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(1) Autism spectrum disorder (ASD) belongs to the group of complex developmental disorders. Novel studies have suggested that genetic and environmental factors equally affect the risk of ASD. Identification of environmental factors involved in the development of ASD is therefore crucial for a better understanding of its etiology. Whether there is a causal link between trace elements, brain magnetic resonance imaging (MRI), and ASD remains a matter of debate and requires further studies. (2) In the prospective part of the study, we included 194 children, including an age-matched control group; in the retrospective study, 28 children with available MRI imaging were included. All children had urine analysis of trace elements performed. In those with available brain MRI, linear indexes for the ventricular volumes were measured and calculated. (3) We found the highest vanadium, rubidium, thallium, and silver levels in children with ASD. These elements also correlated with the estimated ventricular volume based on MRI indexes in children with ASD in the subanalysis. However, the severity of the deficits did not correlate with brain MRI indexes of our elements, except negatively with magnesium. (4) Trace elements have an impact on children with ASD, but further multi-centric studies are needed to explain the pathophysiological mechanisms.
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Transtorno do Espectro Autista , Imageamento por Ressonância Magnética , Oligoelementos , Humanos , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/metabolismo , Masculino , Oligoelementos/metabolismo , Imageamento por Ressonância Magnética/métodos , Feminino , Criança , Pré-Escolar , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/patologia , Estudos Retrospectivos , Estudos Prospectivos , Estudos de Casos e ControlesRESUMO
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.
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AIM: To explore the perspectives of cerebral palsy (CP) experts on access to healthcare and an analysis of socioeconomic and environmental determinants impacting young individuals with CP in Europe. METHOD: Cross-sectional survey designed by a convenience multi-disciplinary panel of invited experts and completed by clinicians, researchers and opinions leaders in the field of CP. RESULTS: Fifty-eight experts (response rate 85 %) from 39 regions in 26 European countries completed the survey. All countries provide care and financing through public systems. Long waiting lists were reported (mean 3 mo, range 1-12 mo), depending on type of specialist care and place of residence. Although diagnostic and therapeutic services were available, access within countries/regions were unevenly distributed, with children receiving better care than adults. Most experts reported a lack of transition services, although improvement is expected (62 % of responses). Hip and malnutrition surveillance, as well as educational and recreational activities were variably available. Public transportation, accessible roads and pavements, and urban green spaces for persons with disabilities were more available in larger cities. Overall, only 57 % of responders felt that most patients had adequate access to healthcare. CONCLUSION: The survey of CP experts' perspectives from the majority of European countries indicates discrepancies in the availability and accessibility of healthcare needed by people with CP and nonuniform implementation of policies across Europe.
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Aicardi-Goutières syndrome (AGS) is a rare genetic early-onset progressive encephalopathy with variable clinical manifestations. The IFIH1 mutation has been confirmed to be responsible for type I interferon production and activation of the Janus kinase signaling pathway. We herein stress neurological observations and neuroimaging findings in a severe case report of an infant with AGS type 7 due to an IFIH1 mutation who was diagnosed in the first month of life. We also review neurological characteristics of IFIH1 mutations through recent literature.
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Background and objectives: In children requiring electroencephalography (EEG), sleep recording can provide crucial information. As EEG recordings during spontaneous sleep are not always possible, pharmacological sleep-inducing agents are sometimes required. The aim of the study was to evaluate safety and efficacy of melatonin (Mel) and dexmedetomidine (Dex; intranasal and sublingual application) for sleep induction prior to EEG. Methods: In this prospective randomized study, 156 consecutive patients aged 1-19 years were enrolled and randomized by draw into melatonin group (Mel; n = 54; dose: 0.1â mg/kg), dexmedetomidine (Dex) sublingual group (DexL; n = 51; dose: 3â mcg/kg) or dexmedetomidine intranasal group (DexN; n = 51; dose: 3â mcg/kg). We compared the groups in several parameters regarding efficacy and safety and also carried out a separate analysis for a subgroup of patients with complex behavioral problems. Results: Sleep was achieved in 93.6% of participants after the first application of the drug and in 99.4% after the application of another if needed. Mel was effective as the first drug in 83.3% and Dex in 99.0% (p < 0.001); in the subgroup of patients with complex developmental problems Mel was effective in 73.4% and Dex in 100% (p < 0.001). The patients fell asleep faster after intranasal application of Dex than after sublingual application (p = 0.006). None of the patients had respiratory depression, bradycardia, desaturation, or hypotension. Conclusions: Mel and Dex are both safe for sleep induction prior to EEG recording in children. Dex is more effective compared to Mel in inducing sleep, also in the subgroup of children with complex behavioral problems. Clinical Trial Registration: Dexmedetomidine and Melatonin for Sleep Induction for EEG in Children, NCT04665453.
