesis of the disease. According to current knowledge, the specific host response appears to be the main factor predisposing for complications. However, prompt and adequate treatment of acute urinary tract infection remains the most important measure to prevent scarring. Dysfunctional holding and elimination of urine, on the other hand, mainly seem to influence the development of recurrent infection. Despite intensive research for many years, urinary tract infections are still a challenge for patients and health care professionals.

Human milk (HM) is recognized as the optimal form of nutrition in the newborn period, providing nutrients and a variety of components (minerals, vitamins, enzymes, hormones, growth factors, and immunoglobulins) that are very important for growth and healthy development. In the case of premature (PM) infants, functional and in certain cases, structural development of most organ systems is completed in the weeks following birth. PM infants do not get enough oxygen and may require supplemental oxygen as high as 95%. This high level of inspired oxygen necessary to maintain arterial oxygen tension exposes these infants to more reactive oxygen species (ROS) compared with full term infants. ROS may lead to diseases associated with prematurity, including necrotizing enterocolitis, retinopathy of prematurity, intraventricular-periventricular hemorrhage, and bronchopulmonary dysplasia. There is then a need to reduce oxidative stress or boost antioxidant defenses in these vulnerable infants. Data suggest that HM has unique antioxidant properties that will assist the premature infant in coping with the increased oxidative stress. HM antioxidant components include the enzymes superoxide dismutase for dismutation of superoxide anion, catalase for degradation of hydrogen peroxide (H2O2), glutathione peroxidase for destruction of H2O2 and organic peroxides. Human milk contains other molecules including cysteine, vitamins C and E, which are scavengers of oxygen radicals.

Mitochondrial fatty acid β-oxidation disorders are relatively common causes of acute metabolic crises and sudden death in infants. Most of these disorders can be treated effectively, provided, fasting is avoided and there is an early start of a high-carbohydrate low-fat diet therapy. Two disorders, long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and complete mitochondrial trifunctional protein (MTP) deficiencies, have pathogenetically interesting and therapeutically challenging manifestations, which are atypical of β-oxidation defects. In addition to the classical manifestations of disorders affecting β-oxidation of long-chain fatty acids (hypoketotic hypoglycaemia, hepatopathy, cardiomyopathy and rhabdomyolysis), patients with LCHAD and MTP defects have pigmentary retinopathy, which causes visual handicap, progressive peripheral neuropathy and hypoparathyreosis. Furthermore, female carriers may have devastating pre-eclampsia-related complications and in particular acute fatty liver during pregnancy. Pathogenesis research of the important characteristic features of LCHAD and MTP deficiencies would not only improve opportunities for new therapeutic strategies but could increase our understanding of tissue metabolism affected by these disorders.

Identifying atypical trajectories that distinguish children with differing developmental disorders from each other and from typically developing children is a potentially powerful tool for early ascertainment and treatment of syndrome specific proficiencies and deficiencies. The past decade has seen unparalleled advances in the fields of molecular genetics, pediatrics, developmental cognitive neuroscience and brain imaging. Collaboratively, these advances have facilitated our understanding of how genes can impact upon early development, through the identification of specific patterns of cognitive and behavior processing and the deficits in these domains that are typical to a specific developmental disorder. These advances have also made early diagnoses possible for many developmental disorders, including those for which genetic etiology has yet to be determined, such as is the case for most individuals with autism, or disorders such as fragile X syndrome that result from the silencing of a single gene. This early identification necessitates thorough investigation of the impact of a condition across the lifespan beginning in early childhood when interventions are most likely to have significant benefit. This is especially relevant for disorders that at first glance appear to share overlapping behavioral and clinical symptomology. In the case of autism and fragile X syndrome, commonalties in social and communication profiles are now well documented in early childhood. However, to what degree symptom overlap implies common developmental pathways or etiologies remains unclear. The focus of this review will be to critically evaluate whether so called 'commonalities' in phenotypic outcomes actually reflect very different developmental pathways that diverge over developmental time and across syndromes. More detailed knowledge of these profiles will facilitate early timing of tailored interventions that will promote optimal development resulting in significant educational, clinical, and adaptive benefits across a child's lifespan.

Back Pain [BP] represents one of the most common occupational disorders among human beings, with almost all people experiencing it at some stage during their life. Despite the well-known relationships between workplace factors and BP among adults, BP also affects younger people, such as school children and university students. Although some evidence suggests an increasing prevalence of BP throughout later childhood, it is difficult to ascertain whether this reflects a true increase in prevalence, or just greater recognition of the problem by researchers and research subjects. Nevertheless, various studies have begun to highlight a variety of BP risk factors in young people, such as classroom posture, backpacks, computer usage and psychosocial factors. As today's school children and university students may be a generation increasingly burdened by BP, it is essential that clinicians in the paediatric field keep abreast of contemporary issues and risks, so that they may more effectively deal with this growing menace.

Introduction. There is growing body of evidence to suggest that pharmacotherapy may be a rational form of intervention for some patients with pervasive developmental disorders (PDDs). The purpose of this article is to describe what is known about medication treatment for these patients. Methods. Published papers regarding the pharmacotherapy of PDDs were collected and reviewed. For each study, particular attention was paid to ascertaining patient characteristics, the medication doses employed, and medication tolerability. Results. There is evidence of varying methodological rigor to suggest that several medications may have a role in the treatment of patients with PDDs. However, to date, few randomized double-blind treatment studies have been published. In addition, there is very little known about the long-term safety of many of these agents in this patient population. Conclusions. Some patients with PDDs may benefit acutely from pharmacotherapy. Many marketed psychotropic agents that putatively hold promise for these patients have not been rigorously studied. More short-term and long-term research regarding the pharmacotherapy of patients with PDDs is needed.

Objective: Conduct a review of clinical trials to identify effective approaches for improving physician provision of alcohol education and counseling services among outpatient adolescents. Methods: Reviewed all peer-reviewed, published clinical trials identified through computerized searches evaluating alcohol education and counseling services to outpatient adolescents by physicians. Results: Three trials were identified examining changes in physician provision of alcohol education and counseling services. One of the trials resulted in increased adolescent self-reported refusal skills, while another trial resulted in reduction of adolescent self-reported alcohol use and binge drinking. Seven trials were identified that compared physician with non-physician provision of alcohol education and counseling services. Four of the trials showed some reduction in adolescent self-reported alcohol use. Conclusion: Trials indicate that further reduction in adolescent alcohol use is possible with non-physicians as interventionists and perhaps physicians as interventionists, if physicians are supported by patient counseling guides and resources. Opportunities for personalized, interactive adolescent education with goal setting appears key to intervention success. The physician role that is tested in most trials is confined to a single brief encounter with little attention to: development of physician skills, systems-level resources, the parental role, or the impact of incorporating prevention into an ongoing adolescent-physician relationship.