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Background and Objective: We present an overview of the 2024 updates for the European Association of Urology (EAU)/European Society for Paediatric Urology (ESPU) guidelines on paediatric urology to offer evidence-based standards for perioperative management, minimally invasive surgery (MIS), hydrocele, congenital lower urinary tract obstruction (CLUTO), trauma/emergencies, and fertility preservation., Methods: A broad literature search was performed for each condition. Recommendations were developed and rated as strong or weak on the basis of the quality of the evidence, the benefit/harm ratio, and potential patient preferences., Key Findings and Limitations: Recommendations for perioperative management include points related to fasting, premedication, antibiotic prophylaxis, pain control, and thromboprophylaxis in patients requiring general anaesthesia. MIS use is increasing in paediatric urology, with no major differences observed among different MIS approaches. For hydrocele, observation is the initial approach recommended. For persistent cases, treatment varies according to the type of hydrocele. CLUTO cases should be managed in tertiary centres with multidisciplinary expertise in prenatal and postnatal management. Neonatal valve ablation remains the mainstay of treatment, but associated bladder dysfunction requires continuous treatment. Among urological traumas and emergencies, renal trauma is still an important cause of morbidity and mortality. Conservative management has become the standard approach in haemodynamically stable children. Ischaemic priapism is a medical emergency and requires stepwise management. Initial management of nonischaemic priapism is conservative. Fertility preservation in prepubertal children and adolescents has become an increasingly relevant issue owing to the ever-increasing number of cancer survivors receiving gonadotoxic therapies. A major limitation is the scarcity of relevant literature., Conclusions and Clinical Implications: This summary of the 2024 EAU/ESPU guidelines provides updated guidance for evidence-based management of some paediatric urological conditions., Patient Summary: We provide a summary of the updated European Association of Urology/European Society for Paediatric Urology guidelines on paediatric urology. There are recommendations on steps to take before and immediately after surgery, management of hydrocele, congenital lower urinary tract obstruction, and urological trauma/emergencies, as well as preservation of fertility. Recommendations are based on a comprehensive review of recent studies., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction:  The aim of this study was to assess the adherence to the European Association of Urology (EAU)/European Society for Pediatric Urology (ESPU) 2016 guidelines in the management of undescended testes (UDT)., Materials and Methods:  An online questionnaire was sent in 2023 to members of the European Paediatric Surgeons' Association (EUPSA)., Results:  Among 157 members, 46 and 44% perform orchidopexy before 12 and 18 months, respectively. In total, 92% recommend conservative management of retractile testes and 58% offer close follow-up. In case of nonpalpable testes, 78% favor laparoscopy and 18% ultrasonography. If a peeping testicle is identified at laparoscopy, 76% perform a single-stage orchidopexy. In case of a high testicle, a staged procedure is preferred (84%). Management of blind-ending spermatic vessel is heterogenous with a majority ending the operation, followed by exploration of the inguinal canal and removal of the testicular nubbin with optional fixation of the contralateral testis. Only a minority recommends hormonal therapy to improve fertility potential in bilateral UDT. A majority (59%) discuss testis removal in UDT in postpubertal boys. In addition, 77% declare following the EAU/ESPU guidelines. Unawareness of guidelines was the most common reason cited for nonadherence. International guidelines were found to have the greatest influence on clinical practice; however, personal experience and institutional practice seem to play an important role., Conclusion:  Most recommendations of the EAU/ESPU guidelines are being followed by EUPSA members; however, personal and institutional practice impact decision making. Hormonal therapy in bilateral UDT, management of vanishing testes, and UDT in postpubertal boys could be improved., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: In post-mortem (PM) fetal and neonatal imaging, relevant clinical information is crucial for accurate interpretation and diagnosis; however, it is usually incomplete., Objective: To propose a standardized template for PM fetal and neonatal imaging referrals to enhance communication between referring clinicians and reporting radiologists., Materials and Methods: A modified Delphi approach was conducted amongst members of the European Society of Paediatric Radiology (ESPR) PM Task Force and other recommended PM imaging specialists worldwide to determine consensus on necessary information. These were based on three pre-existing referral templates already in use across a variety of centers. The study ran for 4 months (December 2023-April 2024)., Results: Nineteen specialists from 17 centers worldwide formed our expert panel. The final agreed referral template information includes the patient's identification details (mother and fetus when available), fetal/neonatal information (gestational age, sex, type of demise (including type of termination of pregnancy (i.e., surgical or medical)), date and time of fetal demise (+ delivery) or neonatal death, singleton/multiple pregnancy, clinical information (obstetrical history, prenatal imaging findings, amniocentesis findings, physical external examination findings), provisional clinical diagnosis, and ordering physician's information., Conclusion: A comprehensive referral template has been created, representing expert consensus on the minimum data required for the conduct of quality PM fetal and neonatal imaging, with the goal of facilitating accuracy of image interpretation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: This exploratory study evaluates rating scale usage by experts from the European Reference Network for Rare Neurological Diseases (ERN-RND) for paediatric MD, considering factors like diagnosis, intellectual disability, age, and transition to adult care. The aim is to propose a preliminary framework for consistent application., Methods: A multicentre survey among 25 ERN-RND experts from 10 European countries examined rating scale usage in paediatric MD, categorizing MD into acute, non-progressive, and neurodegenerative types. Factors influencing scale choice and the transition to adult care practices were analysed. A comprehensive literature search was conducted to identify the earliest age of application of these scales in paediatric patients., Results: The study identifies various rating scales and establishes their usage frequencies for different MDs. Experts highlighted the need for standardized scales and proposed preliminary evaluation strategies based on clinical contexts. Challenges in applying scales to young, non-cooperative patients were acknowledged., Interpretation: The study recommends developing standardized rating scales for paediatric MDs to improve evaluations and data collection. It suggests potential scales for specific clinical scenarios to better evaluate disease progression. Comprehensive, patient-centred care remains crucial during the transition to adult care, despite the identified challenges. This exploratory approach aims to enhance patient outcomes and care., Competing Interests: Declaration of competing interest We hereby affirm that all authors involved in the preparation of this manuscript declare no conflicts of interest. This includes financial, personal, or professional relationships that could potentially influence the interpretation of the work presented herein., (Copyright © 2024 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Over the last decades, magnetic resonance imaging (MRI) has emerged as a valuable adjunct to prenatal ultrasound for evaluating fetal malformations. Several radiological societies advocate for standardised and structured reporting practices to enhance the uniformity of imaging language. Compared to narrative formats, standardised and structured reports offer enhanced content quality, minimise reader variability, have the potential to save reporting time, and streamline the communication between specialists by employing a shared lexicon. Structured reporting holds promise for mitigating medico-legal liability, while also facilitating rigorous scientific data analyses and the development of standardised databases. While structured reporting templates for fetal MRI are already in use in some centres, specific recommendations and/or guidelines from international societies are scarce in the literature. The purpose of this paper is to propose a standardised and structured reporting template for fetal MRI to assist radiologists, particularly those with less experience, in delivering systematic reports. Additionally, the paper aims to offer an overview of the anatomical structures that necessitate reporting and the prevalent normative values for fetal biometrics found in current literature., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Organization of healthcare strongly differs between European countries and results in country-specific requirements in postgraduate medical training. Within the European Union (EU), the European Board of Anaesthesiology has set recommendations of training for the Specialty of Anaesthesiology including standards for Postgraduate Medical Specialist training including a description for providing service in pediatric anesthesia. However, these standards are advisory and not mandatory. Here we aimed to review the current state and associated challenges of pediatric anesthesia training in Europe. We report an important country-specific variability both in training and regulations of practice of pediatric anesthesia in the EU and in the United Kingdom. The requirements for training in pediatric anesthesia varies between nothing specified (Belgium) or providing anesthesia with direct supervision to a minimum of 50 cases below 5 years of age (Germany) to 3-6 month clinical practice in a specialized pediatric hospital (France). Likewise, the regulations for providing anesthesia to children varies from no regulations at all (Belgium) to age specific requirements and centralization of all children below 4 years of age to specified centers (United Kingdom). Officially recognized pediatric anesthesia fellowship programs are not available in most countries of Europe. It remains unclear if and how country-specific differences in pediatric anesthesia training are associated with clinical outcomes in pediatric perioperative care. There is converging interest and support for the establishment of a European pediatric anesthesia curriculum., (© 2024 The Authors. Pediatric Anesthesia published by John Wiley & Sons Ltd.)