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BACKGROUND: Transition from child-centered to adult-centered healthcare is a gradual process that addresses the medical, psychological, and educational needs of young people in the management of their autonomy in making decisions about their health and their future clinical assistance. This transfer is challenging across all chronic diseases but can be particularly arduous in rare neurological conditions. AIM: To describe the current practice on the transition process for young patients in centers participating in the European Reference Network for Rare Neurological Diseases (ERN-RND). METHODS: Members of the ERN-RND working group developed a questionnaire considering child-to-adult transition issues and procedures in current clinical practice. The questionnaire included 20 questions and was sent to members of the health care providers (HCPs) participating in the network. RESULTS: Twenty ERN-RND members (75% adult neurologists; 25% pediatricians; 5% nurses or study coordinators) responded to the survey, representing 10 European countries. Transition usually occurs between 16 and 18 years of age, but 55% of pediatric HCPs continue to care for their patients until they reach 40 years of age or older. In 5/20 ERN-RND centers, a standardized procedure managing transition is currently adopted, whereas in the remaining centers, the transition from youth to adult service is usually assisted by pediatricians as part of their clinical practice. CONCLUSIONS: This survey demonstrated significant variations in clinical practice between different centers within the ERN-RND network. It provided valuable data on existing transition programs and highlighted key challenges in managing transitions for patients with rare neurological disorders.
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Atenção à Saúde , Doenças do Sistema Nervoso , Adulto , Adolescente , Humanos , Criança , Inquéritos e Questionários , Europa (Continente) , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/terapia , Doenças Raras/diagnóstico , Doenças Raras/terapiaRESUMO
Challenges exist in access to high-quality care for insomnia disorder. After the recent publication of a clinical practice guideline on behavioral and psychological treatments for insomnia in adults, the American Academy of Sleep Medicine (AASM) hosted a 1-day virtual Insomnia Summit in September 2022 to discuss improving care for patients with insomnia disorder. Fifty participants representing a variety of organizations (eg, medical, psychological, and nursing associations; patient advocacy groups; and federal institutions) participated in the event. Videos highlighting patient perspectives on insomnia and an overview of current insomnia disorder treatment guidelines were followed by thematic sessions, each with 3 to 4 brief, topical presentations by content experts. Breakout groups were used to brainstorm and prioritize issues in each thematic area. Top barriers to care for insomnia disorder include limited access, limited awareness of treatment options, low perceived value of insomnia treatment, and an insufficient number of trained clinicians. Top facilitators of high-quality care include education and awareness, novel care models to increase access, expanding the insomnia patient care workforce, incorporating research into practice, and increasing reimbursement for psychotherapies. Priorities for the future include increasing awareness among patients and providers, increasing the number of skilled behavioral sleep medicine providers, increasing advocacy efforts to address insurance issues (eg, billing, reimbursement, and performance measures), and working collaboratively with multidisciplinary organizations to achieve common goals. These priorities highlight that goals set to improve accessible, high-quality care for insomnia disorder will require sustained, coordinated efforts to increase awareness, improve reimbursement, and grow the necessary skilled health care workforce. CITATION: Schotland H, Wickwire E, Aaronson RM, et al. Increasing access to evidence-based insomnia care in the United States: findings from an American Academy of Sleep Medicine stakeholder summit. J Clin Sleep Med. 2024;20(3):455-459.
