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1.
N Engl J Med ; 382(3): 233-243, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31940698

RESUMO

BACKGROUND: High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established. METHODS: In this multicenter, randomized, double-blind trial of high-dose erythropoietin, we assigned 941 infants who were born at 24 weeks 0 days to 27 weeks 6 days of gestation to receive erythropoietin or placebo within 24 hours after birth. Erythropoietin was administered intravenously at a dose of 1000 U per kilogram of body weight every 48 hours for a total of six doses, followed by a maintenance dose of 400 U per kilogram three times per week by subcutaneous injection through 32 completed weeks of postmenstrual age. Placebo was administered as intravenous saline followed by sham injections. The primary outcome was death or severe neurodevelopmental impairment at 22 to 26 months of postmenstrual age. Severe neurodevelopmental impairment was defined as severe cerebral palsy or a composite motor or composite cognitive score of less than 70 (which corresponds to 2 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition. RESULTS: A total of 741 infants were included in the per-protocol efficacy analysis: 376 received erythropoietin and 365 received placebo. There was no significant difference between the erythropoietin group and the placebo group in the incidence of death or severe neurodevelopmental impairment at 2 years of age (97 children [26%] vs. 94 children [26%]; relative risk, 1.03; 95% confidence interval, 0.81 to 1.32; P = 0.80). There were no significant differences between the groups in the rates of retinopathy of prematurity, intracranial hemorrhage, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, or death or in the frequency of serious adverse events. CONCLUSIONS: High-dose erythropoietin treatment administered to extremely preterm infants from 24 hours after birth through 32 weeks of postmenstrual age did not result in a lower risk of severe neurodevelopmental impairment or death at 2 years of age. (Funded by the National Institute of Neurological Disorders and Stroke; PENUT ClinicalTrials.gov number, NCT01378273.).


Assuntos
Eritropoetina/administração & dosagem , Lactente Extremamente Prematuro , Doenças do Prematuro/prevenção & controle , Transtornos do Neurodesenvolvimento/prevenção & controle , Encéfalo/diagnóstico por imagem , Pré-Escolar , Método Duplo-Cego , Eritropoetina/efeitos adversos , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Doenças do Prematuro/mortalidade , Masculino , Transtornos do Neurodesenvolvimento/epidemiologia , Ultrassonografia
2.
Medicine (Baltimore) ; 99(1): e18611, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895812

RESUMO

BACKGROUND: This systematic review protocol aims to examine the evidence of effectiveness and cost-effectiveness of interventions for children and adolescents with, or at risk of developing mental disorders in low- and middle-income countries (LAMICs). METHODS: We will search Medline Ovid, EMBASE Ovid, PsycINFO Ovid, CINAHL, LILACS, BDENF and IBECS. We will include randomised and non-randomised controlled trials, economic modelling studies and economic evaluations. Participants are 6 to 18 year-old children and adolescents who live in a LAMIC and who present with, or are at high risk of developing, one or more of the conditions: depression, anxiety, behavioural disorders, eating disorders, psychosis, substance abuse, autism and intellectual disabilities as defined by the DSM-V. Interventions which address suicide, self-harm will also be included, if identified during the extraction process. We will include in person or e-health interventions which have some evidence of effectiveness (in relation to clinical and/or functional outcomes) and which have been delivered to young people in LAMICs. We will consider a wide range of delivery channels (e.g., in person, web-based or virtual, phone), different practitioners (healthcare practitioners, teachers, lay health care providers) and sectors (i.e., primary, secondary and tertiary health care, education, guardianship councils). In the pilot of screening procedures, 5% of all references will be screened by two reviewers. Divergences will be resolved by one expert in mental health research. Reviewers will be retrained afterwards to ensure reliability. The remaining 95% will be screened by one reviewer. Covidence web-based tool will be used to perform screening of references and full text paper, and data extraction. RESULTS: The protocol of this systematic review will be disseminated in a peer-reviewed journal and presented at relevant conferences. The results will be presented descriptively and, if possible, meta-analysis will be conducted. Ethical approval is not needed for anonymised secondary data. CONCLUSION: the systematic review could help health specialists and other professionals to identify evidence-based strategies to deal with child and adolescents with mental health conditions.


Assuntos
Países em Desenvolvimento , Transtornos do Neurodesenvolvimento/terapia , Criança , Humanos , Transtornos do Neurodesenvolvimento/economia , Revisão Sistemática como Assunto
3.
Arch Dis Child Fetal Neonatal Ed ; 105(1): 8-13, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31036702