This document has been developed to provide a guide for basic and advanced reporting in paediatric echocardiography. Furthermore, it aims to help clinicians in the interpretation of echocardiographic measurements and functional data for estimating the severity of disease in different paediatric age groups. The following topics will be reviewed and discussed in the present document: (i) the general principle in constructing a paediatric echocardiographic report, (ii) the basic elements to be included, and (iii) the potential and limitation of currently employed tools used for disease severity quantification during paediatric reporting. A guide for the interpretation of Z-scores will be provided. Use and interpretation of parameters employed for quantification of ventricular systolic function will be discussed. Difficulties in the adoption of adult parameters for the study of diastolic function and valve defects at different ages and pressure and loading conditions will be outlined, with pitfalls for the assessment listed. A guide for careful use of prediction scores for complex congenital heart disease will be provided. Examples of basic and advanced (disease-specific) formats for reporting in paediatric echocardiography will be provided. This document should serve as a comprehensive guide to (i) structure a comprehensive paediatric echocardiographic report; (ii) identify the basic morphological details, measures, and functional parameters to be included during echocardiographic reporting; and (iii) correctly interpret measurements and functional data for estimating disease severity., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Intravenous maintenance fluid therapy (IV-MFT) is probably the most prescribed drug in paediatric hospital care. Recently paediatric societies have produced evidence-based practice guidelines that recommend the use of balanced isotonic fluid when prescribing IV-MFT in both acute and critical paediatric care. Unfortunately, the applicability of these guidelines could be called into question when a ready-to-use glucose-containing balanced isotonic fluid is not available. The main objective of this study was to describe the availability of glucose-containing balanced isotonic fluids in European and Middle Eastern paediatric acute and critical care settings. This work is an ancillary study of the survey dedicated to IV-MFT practices in the paediatric acute and critical care settings in Europe and Middle East, a cross-sectional electronic 27-item survey, emailed in April-May 2021 to paediatric critical care physicians across 34 European and Middle East countries. The survey was developed by an expert multi-professional panel within the European Society of Peadiatric and Neonatal Intensive Care (ESPNIC). Balanced isotonic fluid with glucose 5% was available for only 32/153 (21%) responders. Balanced isotonic fluid with glucose 5% was consistently available in the UK (90%) but not available in France, Greece, The Netherlands and Turkey.    Conclusion: Ready-to-use isotonic balanced IV solutions containing glucose in sufficient amount exist but are inconsistently available throughout Europe. National and European Medication Safety Incentives should guarantee the availability of the most appropriate and safest IV-MFT solution for all children. What is Known: • Intravenous maintenance fluid therapy (IV-MFT) is probably the most prescribed drug in paediatric hospital care. • Balanced isotonic fluid is recommended when prescribing IV-MFT in both acute and critical paediatric care. What is New: • Balanced isotonic fluid with glucose 5% is available for less than 25% of the prescribers in Europe and the Middle East. Availability of balanced isotonic fluid with glucose 5% varies from one country to another but can also be inconsistent within the same country. • Clinicians who have access to a ready-to-use balanced isotonic fluid with glucose 5% are more likely to consider its use than clinicians who do not have access to such an IV solution., (© 2024. The Author(s).)

One of the biggest challenges in pediatric drug development is defining a safe and effective dose in pediatric populations, which span across a wide age and development range from neonates to adolescents. Model-informed drug development approaches are particularly suited to address knowledge gaps including data leveraging to increase the success of pediatric studies. Considering the often limited number of patients available for study and logistic difficulties to collect the necessary data in pediatric populations, the application of pharmacometrics and modeling and simulation techniques can improve clinical trial efficiency, increase the probability of regulatory success, and optimize therapeutic individualization in support of dedicated trials. This review describes the state of pediatric model-informed drug development to define the right dose for children and provides suggestions for future development., (© 2021, The American College of Clinical Pharmacology.)