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Médicos , Distúrbios do Início e da Manutenção do Sono , Adulto , Humanos , Estados Unidos , Distúrbios do Início e da Manutenção do Sono/terapia , Academias e Institutos , Pessoal de Saúde , SonoRESUMO
Phosphoribosylpyrophosphate synthetase 1 (PRS-I) is an enzyme involved in nucleotide metabolism. Pathogenic variants in the PRPS1 are rare and PRS-I deficiency can manifest as three clinical syndromes: X-linked non-syndromic sensorineural deafness (DFN2), X-linked Charcot-Marie-Tooth neuropathy type 5 (CMTX5) and Arts syndrome. We present a Slovenian patient with PRS-I enzyme deficiency due to a novel pathogenic variant - c.424G > A (p.Val142Ile) in the PRPS1 gene, who presented with gross motor impairment, severe sensorineural deafness, balance issues, ataxia, and frequent respiratory infections. In addition, we report the findings of a systemic literature review of all described male cases of Arts syndrome and CMTX5 as well as intermediate phenotypes. As already proposed by other authors, our results confirm PRS-I deficiency should be viewed as a phenotypic continuum rather than three separate syndromes because there are multiple reports of patients with an intermediary clinical presentation.
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[This corrects the article DOI: 10.3389/fped.2022.856615.].
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A new type of research has emerged with United States and European Union pediatric laws that request/demand separate clinical studies for vaccines and drugs in minors less than 18 years of age. Physiologically, minors mature before their 18th birthday. Medicine treats the body, not the administrative status. Many "pediatric" studies are performed in minors that bodily are no longer children, which makes them pointless. Traditional malpractice litigation in clinical research involves patients that were harmed in clinical studies. In the new type of "pediatric" studies, drugs known to work in humans are retested, pretending that "children" are uniquely different, which is incorrect. Minors are not another species. Patients are not treated at all (placebo group) or below standard-of-care (comparison to outdated treatment). Pediatric laws are the law, but not a free pass for harming patients. Where "pediatric" studies violate accepted norms of medical practice, lawyers should be aware of this challenge at the interface of medicine and law.
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Pesquisa Biomédica , Maus-Tratos Infantis , Imperícia , Criança , Humanos , Estados Unidos , Advogados , União EuropeiaRESUMO
Determining the most effective insomnia medication for patients may require therapeutic trials of different medications. In addition, medication side effects, interactions with co-administered medications, and declining therapeutic efficacy can necessitate switching between different insomnia medications or deprescribing altogether. Currently, little guidance exists regarding the safest and most effective way to transition from one medication to another. Thus, we developed evidence-based guidelines to inform clinicians regarding best practices when deprescribing or transitioning between insomnia medications. Five U.S.-based sleep experts reviewed the literature involving insomnia medication deprescribing, tapering, and switching and rated the quality of evidence. They used this evidence to generate recommendations through discussion and consensus. When switching or discontinuing insomnia medications, we recommend benzodiazepine hypnotic drugs be tapered while additional CBT-I is provided. For Z-drugs zolpidem and eszopiclone (and not zaleplon), especially when prescribed at supratherapeutic doses, tapering is recommended with a 1-2-day delay in administration of the next insomnia therapy when applicable. There is no need to taper DORAs, doxepin, and ramelteon. Lastly, off-label antidepressants and antipsychotics used to treat insomnia should be gradually reduced when discontinuing. In general, offering individuals a rationale for deprescribing or switching and involving them in the decision-making process can facilitate the change and enhance treatment success.
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Biomass burning (BB) is a major source of aerosols that remain the most uncertain components of the global radiative forcing. Current global models have great difficulty matching observed aerosol optical depth (AOD) over BB regions. A common solution to address modelled AOD biases is scaling BB emissions. Using the relationship from an ensemble of aerosol models and satellite observations, we show that the bias in aerosol modelling results primarily from incorrect lifetimes and underestimated mass extinction coefficients. In turn, these biases seem to be related to incorrect precipitation and underestimated particle sizes. We further show that boosting BB emissions to correct AOD biases over the source region causes an overestimation of AOD in the outflow from Africa by 48%, leading to a double warming effect compared with when biases are simultaneously addressed for both aforementioned factors. Such deviations are particularly concerning in a warming future with increasing emissions from fires.
