This review aims to give an updated overview of the worldwide situation of off-label and unlicensed drug use in the paediatric field, also taking into account the safety of this kind of treatment. A Medline and Embase search was performed between 1990 and 2006 and a total of 52 studies were identified and included in the systematic review. From the authors' analysis of the literature, the extent of paediatric unlicensed/off label use is higher in neonatal and paediatric intensive care units and oncology wards, compared with primary care. Moreover, among the nine studies reporting the contribution of an off-label/unlicensed drug use to the occurrence of adverse events, the percentage of unlicensed and/or off-label prescriptions involved in an adverse drug reaction ranged between 23 and 60%. To ensure that children are not exposed to unnecessary risks, controlled clinical trials are required. In addition, future research should be directed towards the identification of individual drugs that cause serious adverse drug reactions and lack product information.

These recommendations are endorsed by the Italian Society of Pediatric Nephrology. They can also be a tool of comparison with other existing guidelines in issues in which much controversy still exists.

Wildlife has often presented and suggested the effects of endocrine disrupting chemicals (EDCs). Animal studies have given us an important opportunity to understand the mechanisms of action of many chemicals on the endocrine system and on neurodevelopment and behaviour, and to evaluate the effects of doses, time and duration of exposure. Although results are sometimes conflicting because of confounding factors, epidemiological studies in humans suggest effects of EDCs on prenatal growth, thyroid function, glucose metabolism and obesity, puberty, fertility, and on carcinogenesis mainly through epigenetic mechanisms. This manuscript reviews the reports of a multidisciplinary national meeting on this topic.

Since few data are available about factors affecting renal maturation especially in the lower gestational ages (G.A.), the aim of this work was to study postnatal renal function in a representative population sample of preterm newborns (G.A.

The new coronavirus disease outbreak in 2019 (COVID-19) represents a dramatic challenge for healthcare systems worldwide. As to viral tropism, lungs are not the only COVID-19 target but also the heart may be involved in a not negligible percentage of the infected patients. Myocarditis-related cardiac dysfunction and potentially life-threatening arrhythmias are the main aftermaths. A few studies showed that myocardial injury in adult patients is often linked with a fatal outcome. Conversely, scientific evidence in children is sparse, although several reports were published with the description of a cardiac involvement in COVID-19 paediatric patients. In these young subjects, a background of surgically treated congenital heart disease seems to be a predisposing factor. Conclusion: This systematic review is aimed at summarizing all COVID-19 cases with a cardiac involvement published in paediatric age and trying to explain the underlying mechanisms responsible for COVID-19-related myocardial damage. What is Known: • Coronaviruses proved to be able to jump from animals to humans. • The outbreak of COVID-19 started from China (Dec 2019) and became pandemic. What is New: • Even in childhood, COVID-19 is not without the risk of cardiac involvement. • Myocarditis, heart failure, and arrhythmias are among the possible manifestations.

Starting from the Developmental Origins of Health and Disease (DOHaD) hypotheses proposed by David Barker, namely fetal programming, in the past years, there is a growing evidence of the major role played by epigenetic factors during the intrauterine life and the perinatal period. Furthermore, it has been assessed that these factors can affect the health status in infancy and even in adulthood. In this review, we focus our attention on the fetal programming of the brain, analyzing the most recent literature concerning the epigenetic factors that can influence the development of neuropsychiatric disorders such as bipolar disorders, major depressive disorders, and schizophrenia. The perinatal epigenetic factors have been divided in two main groups: maternal factors and fetal factors. The maternal factors include diet, smoking, alcoholism, hypertension, malnutrition, trace elements, stress, diabetes, substance abuse, and exposure to environmental toxicants, while the fetal factors include hypoxia/asphyxia, placental insufficiency, prematurity, low birth weight, drugs administered to the mother or to the baby, and all factors causing intrauterine growth restriction. A better comprehension of the possible mechanisms underlying the pathogenesis of these diseases may help researchers and clinicians develop new diagnostic tools and treatments to offer these patients a tailored medical treatment strategy to improve their quality of life. Birth Defects Research (Part C) 108:207-223, 2016. © 2016 Wiley Periodicals, Inc.