Getting the right dose regimen for children and adolescents is important but poses great scientific, practical, and ethical challenges. At the same time, the availability of data in adults is a huge advantage and needs to be used optimally when designing studies in children and analyzing pediatric data. Furthermore, the processes of maturation and growth are always key when selecting doses for children. All the above make study adaptations and model-informed approaches imperative for dose exposure-response characterization and dose selection in children. This article summarizes the experience gained in the European Medicines Agency on this topic and proposes some general guiding principles for defining objectives, study designs, and methodology tools for pediatric dose selection., (© 2021, The American College of Clinical Pharmacology.)

Background: Due to the growing risk of obesity and related diseases in the population of children, effective preventive measures are of great importance. Front-of-pack (FOP) nutrition labelling may contribute to health promotion by increasing consumer awareness on the nutritional qualities of packaged foods and purchasing decisions, and it may stimulate food providers to improve the composition of products., Summary: Appropriate labelling should enable customers to make healthy choices quickly and intuitively. Key Messages: The European Academy of Paediatrics and the European Childhood Obesity Group makes an appeal to European Union legislators to immediately introduce a mandatory, uniform, and interpretative FOP nutrition labelling system., (© 2021 S. Karger AG, Basel.)

Background: The following position statement from the Union of the European Phoniatricians, updated on 25th May 2020 (superseding the previous statement issued on 21st April 2020), contains a series of recommendations for phoniatricians and ENT surgeons who provide and/or run voice, swallowing, speech and language, or paediatric audiology services., Objectives: This material specifically aims to inform clinical practices in countries where clinics and operating theatres are reopening for elective work. It endeavours to present a current European view in relation to common procedures, many of which fall under the aegis of aerosol generating procedures., Conclusion: As evidence continues to build, some of the recommended practices will undoubtedly evolve, but it is hoped that the updated position statement will offer clinicians precepts on safe clinical practice.

Health-care professionals who prescribe medicines have the professional duty to choose medicines that are in the best interest of their individual patient, irrespective if that patient is an adult or a child. However, the availability of medicines with an appropriate label for pediatric use is lagging behind those for adults, and even available pediatric drugs are sometimes not suitable to administer to children. Consequently, health-care professionals often have no other option than to prescribe off-label medicines to children. An important reason for use of off-label medicines is to improve access to (innovative) treatments or to address medical needs and preferences of patients, especially when no other options are available. However, off-label use of medicines is in general not supported by the same level of evidence as medicines licensed for pediatric use. This may result in increased uncertainty on efficacy as well as the risk for toxicity and other side effects. In addition, liability may also be of concern, counterbalanced by professional guidelines.Conclusion: The purpose of this joint EAP/ESDPPP policy statement is to offer guidance for HCPs on when and how to prescribe off-label medicines to children and to provide recommendations for future European policy.

In 2012, we published guidelines summarizing and evaluating late 2011 evidence for diagnosis and therapy of urea cycle disorders (UCDs). With 1:35 000 estimated incidence, UCDs cause hyperammonemia of neonatal (~50%) or late onset that can lead to intellectual disability or death, even while effective therapies do exist. In the 7 years that have elapsed since the first guideline was published, abundant novel information has accumulated, experience on newborn screening for some UCDs has widened, a novel hyperammonemia-causing genetic disorder has been reported, glycerol phenylbutyrate has been introduced as a treatment, and novel promising therapeutic avenues (including gene therapy) have been opened. Several factors including the impact of the first edition of these guidelines (frequently read and quoted) may have increased awareness among health professionals and patient families. However, under-recognition and delayed diagnosis of UCDs still appear widespread. It was therefore necessary to revise the original guidelines to ensure an up-to-date frame of reference for professionals and patients as well as for awareness campaigns. This was accomplished by keeping the original spirit of providing a trans-European consensus based on robust evidence (scored with GRADE methodology), involving professionals on UCDs from nine countries in preparing this consensus. We believe this revised guideline, which has been reviewed by several societies that are involved in the management of UCDs, will have a positive impact on the outcomes of patients by establishing common standards, and spreading and harmonizing good practices. It may also promote the identification of knowledge voids to be filled by future research., (© 2019 SSIEM.)

Purpose: Conflicts of interest can impede both research and medical treatment. The European Reference Networks require their members to deal with financial and non-financial conflicts according to an explicit protocol. In a literature review, we identified relevant interests in paediatric surgery, and drafted such a policy., Methods: We conducted a Pubmed query and identified additional publications based on the content of the papers., Results: 58 titles were identified. According to their abstracts, 10 publications were studied in full text. A scientific taxonomy does not yet exist, but a variety of factors are mentioned. Non-financial conflicts of interest are addressed less accurately and less frequently than financial ones, especially regarding surgical treatment. Since the clinical effect of surgical volume was identified as being relevant, additional 29 respective publications were analysed. This volume-quality relationship causes conflicts of interest for the many surgeons treating a broad spectrum of rare conditions. We present a recommendation that may guide referral of patients requiring complex surgery to centres with a higher volume., Conclusions: Non-financial conflicts of interest need to be dealt with more accuracy, especially with regard to surgery in rare, complex congenital conditions. The European Reference Networks offer a framework to mitigate these conflicts.

Between 2015 and 2017, an estimated 200,000 to 400,000 children were seeking asylum each year in EU/EEA countries. As access to high-quality health care is important, we collected and compared current recommendations across Europe for a consensus recommendation on medical care for migrant (asylum-seeking and refugee) children. Existing recommendations were collected from published literature and identified through national representatives from paediatric societies of 31 EU/EEA countries through the European Academy of Paediatrics (EAP). Recommendations were systematically extracted and collected in a database. Those mentioned in at least one recommendation were evaluated for inclusion, and evidence on recommendations was specifically identified in literature searches focused on recent evidence from Europe. For eight EU/EEA countries, a national recommendation was identified. Growth and development, vision and hearing impairment, skin and dental problems, immunisations, anaemia, micronutrient deficiency, helminths, hepatitis B and C, human immunodeficiency virus, malaria, schistosomiasis, syphilis, tuberculosis, mental health disorder and sexual health were most frequently mentioned and therefore selected for inclusion in the recommendation.Conclusion: The current document includes general recommendations on ethical standards, use of interpreters and specific recommendations for prevention or early detection of communicable and non-communicable diseases. It may serve as a tool to ensure the fundamental right that migrant children in Europe receive a comprehensive, patient-centred health care.