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Poluentes Atmosféricos , Incêndios , Aerossóis/análise , Poluentes Atmosféricos/análise , Viés , Biomassa , Monitoramento Ambiental/métodosRESUMO
The Challenge-20 is an assessment of advanced motor skills of children with cerebral palsy. The purpose of this study was to develop age-related norms and percentile curves for the Challenge-20 with typically developing children ( n = 150, 7 through 11 years), and compare Challenge-20 scores of independently ambulatory children with CP, Gross Motor Function Classification System level I ( n = 135) and II ( n = 56) to these age norms. Younger TD children (7 years) scored lowest, and older children (11 years) scored highest on the Challenge-20 , showing similar developmental trajectories. Challenge-20 scores of 15% of children in GMFCS level I were situated above the lower 2.5th percentile curve of the typically developing children's Challenge-20 growth curve, that is, overlapping into the typically developing child zone. The Challenge-20 is sensitive to the progression of advanced gross motor skills in typically developing children. Children with cerebral palsy, GMFCS I follow similar, albeit lower, Challenge score trajectory to that of typically developing children, and in some cases come close to lower level abilities of typically developing children. The reference values with typically developing children extend the Challenge-20 's utility when assessing advanced gross motor skill of independently ambulatory children with cerebral palsy for physiotherapy intervention and physical activity planning and open the door to re-thinking more about advanced gross motor interventions for children with cerebral palsy in GMFCS levels I and II given their potential to progress along the developmental trajectory.
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Paralisia Cerebral , Destreza Motora , Criança , Humanos , Adolescente , Modalidades de Fisioterapia , Valores de ReferênciaRESUMO
The climate models of the Intergovernmental Panel on Climate Change list black carbon (BC) as an important contributor to global warming based on its radiative forcing (RF) impact. Examining closely these models, it becomes apparent that they might underpredict significantly the direct RF for BC, largely due to their assumed spherical BC morphology. Specifically, the light absorption and direct RF of BC agglomerates are enhanced by light scattering between their constituent primary particles as determined by the Rayleigh-Debye-Gans theory interfaced with discrete dipole approximation and recent relations for the refractive index and lensing effect. The light absorption of BC is enhanced by about 20% by the multiple light scattering between BC primary particles regardless of the compactness of their agglomerates. The resulting light absorption agrees very well with the observed absorption aerosol optical depth of BC. ECHAM-HAM simulations accounting for the realistic BC morphology and its coatings reveal high direct RF = 3-5 W/m2 in East, South Asia, sub-Sahara, western Africa, and the Arabian peninsula. These results are in agreement with satellite and AERONET observations of RF and indicate a regional climate warming contribution by 0.75-1.25 °C, solely due to BC emissions.
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Background and Objectives: To report on the novel association of biallelic variant in atonal basic helix-loop-helix transcription factor 1 (ATOH1) gene and pontocerebellar hypoplasia (PCH), severe global developmental delay, intellectual disability, and hearing loss in a family with 2 affected siblings. Methods: A detailed clinical assessment and exome sequencing of peripheral blood sample were performed. Segregation analysis with Sanger sequencing and structural modeling of the variant was performed to support the pathogenicity of the variant. Results: A homozygous missense variant (NM_005172.1:c.481C>G) in the ATOH1 gene was identified in the proband and his affected sister. The segregation analysis subsequently confirmed its segregation with an apparently recessive PCH in this family. ATOH1 encodes for the atonal basic helix-loop-helix (bHLH) transcription factor 1, a core transcription factor in the developing cerebellum, brainstem, and dorsal spinal cord, and in the ear. The identified variant results in the p.(Arg161Gly) amino acid substitution in the evolutionarily conserved DNA-binding bHLH domain of the ATOH1 protein. Biallelic missense variants in this domain were previously reported to result in disordered cerebellar development and hearing loss in animal models. In silico homology modeling revealed that p.Arg161Gly in ATOH1 protein probably disrupts a salt bridge with DNA backbone phosphate and increases the flexibility of the bHLH helix-both of which together affect the binding capability of the bHLH domain to the DNA. Discussion: Based on the sequencing results and evidence from structural modeling of the identified variant, as well as with previous reports of ATOH1 gene disruption, we conclude that ATOH1 may represent a novel candidate gene associated with the phenotype of PCH, global developmental delay, and hearing loss in humans.