Childhood aggression and its resulting consequences inflict a huge burden on affected children, their relatives, teachers, peers and society as a whole. Aggression during childhood rarely occurs in isolation and is correlated with other symptoms of childhood psychopathology. In this paper, we aim to describe and improve the understanding of the co-occurrence of aggression with other forms of childhood psychopathology. We focus on the co-occurrence of aggression and other childhood behavioural and emotional problems, including other externalising problems, attention problems and anxiety–depression. The data were brought together within the EU-ACTION (Aggression in Children: unravelling gene-environment interplay to inform Treatment and InterventiON strategies) project. We analysed the co-occurrence of aggression and other childhood behavioural and emotional problems as a function of the child’s age (ages 3 through 16 years), gender, the person rating the behaviour (father, mother or self) and assessment instrument. The data came from six large population-based European cohort studies from the Netherlands (2x), the UK, Finland and Sweden (2x). Multiple assessment instruments, including the Child Behaviour Checklist (CBCL), the Strengths and Difficulties Questionnaire (SDQ) and Multidimensional Peer Nomination Inventory (MPNI), were used. There was a good representation of boys and girls in each age category, with data for 30,523 3- to 4-year-olds (49.5% boys), 20,958 5- to 6-year-olds (49.6% boys), 18,291 7- to 8-year-olds (49.0% boys), 27,218 9- to 10-year-olds (49.4% boys), 18,543 12- to 13-year-olds (48.9% boys) and 10,088 15- to 16-year-olds (46.6% boys). We replicated the well-established gender differences in average aggression scores at most ages for parental ratings. The gender differences decreased with age and were not present for self-reports. Aggression co-occurred with the majority of other behavioural and social problems, from both externalising and internalising domains. At each age, the co-occurrence was particularly prevalent for aggression and oppositional and ADHD-related problems, with correlations of around 0.5 in general. Aggression also showed substantial associations with anxiety–depression and other internalizing symptoms (correlations around 0.4). Co-occurrence for self-reported problems was somewhat higher than for parental reports, but we found neither rater differences, nor differences across assessment instruments in co-occurrence patterns. There were large similarities in co-occurrence patterns across the different European countries. Finally, co-occurrence was generally stable across age and sex, and if any change was observed, it indicated stronger correlations when children grew older. We present an online tool to visualise these associations as a function of rater, gender, instrument and cohort. In addition, we present a description of the full EU-ACTION projects, its first results and the future perspectives.

To date, we have little knowledge on the overall metabolic status of neonates with intrauterine growth retardation (IUGR). In the last few years, the analysis of metabolomics has assumed an important clinical role in identifying "disorders" in the metabolic profile of patients. The aim of this work has been to analyze the urine metabolic profiles of neonates with IUGR and compare them with controls to define the metabolic patterns associated with this pathology. To our knowledge, this is the first study of metabolomics performed on neonates with IUGR. Recruited for the study were 26 neonates with IUGR diagnosed in the neonatal period and with weight at birth below the 10th percentile and 30 neonates of proper gestational weight at birth (controls). In the first 24 hours (prior to feeding) (T1) and about 4 days after birth (T2), a urine sample was taken non-invasively from each neonate. The samples were then frozen at -80°C up to the time of the analysis by proton nuclear magnetic resonance spectroscopy (1H-NMR). The data contained in the NMR spectra obtained from the single samples were statistically analyzed using the Principal Components Analysis and the Partial Least Squares-Discriminate Analysis. By means of a multivariate analysis of the NMR spectra obtained, it was possible to highlight the differences between the two groups (IUGRs and controls) owing to the presence of different metabolic patterns. The discriminants in the urine metabolic profiles derived essentially from significant differences in certain metabolites such as: myo-inositol, sarcosine, creatine and creatinine. The metabolomic analysis showed different urine metabolic profiles between neonates with IUGR and controls and made it possible to identify the molecules responsible for such differences.