The recent European Council Directive 2013/59/EURATOM requires the establishment of diagnostic reference levels (DRLs) to optimise radiation dose in diagnostic and interventional radiology procedures. At the time this directive was enacted, just a few European countries had already set paediatric DRLs and many of these were outdated. For this reason, the European Commission launched a project addressing European Guidelines on Diagnostic Reference Levels for Paediatric Imaging that was awarded to a consortium led by the European Society of Radiology with the collaboration of the European Society of Paediatric Radiology and other European stakeholders involved in the radiation protection of children. The main aims of this project were to establish European DRLs to be used by countries without their own national paediatric DRLs and to provide a consistent method to establish new DRLs in the future. These European guidelines have been very recently endorsed by the European Commission and published in issue N° 185 of the Radiation Protection series. The purpose of this article is to introduce these guidelines to the wide community of paediatric radiologists.

There is a need to measure and improve the quality of paediatric primary care in Europe where major differences in the delivery and outcomes of child health care exist. A collaborative panel of paediatric senior experts developed a Core Set of Indicators for Paediatric Primary Care in Europe by compiling 42 quality indicators in a modified consensus process following the RAND/UCLA appropriateness method. The aim of this study was to explore the feasibility of the quality indicator set in European paediatric primary care practices. Seventy-nine practices from eight countries participated in a detailed online interview. The practices rated the applicability, relevance, reliability and acceptance of the 42 quality indicator as well as the availability, technical feasibility and effort to retrieve the needed data from their medical records. Most quality indicators were considered applicable, available, reliable, acceptable and relevant for monitoring quality of care in paediatric primary care. Respondents rated feasibility and effort to retrieve the data lowest because of difficulties collecting the data from the medical records.Conclusion: European paediatric primary care practices generally agree with the proposed quality indicator set. They document most of the parameters. However, the collection of specific needed values from available routine patient-data is considered technically difficult and time-consuming. What is Known? • Paediatric primary care systems in Europe show striking differences in their performance. Pre-existing sets of quality indicators are predominantly limited to national populations, specific diseases and hospital care. • A Core Set of 42 quality indicators for paediatric primary care in Europe was developed by European paediatricians using a systematic literature review and a consensus process following a modified RAND/UCLA appropriateness method. What is New? • Paediatric primary care providers in Europe agree with the idea to use COSI-PPC-EU to monitor and improve the quality of care. The set was considered applicable, available, reliable, acceptable, and relevant for quality improvement. • The score for feasibility and effort to retrieve the data was low, because of technical reasons; the electronical or paper-based medical documentation in most cases does not allow convenient access to all necessary data.

Introduction: Primary FSGS is an important cause of ESRD in children. FSGS recurrence after kidney transplantation is associated with early graft loss. No guidelines for treatment of FSGS recurrence exist. We conducted a survey to gain insight into variation of treatment between centers., Methods: A survey was sent to all members of the ESPN on behalf of the "Renal Transplantation" and "Idiopathic Nephrotic Syndrome" working groups., Results: Fifty-nine nephrologists from 31 countries responded, reporting 807 FSGS patients, with 241 (30%) FSGS recurrences after transplantation. Recurrence varied from 0% to 100% between respondents. Native nephrectomy before or during transplantation was performed, respectively, always (37%), never (39%), or on clinical indication (17%). Half of the respondents started preventive treatment before transplantation, using PF (n = 10); R (n = 4); PF or IA, plus R (n = 9); cyclosporine (n = 2); or unknown (n = 4). Immunosuppressive therapy for patients without known mutations consisted of a combination of steroids, tacrolimus/cyclosporine, and MMF, with or without IL-2R-blockade in, respectively, 61% and 86% of the respondents. Sixty-three percent applied a similar regimen to patients with known mutations. FSGS recurrence was treated with PF or IA, plus R by 66% of respondents; 54% observed no response. Complete remission in >50% of patients was reported by 41% of the respondents., Discussion: FSGS recurrence after transplantation is common, but varies greatly between centers. We found great variability in preventive and therapeutic treatment regimens. Future research should focus on predisposing factors, including biopsy findings and genetic mutations, and standardized treatment., (© 2019 The Authors. Pediatric Transplantation Published by Wiley Periodicals, Inc.)

Objectives: The European Single Hub and Access point for paediatric Rheumatology in Europe initiative aimed to optimize care for children with rheumatic diseases. Kawasaki disease (KD) is the most common cause of acquired heart disease in children and an important cause of long-term cardiac disease into adulthood. Prompt diagnosis and treatment of KD is difficult due to the heterogeneity of the disease but is crucial for improving outcome. To date, there are no European internationally agreed, evidence-based guidelines concerning the diagnosis and treatment of KD in children. Accordingly, treatment regimens differ widely. The aim of this study is to provide consensus-based, European-wide evidence-informed recommendations for diagnosis and treatment of children with KD., Methods: Recommendations were developed using the EULAR's standard operating procedures. An extensive systematic literature search was performed, and evidence-based recommendations were extrapolated from the included papers. These were evaluated by a panel of international experts via online surveys and subsequently discussed in three consensus meetings, using nominal group technique. Recommendations were accepted when ⩾80% agreed., Results: In total, 17 recommendations for diagnosis and 14 for treatment of KD in children were accepted. Diagnostic recommendations included laboratory and imaging workup for complete as well as incomplete KD. Treatment recommendations included the importance of early treatment in both complete and incomplete KD, use of intravenous immunoglobulin, aspirin, corticosteroids for high-risk cases, and other treatment options for those with resistant disease., Conclusion: The Single Hub and Access point for paediatric Rheumatology in Europe initiative provides international evidence-based recommendations for diagnosing and treating KD in children, facilitating improvement and uniformity of care., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: The European initiative Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) aimed to optimize care for children with rheumatic diseases. Systemic vasculitides are very rare in children. Consequently, despite recent advances, paediatric-specific information is sparse. The lack of evidence-based recommendations is an important, unmet need. This study aimed to provide recommendations for diagnosing and treating children with rare forms of childhood systemic vasculitis., Methods: Recommendations were developed by a consensus process in accordance with the European League Against Rheumatism standard operating procedures. A systematic literature review informed the recommendations, which were devised and evaluated by a panel of experts via an online survey, and two consensus meetings using nominal group technique. Recommendations were accepted when ⩾ 80% of experts agreed., Results: Ninety-three relevant articles were found, and 78 recommendations were accepted in the two consensus meetings. General, cross-cutting recommendations and disease-specific statements regarding the diagnosis and treatment of childhood-onset PAN, granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and Takayasu arteritis are provided., Conclusion: These Single Hub and Access point for paediatric Rheumatology in Europe recommendations were formulated through an evidence-based consensus process to support uniform, high-quality standard of care for children with rare forms of paediatric systemic vasculitis., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Over the last several decades, many seminal longitudinal cohort studies have clearly shown that the antecedents to adult disease have their origins in childhood. Hypertension (HTN), which has become increasingly prevalent in childhood, represents one of the most important risk factors for cardiovascular diseases (CVD) such as heart disease and stroke. With the risk of adult HTN much greater when HTN is manifest in childhood, the future burden of CVD worldwide is therefore concerning. In an effort to slow the current trajectory, professional societies have called for more rigorous, evidence-based guideline development to aid primary care providers and subspecialists in improving recognition, diagnosis, evaluation, and treatment of pediatric HTN. In 2016 the European Society of Hypertension and in 2017 the American Academy of Pediatrics published updated guidelines for prevention and management of high blood pressure (BP) in children. While there are many similarities between the two guidelines, important differences exist. These differences, along with the identified knowledge gaps in each, will hopefully spur clinical researchers to action. This review highlights some of these similarities and differences, focusing on several of the more important facets regarding prevalence, prevention, diagnosis, management, and treatment of childhood HTN.