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Introduction: Prediction of outcome in newborns with hypoxic-ischemic encephalopathy (HIE) has been modulated by hypothermia treatment (HT). We assessed the predictive value of diagnostic methods commonly used in neonates with HIE for short-term neurodevelopmental outcome and long-term neurological outcome. Materials and Methods: This longitudinal cohort study followed up 50 term newborns who underwent HT after HIE between July 2006 and August 2015, until preschool age. We estimated sensitivity and specificity for short-term neurodevelopmental outcome at 18 months and long-term neurological outcome at five years based on Amiel-Tison Neurological Assessment (ATNA), electroencephalography (EEG), and magnetic resonance imaging (MRI) performed in the neonatal period. Results: The accuracy of all neonatal methods tested was higher for long-term neurological outcome compared to the predictive accuracy for short-term neurodevelopmental outcome at 18-24 months. Sensitivity and specificity in predicting unfavorable long-term neurological outcome were: MRI (sensitivity 1.0 [95%CI 0.96-1.0]; specificity 0.91 [95%CI 0.86-1.0]), EEG (sensitivity 0.94 [95%CI 0.71-1.0]; specificity 1.0 [95% CI 0.89-1.0]), and ATNA (sensitivity 0.94 [95%CI 0.71-1.0]; specificity 0.91 [95%CI 0.76-0.98]). Conclusion: MRI is a powerful predictor of long-term neurological outcome when performed in the first week after HIE in HT treated infants, as are EEG and ATNA performed in the second or third week postnatally.
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Perinatal hypoxic-ischemic brain injury is a major cause of non-progressive neurological deficits in children. Dysmature patterns can be seen in newborns' electroencephalograms (EEGs) and may have prognostic value for long-term outcomes. OBJECTIVE: To investigate the prognostic value of dysmature EEG patterns in term or near-term newborns. METHODS: Neonates with dysmature patterns in their first neonatal EEG, assessed during a 6-year period from January 2010 to December 2015, were included in the study. Their outcomes at their follow-ups in June 2019 (at the age of 3 years or more) were assessed, and the presence of neurological deficits and/or epilepsy was noted. RESULTS: We identified 347 neonates with video-EEG recordings during the observed period, in which 10 neonates had dysmature patterns in their first EEG. Eight were born at term and two were born late preterms, born at the 35 and 36-week gestational age. The reasons for admission were HIE grade I in 2 patients, grade II in 6 neonates, and heart problems in 2 patients. The second EEG was recorded at different time intervals, in 7 infants between 1 and 6 weeks; three infants had second EEG much later and were excluded from the study. Six of seven infants showed normal background activity (BA), and five had sharp waves over different regions, all six had normal developmental outcomes. One child with dysrhythmic pattern in the second EEG was diagnosed with genetic encephalopathy, developed spastic cerebral palsy and died due to severe pneumonia at the age of 6 years. CONCLUSION: Dysmature patterns may reflect transitory brain dysfunctions. Neonatal EEG tests remain reliable and important diagnostic tool in the very first weeks of life, particularly due to the availability of sequential EEG recordings and interpretations.
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Lesões Encefálicas , Doenças do Recém-Nascido , Biomarcadores , Encéfalo , Criança , Pré-Escolar , Eletroencefalografia , Idade Gestacional , Humanos , Lactente , Recém-NascidoRESUMO
INTRODUCTION: Regulatory authorities recognize two human populations: adults and children defined as <18 years. For drug approval, they demand separate studies. But humans mature slowly during puberty. The 18th birthday is an administrative limit that does not correspond to a physiological change. Separate drug approval before/after the 18th birthday reflects the children-are-therapeutic-orphans concept that emerged after 1962. The Food and Drug Administration (FDA) has backed away from this concept for antiepileptic drugs, but sticks to it in other areas. In contrast, the European Medicines Agency (EMA) is continuously expanding its demand for 'pediatric' studies. Parents hesitate increasingly to let their children participate in questionable studies. AREAS COVERED: Neurologists challenge the children-are-therapeutic-orphans mantra. Young patients do not need separate proof of efficacy & safety, but appropriate dosing recommendations. Minors should be treated as human beings, instead of being abused in questionable studies. EXPERT OPINION: Young patients with multiple sclerosis and other neurological diseases deserve studies with therapeutic intentions. 'Pediatric' careers have emerged in academia, regulatory authorities, and pharmaceutical companies. Institutional Review Boards/ Ethics Committees should suspend questionable 'pediatric' studies and reject newly submitted ones. The medical professions should distance themselves from questionable 'pediatric' research that reflects massive conflicts of interest.