Fecal microbiota transplantation (FMT) is becoming part of the treatment algorithms against recurrent Clostridium difficile infection (rCDI) both in adult and pediatric gastroenterology practice. With our increasing recognition of the critical role the microbiome plays in human health and disease, FMT is also being considered as a potential therapy for other disorders, including inflammatory bowel disease (Crohn disease, ulcerative colitis), graft versus host disease, neuropsychiatric diseases, and metabolic syndrome. Controlled trials with FMT for rCDI have not been performed in children, and numerous clinical and regulatory considerations have to be considered when using this untraditional therapy. This report is intended to provide guidance for FMT in the treatment of rCDI in pediatric patients.

Treatment modalities for neonates born with congenital diaphragmatic hernia (CDH) have greatly improved in recent times with a concomitant increase in survival. In 2008, CDH EURO consortium, a collaboration of a large volume of CDH centers in Western Europe, was established with a goal to standardize management and facilitate multicenter research. However, limited knowledge on long-term outcomes restricts the identification of optimal care pathways for CDH survivors in adolescence and adulthood. This review aimed to evaluate the current practice of long-term follow-up within the CDH EURO consortium centers, and to review the literature on long-term outcomes published from 2000 onward. Apart from having disease-specific morbidities, children with CDH are at risk for impaired neurodevelopmental problems and failure of educational attainments which may affect participation in society and the quality of life in later years. Thus, there is every reason to offer them long-term multidisciplinary follow-up programs. We discuss a proposed collaborative project using standardized clinical assessment and management plan (SCAMP) methodology to obtain uniform and standardized follow-up of CDH patients at an international level.

Innovative research in childhood rheumatic diseases mandates international collaborations. However, researchers struggle with significant regulatory heterogeneity; an enabling European Union (EU)-wide framework is missing. The aims of the study were to systematically review the evidence for best practice and to establish recommendations for collaborative research. The Paediatric Rheumatology European Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) project enabled a scoping review and expert discussion, which then informed the systematic literature review. Published evidence was synthesised; recommendations were drafted. An iterative review process and consultations with Ethics Committees and European experts for ethical and legal aspects of paediatric research refined the recommendations. SHARE experts and patient representatives vetted the proposed recommendations at a consensus meeting using Nominal Group Technique. Agreement of 80% was mandatory for inclusion. The systematic literature review returned 1319 records. A total of 223 full-text publications plus 22 international normative documents were reviewed; 85 publications and 16 normative documents were included. A total of 21 recommendations were established including general principles (1-3), ethics (4-7), paediatric principles (8 and 9), consent to paediatric research (10-14), paediatric databank and biobank (15 and 16), sharing of data and samples (17-19), and commercialisation and third parties (20 and 21). The refined recommendations resulted in an agreement of >80% for all recommendations. The SHARE initiative established the first recommendations for Paediatric Rheumatology collaborative research across borders in Europe. These provide strong support for an urgently needed European framework and evidence-based guidance for its implementation. Such changes will promote research in children with rheumatic diseases., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement., (© 2016 The authors.)

Long-term follow-up of randomised trials and observational studies provide the best evidence presently available to assess long-term effects of nutrition, and such studies are an important component in determining optimal infant feeding practices. Attrition is, however, an almost inevitable occurrence with increasing age at follow-up. There is a common assumption that studies with <80% follow-up rates are invalid or flawed, and this criticism seems to be more frequently applied to follow-up studies involving randomised trials than observational studies. In this article, we explore the basis and evidence for this "80% rule" and discuss the need for greater consensus and clear guidelines for analysing and reporting results in this specific situation.

It is a fundamental value of the surgical profession to improve care for its patients. In the last 100 years, the principles of prospective quality improvement have started to work their way into the traditional method of retrospective case review in morbidity and mortality conference. This article summarizes the history of "improvement science" and its intersection with the field of surgery. It attempts to clarify the principles and jargon that may be new or confusing to surgeons with a different vocabulary and experience. This is done to bring the significant power and resources of improvement science to the traditional efforts to improve surgical care., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background and Objectives: Some topics in the clinical management of regional anesthesia in children remain controversial. To evaluate and come to a consensus regarding some of these topics, The European Society of Regional Anaesthesia and Pain Therapy (ESRA) and the American Society of Regional Anesthesia and Pain Medicine (ASRA) developed a joint committee practice advisory on pediatric regional anesthesia (PRA)., Methods: Representatives from both ASRA and ESRA comprised the joint committee practice advisory on PRA. Evidence-based recommendations were based on a systematic search of the literature. In cases where no literature was available, expert opinion was elicited. Experts selected controversial topics in PRA., Results: The performance of PRA under general anesthesia or deep sedation is associated with acceptable safety and should be viewed as the standard of care (Evidence B2 and Evidence B3). Because of the difficulty interpreting a negative test dose, the use of test dosing should remain discretionary (Evidence B4). The use of either air-loss of resistance or saline-loss of resistance techniques is supported by expert opinion, but the literature supporting one technique over the other is sparse and controversial; when used appropriately, each technique may be safely used in children. There are no current evidence-based data that the use of RA increases the risk for acute compartment syndrome or delays its diagnosis in children., Conclusions: High-level evidence is not yet available for the topics evaluated, and most recommendations are based on Evidence B studies. The ESRA/ASRA recommendations intend to provide guidance for the safe practice of regional anesthesia in children.

The Nuclear Medicine Global Initiative (NMGI) was formed in 2012 and consists of 13 international organizations with direct involvement in nuclear medicine. The underlying objectives of the NMGI were to promote human health by advancing the field of nuclear medicine and molecular imaging, encourage global collaboration in education, and harmonize procedure guidelines and other policies that ultimately lead to improvements in quality and safety in the field throughout the world. For its first project, the NMGI decided to consider the issues involved in the standardization of administered activities in pediatric nuclear medicine. This article presents part 1 of the final report of this initial project of the NMGI. It provides a review of the value of pediatric nuclear medicine, the current understanding of the carcinogenic risk of radiation as it pertains to the administration of radiopharmaceuticals in children, and the application of dosimetric models in children. A listing of pertinent educational and reference resources available in print and online is also provided. The forthcoming part 2 report will discuss current standards for administered activities in children and adolescents that have been developed by various organizations and an evaluation of the current practice of pediatric nuclear medicine specifically with regard to administered activities as determined by an international survey of nuclear medicine clinics and centers. Lastly, the part 2 report will recommend a path forward toward global standardization of the administration of radiopharmaceuticals in children., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

This paper describes how cooperation among international organizations, as modeled in Europe, can work to improve imaging safety and standards for children throughout the world. This is demonstrated in the mechanisms employed in a large-scale multi-national study on CT imaging safety practices described elsewhere in this issue of Pediatric Radiology. Here we learn approaches through which CT safety standards have been achieved and the international resources available to help in standardizing safety practices in medical imaging. There are unique strengths of the approach in Europe, which has mandatory requirements on member states to facilitate strengthening of radiation protection. Most countries have national regulatory mechanisms for radiation protection in medicine. International organizations play a significant role in supporting projects in lower-resource countries such that a large proportion of radiologic professionals in low-resource countries are trained through assistance by these organizations. Many of these international organizations make it possible for professionals worldwide to download free training material. Collaboration among international organizations and the Image Gently campaign toward consensus with regard to radiation protection can go further than individual opinions in promoting a higher standard of radiation protection around the world.

The requirements for and conditions of subspecialty training in paediatric gastroenterology, hepatology, and nutrition (PGHN) are rather variable across European countries. The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) agreed on a training syllabus aimed to foster a harmonised European PGHN curriculum and to support national PGHN societies and governmental bodies to promote and establish high-quality training programmes and levels of certification in the field. The document provides PGHN training prerequisites and objectives and the basic knowledge elements to acquire the clinical, technical, and management skills needed. Guidelines and instruments for self-monitoring and appraisal are proposed, and a logbook is available online. These training standards are a first step towards a European certification and recognition as a specialist in PGHN.

Background: There is increasing focus on the problems involved in the transition and transfer of young adult patients from paediatric to adult renal units. This situation was addressed by the 2011 International Pediatric Nephrology Association/International Society of Nephrology (IPNA/ISN) Consensus Statement on transition., Methods: We performed a survey of transition practices of 15 paediatric nephrology units across Europe 2 years after publication of the consensus statement., Results: Two thirds of units were aware of the guidelines, and one third had integrated them into their transition practice. Forty-seven per cent of units transfer five or fewer patients with chronic kidney disease (CKD) stage 5 per year to a median of five adult centres, with higher numbers of CKD stages 2-4 patients. Seventy-three per cent of units were required by the hospital or government to transfer patients by a certain age. Eighty per cent of units commenced transition planning after the patient turned 15 years of age and usually within 1-2 years of the compulsory transfer age. Forty-seven per cent of units used a transition or transfer clinic. Prominent barriers to effective transition were patient and parent attachment to the paediatric unit and difficulty in allowing the young person to perform self-care., Conclusions: Whereas awareness of the consensus statement is suboptimal, it has had some impact on practice. Adult nephrologists receive transferred patients infrequently, and the process of transition is introduced too late by paediatricians. Government- and hospital-driven age-based transfer policies distract focus from the achievement of competencies in self care. Variable use of transition clinics, written patient information and support groups is probably due to economic and human-resource limitations. The consensus statement provides a standard for evolving and evaluating transition policies jointly agreed upon by paediatric and adult units.

Background: According to a recent survey, the 2009 North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition-European Society for Pediatric Gastroenterology, Hepatology, and Nutrition gastroesophageal reflux guidelines are poorly adhered to by European primary care pediatricians. The main issue raised from the survey was the prescription of unnecessary acid suppressive medications, especially in infants. No inquiry into the reasons was made. The primary objective of the present study was to assess the applicability of the guidelines in European primary care pediatricians undergoing specific trainings., Methods: One hundred pediatricians involved in the previous survey agreed to participate and were randomly divided into 2 groups: one group was trained in the guidelines through an online podcast and the other group was trained through a synopsis. During the following 3 months, each involved pediatrician was asked to enroll every consecutive infant, child, or adolescent with suggestive reflux symptoms. For every enrolled patient, pediatricians filled in a report concerning their diagnostic and therapeutic choices., Results: A total of 382 patients (boys/girls 186/196, infants/children/adolescents 194/123/65) were enrolled by pediatricians. Infants with unexplained crying and/or distressed behavior who were prescribed proton-pump inhibitors were 3.7% compared with 45.2% of the survey data obtained before the training (P < 0.05). Infants with uncomplicated recurrent regurgitation and vomiting who were prescribed proton-pump inhibitors were 4.5% against 37.1% of the baseline survey data (P < 0.05). The overall rate of children managed in full compliance with the guidelines was 46.1% after the training compared with 1.8% before the training (P < 0.05). No significant differences were seen between pediatricians from podcast and synopsis group., Conclusions: The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition-European Society for Pediatric Gastroenterology, Hepatology, and Nutrition gastroesophageal reflux guidelines have good applicability, despite that they are presently poorly adhered to by European primary care pediatricians. Simple, inexpensive trainings were proven to be effective in increasing adherence by pediatricians. The increase in compliance clearly favors the role of continuous medical education through simple educational tools and subsequent assessment of practice.