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Neurologia , Adulto , Criança , Humanos , Estados Unidos , United States Food and Drug AdministrationRESUMO
BACKGROUND: Cerebral palsy (CP) is a common cause of physical impairment in children, especially in newborns who are small for gestational age (SGA). AIMS: The aim of our study was to investigate the association between birth weight and the risk of developing CP, controlling for gestational age and plurality. STUDY DESIGN: This retrospective, observational, case-control study was based on Slovenian Registry of Cerebral Palsy (SRCP) and Slovenian National Perinatal Information System (NPIS) data for the period 2002 to 2010. SUBJECTS: For each pregnancy that resulted in the birth of the newborn(s) who later developed CP (n = 254), three pregnancies with newborns who did not develop CP (n = 762) were selected and matched for gestational age and plurality. OUTCOME MEASURES: Diagnosis of CP was made at age 5 years or older by a developmental pediatrician trained in child neurology or a child neurologist using standard measures. RESULTS: Risk of CP increased progressively as birth weight percentiles fell below the 50th centile, with children in the lowest percentiles at greatest risk. Birth weight percentiles traditionally classified as SGA were an independent risk factor for developing CP, with an odds ratio of 2.43 (95% confidence interval 1.57, 3.73). CONCLUSIONS: The results of this study suggest that the risk for developing CP is inversely related to birth weight, even at birth weights that do not meet the standard definitions of SGA. SYNOPSIS - STUDY QUESTION: Does birth weight represent a potential risk factor for the development of cerebral palsy (CP) when controlling for gestational age and plurality? WHAT'S ALREADY KNOWN: Newborns who are small for gestational age (SGA) are at higher risk of developing CP according to published studies. However, different definitions of SGA (birth weight below the 10th, 5th, or 3rd percentile for gestational age) have been used by researchers and clinicians, making it difficult to compare studies. WHAT THIS STUDY ADDS: This study suggests that the risk of developing CP is inversely related to birth weight, even at birth weights that do not meet standard definitions of SGA.
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Paralisia Cerebral , Peso ao Nascer , Estudos de Casos e Controles , Paralisia Cerebral/epidemiologia , Paralisia Cerebral/etiologia , Criança , Pré-Escolar , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Gravidez , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: Clinical trial sponsors spend considerable resources preparing informed consent (IC) and assent documentation for multinational paediatric clinical trial applications in Europe due to the limited and dispersed patient populations, the variation of national legal and ethical requirements, and the lack of detailed guidance. The aim of this study was to design new easy-to-use guide publicly available on European Medicines Agency's, Enpr-EMA website for all stakeholders. METHODS: Current EU legal, ethical and regulatory guidance for paediatric clinical trials were collated, analysed and divided into 30 subject elements in two tables. The European Network of Young Person's Advisory Group reviewed the data and provided specific comments. A three-level recommendation using 'traffic light' symbols was designed for four age groups of children, according to relevance and the requirements. RESULTS: A single guide document includes two tables: (1) general information and (2) trial-specific information. In the age group of 6-9 years old, 92% of the trial-specific subject elements can be or should be included in the IC discussion. Even in the youngest possible age group (2-5 years old children), the number of elements considered was, on average, 52%. CONCLUSION: The EU Clinical Trial Regulation (2014) does not contain specific requirements exclusively for paediatric clinical trials. This work is the first to extensively collate all the current legal, regulatory and ethical documentation on the IC process, together with input from adolescents. This guide may increase the ethical standards in paediatric clinical trials.