The European Society of Paediatric Radiology Uroradiology Task Force and the ESUR Paediatric Work Group jointly publish guidelines for paediatric urogenital imaging. Two yet unaddressed topics involving patient safety and imaging load are addressed in this paper: renal biopsy in childhood and imaging of the neonatal genital tract, particularly in girls. Based on our thorough review of literature and variable practice in multiple centers, procedural recommendations are proposed on how to perform renal biopsy in children and how to approach the genital tract in (female) neonates. These are statements by consensus due to lack of sufficient evidence-based data. The procedural recommendation on renal biopsy in childhood aims at improving patient safety and reducing the number of unsuccessful passes and/or biopsy-related complications. The recommendation for an imaging algorithm in the assessment of the neonatal genital tract focuses on the potential of ultrasonography to reduce the need for more invasive or radiating imaging, however, with additional fluoroscopy or MRI to be used in selected cases. Adherence to these recommendations will allow comparable data and evidence to be generated for future adaptation of imaging strategies in paediatric uroradiology.

The relationship between suboptimal use of antimicrobials and antimicrobial resistance has become increasingly clear. Despite significant international effort aimed at reducing inappropriate antimicrobial prescribing in hospitals, antimicrobial resistance remains a major public health threat. Antimicrobial Stewardship Programs (ASPs) comprise a series of measures aimed at optimizing the use of antimicrobials, while improving the quality of patient care and promoting cost-effectiveness. This discussion article aims to summarize some of the approaches that have been used in neonatal and pediatric ASPs, with a particular focus on the European healthcare setting. Current evidence demonstrates neonatal and pediatric ASPs to be safe, practical to implement, generally cost-effective and possibly associated with a reduction in antimicrobial resistance rates. This review identified that, despite the recognized need for additional evidence and information on implementation, published data on pediatric ASPs derives mainly from the United States, with very few published reports on formal ASPs in European children's hospitals. Consequently, the optimal method of implementation remains unknown within a European setting. Future research needs to include novel study designs on how best to introduce ASPs, monitoring of clinically relevant outcomes and cost-effectiveness with improved measurement of the impact on antimicrobial resistance.

Objective: We aimed to study current practices in growth monitoring by European primary care paediatricians and to explore their perceived needs in this field., Methods: We developed a cross-sectional, anonymous on-line survey and contacted primary care paediatricians listed in national directories in the 18 European countries with a confederation of primary care paediatricians. Paediatricians participated in the survey between April and September 2011., Results: Of the 1,198 paediatricians from 11 European countries (response rate 13%) who participated, 29% used the 2006 World Health Organization Multicentre Growth Reference Study growth charts, 69% used national growth charts; 61% used software to draw growth charts and 79% did not use a formal algorithm to detect abnormal growth on growth charts. Among the 21% of paediatricians who used algorithms, many used non-algorithmic simple thresholds for height and weight and none used the algorithms published in the international literature. In all, 69% of paediatricians declared that a validated algorithm to monitor growth would be useful in daily practice. We found important between-country variations., Conclusion: The varied growth-monitoring practices declared by primary care paediatricians reveals the need for standardization and evidence-based algorithms to define abnormal growth and the development of software that would use such algorithms.

Background: Wide variation exists in reported prevalence estimates and management standards of developmental dysplasia of the hip (DDH). Discrepancies in diagnosticians' opinions may explain some of this variation., Questions/purposes: We sought to determine (1) the consistency with which pediatric orthopaedic surgeons rate the importance of diagnostic criteria for DDH, and (2) whether there were geographic differences in how the diagnostic criteria were rated by surgeons., Methods: One hundred ninety-seven of 220 members of the European Paediatric Orthopaedic Society and 100 of 148 members of the British Society of Children's Orthopaedic Surgery treating children with DDH participated in this cross-sectional study across 35 countries (15 regions). Each rated 37 items in four domains that specialists previously had identified as the most important features associated with DDH in early infancy. We determined consistency using the intraclass correlation coefficient (ICC; two-way random-effects model) interpreted as poor (0-0.40), acceptable (0.41-0.74), or good (≥ 0.75)., Results: Poor consistency among surgeons was found in rating the 37 diagnostic criteria (ICC, 0.33; 95% CI, 0.24-0.45). Consistency was poor for three domains (patient characteristics/history: ICC, 0.29; 95% CI, 0.16-0.58; ultrasound: ICC, 0.26; 95% CI, 0.14-0.52; radiography: ICC, 0.34; 95% CI, 0.12-0.95) and acceptable for one (clinical examination: ICC, 0.50; 95% CI, 0.33-0.73). Surgeons in particular regions appeared to have a concept of DDH diagnosis that distinguished them from specialists of other regions; consistency in eight regions was greater (ICC ≥ 0.40) than consistency among all 15 regions., Conclusions: The consistency of specialists in rating diagnostic criteria for DDH was lower than expected, and there was considerable geographic variation in terms of how specialists assigned importance ratings of the diagnostic criteria; these findings are somewhat counterintuitive, given the frequency with which this condition is diagnosed. These inconsistencies could explain, partly, the widely differing prevalence estimates and management standards of DDH.

Purpose: Radiation therapy is important for local control in neuroblastoma. This study reviewed the compliance of plans with the radiation therapy guidelines of the International Society of Paediatric Oncology (Europe) Neuroblastoma Group (SIOPEN) High-Risk Trial protocol., Methods and Materials: The SIOPEN trial central electronic database has sections to record diagnostic imaging and radiation therapy planning data. Individual centers may upload data remotely, but not all centers involved in the trial chose to use this system. A quality scoring system was devised based on how well the radiation therapy plan matched the protocol guidelines, to what extent deviations were justified, and whether adverse effects may result. Central review of radiation therapy planning was undertaken retrospectively in 100 patients for whom complete diagnostic and treatment sets were available. Data were reviewed and compared against protocol guidelines by an international team of radiation oncologists and radiologists. For each patient in the sample, the central review team assigned a quality assurance score., Results: It was found that in 48% of patients there was full compliance with protocol requirements. In 29%, there were deviations for justifiable reasons with no likely long-term adverse effects resulting. In 5%, deviations had occurred for justifiable reasons, but that might result in adverse effects. In 1%, there was a deviation with no discernible justification, which would not lead to long-term adverse events. In 17%, unjustified deviations were noted, with a risk of an adverse outcome resulting., Conclusions: Owing to concern over the proportion of patients in whom unjustified deviations were observed, a protocol amendment has been issued. This offers the opportunity for central review of radiation therapy plans before the start of treatment and the treating clinician a chance to modify plans., (Copyright © 2013 Elsevier Inc. All rights reserved.)

'SWEET' is an acronym standing for 'Better control in pediatric and adolescent diabeteS: Working to crEate CEnTers of Reference (CORs)' and is based on a partnership of established national and European diabetes organizations such as International Diabetes Federation, Federation of European Nurses in Diabetes, and Primary Care Diabetes Europe (PCDE, www.sweet-project.eu). A three-level classification of centers has been put forward. In addition to centers for local care, SWEET collaborating centers on their way to being a COR have been defined. Peer-audited CORs with a continuous electronic documentation of at least 150 pediatric patients with diabetes treated by a multidisciplinary team based on the International Society for Pediatric and Adolescent Diabetes (ISPAD) Clinical Practice recommendations have been created in 12 European countries. In 2011, they cared for between 150 to more than 700 youth with diabetes with an average hemoglobin A1c between 7.6 and 9.2%. Although these clinics should not be regarded as representative for the whole country, the acknowledgment as COR includes a common objective of targets and guidelines as well as recognition of expertise in treatment and education at the center. In a first step, the SWEET Online platform allows 12 countries using 11 languages to connect to one unified diabetes database. Aggregate data are de-identified and exported for longitudinal health and economic data analysis. Through their network, the CORs wish to obtain political influence on a national and international level and to facilitate dissemination of new approaches and techniques. The SWEET project hopes to extend from the initial group of centers within countries, throughout Europe, and beyond with the help of the ISPAD network., (© 2012 John Wiley & Sons A/S.)

Introduction: ISPAD guidelines recommend age appropriate diabetes education concepts for young patients and their families as well as tools for nutritional management, psychosocial assessment, and psychological advice but their implementation in Europe is presently unknown., Methods: On the basis of a structured survey among the European SWEET members information on established tools and programs in national languages were analyzed using an extensive literature and desk search. These were differentiated according to five age-groups and five target groups (young people with diabetes, parents, and other close relations, carers in school and nursery, and healthcare professionals)., Results: Responses and original tools were received from 11 SWEET countries reflecting the European status in 2011. More or less structured information for parents, close relations, and carers in school or nursery are available in all 11 participating countries. However, only two countries followed the recommendations of having published a structured, curriculum lead, and evaluated program for different age-groups and carers. One of these was evaluated nationwide and funded by the respective National Health Care System after accreditation. In addition a huge variety of creative tools, e.g., booklets, leaflets, games, videos, and material for educating children of different age-groups and their parents are available - but most of them are not linked to a structured education program., Conclusions: Harmonizing and integrating these materials into quality assured structured holistic national education programs will be an important future task for the ongoing SWEET project. A comprehensive European diabetes educational toolbox is aimed to be published and continuously updated on the SWEET website., (© 2012 John Wiley & Sons A/S.)

Two new recommendations of the European Society of Radiology task force and the European Society of Uroradiology workgroup on paediatric uroradiology are presented. One deals with diagnostic imaging in children after trauma to the urinary tract-renal trauma, in particular. The other concerns the evaluation of suspected renal hypertension. Available data in the paediatric literature are either unsatisfactory or controversial for both of these clinical settings. Therefore, the following consensus-based proposals aim at outlining effective imaging algorithms to reduce invasive imaging procedures while optimising diagnostic accuracy. The objective of following a more uniform imaging approach is to facilitate future meta-analysis as well as multicentre and other more evidence-based studies. The practise in paediatric radiology is typically based on local availability and on the limitations of professional expertise and equipment, balanced against the perceived needs of the individual child. Although this is unlikely to change in the near future, it does not release the physicians in charge of diagnostic imaging from their responsibility in choosing and providing state-of-the-art imaging and management protocols that are adapted specifically for use in children.

Over the past decades, considerable legislative effort has been made to facilitate and encourage clinical research in the European Union (EU). Hereby, specific attention has been paid to the urgent need to conduct research in minors. In this article, we will analyze the regulation that currently governs pediatric clinical research conduct at the supranational level of the EU and at the level of individual EU member states. Our analysis will focus on the way in which the national and supranational legal frameworks address five ethical issues that are specific to pediatric clinical research: (a) informed consent, (b) the necessity to conduct research in minor subjects, (c) the interests of the subject concerned, (d) the risks and burdens involved, and (e) the pediatric expertise of protocol review committees. We conclude by discussing the harmonization and diversification of the legal requirements that govern pediatric clinical research in the EU., (Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

The term "off-label use of drugs in children" is common to current medical practice. A look into the historical context helps to elucidate the framework for the use of medicines in children. Proper drug labels are relatively new in history. They emerged half a century ago when U.S. legislation forced manufacturers to prove the safety and efficacy of drugs by adequate clinical trials. Today pharmaceutical progress is so obvious and well established that the discrepancy between its benefit for adults as compared to children started to be perceived by champions in different institutions. There is an increased understanding of the child's physiology during developmental growth, of the maturation of enzyme systems, of the pharmacokinetics and pharmacodynamics and of the differences in disease processes. The involved institutions include legislators, government, regulatory authorities, academic scientists, pharmaceutical companies, the WHO, to name just the most prominent ones, but there are many more. Driving forces for the improvement of medicines for children include societal priorities, the involvement of science, the mission of regulatory authorities the role of clinical pharmacologists, paediatricians, and the characteristics of our market-driven economy with its chaotic, contradictory and lively elements. We do not live in an ideal world, but there is progress, and children are likely to benefit from it.