RESUMO

OBJECTIVE: Since therapeutic hypothermia became standard care for neonatal hypoxic-ischaemic encephalopathy (HIE), even fewer infants die or have disability at 18-month assessment than in the clinical trials. However, longer term follow-up of apparently unimpaired children is lacking. We investigated the cognitive, motor and behavioural performances of survivors without cerebral palsy (CP) cooled for HIE, in comparison with matched non-HIE control children at 6-8 years. DESIGN: Case-control study. PARTICIPANTS: 29 case children without CP, cooled in 2008-2010 and 20 age-matched, sex-matched and social class-matched term-born controls. MEASURES: Wechsler Intelligence Scales for Children, Fourth UK Edition, Movement Assessment Battery for Children, Second Edition (MABC-2) and Strengths and Difficulties Questionnaire. RESULTS: Cases compared with controls had significantly lower mean (SD) full-scale IQ (91 [10.37]vs105[13.41]; mean difference (MD): -13.62, 95% CI -20.53 to -6.71) and total MABC-2 scores (7.9 [3.26]vs10.2[2.86]; MD: -2.12, 95% CI -3.93 to -0.3). Mean differences were significant between cases and controls for verbal comprehension (-8.8, 95% CI -14.25 to -3.34), perceptual reasoning (-13.9, 95% CI-20.78 to -7.09), working memory (-8.2, 95% CI-16.29 to -0.17), processing speed (-11.6, 95% CI-20.69 to -2.47), aiming and catching (-1.6, 95% CI-3.26 to -0.10) and manual dexterity (-2.8, 95% CI-4.64 to -0.85). The case group reported significantly higher median (IQR) total (12 [6.5-13.5] vs 6 [2.25-10], p=0.005) and emotional behavioural difficulties (2 [1-4.5] vs 0.5 [0-2.75], p=0.03) and more case children needed extra support in school (34%vs5%, p=0.02) than the control group. CONCLUSIONS: School-age children without CP cooled for HIE still have reduced cognitive and motor performance and more emotional difficulties than their peers, strongly supporting the need for school-age assessments.


Assuntos
Hipotermia Induzida , Hipóxia-Isquemia Encefálica/terapia , Transtornos do Neurodesenvolvimento/diagnóstico , Estudos de Casos e Controles , Criança , Transtornos do Comportamento Infantil/diagnóstico , Compreensão , Feminino , Seguimentos , Humanos , Recém-Nascido , Masculino , Memória de Curto Prazo , Destreza Motora , Testes Neuropsicológicos , Estudos Prospectivos , Desempenho Psicomotor , Reino Unido , Escalas de Wechsler
4.
Arch Dis Child Fetal Neonatal Ed ; 105(1): 64-68, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31092676

RESUMO

OBJECTIVE: Apgar scores of zero at 10 min strongly predict mortality and morbidity in infants. However, recent data reported improved outcomes among infants with Apgar scores of zero at 10 min. We aimed to review the mortality rate and neurodevelopmental outcomes of infants with Apgar scores of zero at 10 min in Japan. DESIGN: Observational study. PATIENTS: Twenty-eight of 768 infants registered in the Baby Cooling Registry of Japan between 2012 and 2016, at >34 weeks' gestation, with Apgar scores of zero at 10 min who were treated with therapeutic hypothermia. INTERVENTIONS: We investigated the time of first heartbeat detection in infants with favourable outcomes and who had neurodevelopmental impairments or died. MAIN OUTCOME MEASURES: Clinical characteristics, mortality rate and neurodevelopmental outcomes at 18-22 months of age were evaluated. RESULTS: Nine (32%) of the 28 infants died before 18 months of age; 16 (57%) survived, but with severe disabilities and 3 (11%) survived without moderate-to-severe disabilities. At 20 min after birth, 14 of 27 infants (52%) did not have a first heartbeat, 13 of them died or had severe disabilities and one infant, who had the first heartbeat at 20 min, survived without disability. CONCLUSION: Our study adds to the recent evidence that neurodevelopmental outcomes among infants with Apgar scores of zero at 10 min may not be uniformly poor. However, in our study, all infants with their first heartbeat after 20 min of age died or had severe disabilities.


Assuntos
Índice de Apgar , Asfixia Neonatal/mortalidade , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/mortalidade , Transtornos do Neurodesenvolvimento/epidemiologia , Asfixia Neonatal/terapia , Reanimação Cardiopulmonar , Seguimentos , Gastrostomia/estatística & dados numéricos , Humanos , Hipóxia-Isquemia Encefálica/terapia , Lactente , Recém-Nascido , Intubação Intratraqueal , Japão/epidemiologia , Testes Neuropsicológicos , Sistema de Registros , Respiração Artificial/estatística & dados numéricos , Traqueostomia/estatística & dados numéricos , Escala de Memória de Wechsler
5.
BMJ ; 367: l6459, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31818811

RESUMO

General anesthesia has been unequivocally linked to abnormal development of the central nervous system, leading to neurocognitive impairments in laboratory models. In vitro and in vivo studies have consistently shown that exposure to GABA agonists (eg, volatile anesthetics, midazolam, and propofol) or NMDA antagonists (eg, ketamine, isoflurane, and nitrous oxide) produces dose dependent and developmental age dependent effects on various neuronal transmission systems. Exposure to these drugs increases neuronal cell death in juvenile animals including rats, mice, and non-human primates. The possibility of anesthetic induced neurotoxicity occurring in children has led to concerns about the safety of pediatric anesthesia. A spectrum of behavioral changes has been documented after general anesthetic exposure in young children, including emergence delirium, which may be evidence of toxicity. Most clinical studies are retrospective; specifics about medications or monitoring are unavailable and many of the outcomes may not be sensitive to detect small neurocognitive deficits. Some of these retrospective studies have shown an association between anesthesia exposure at a young age and neurocognitive deficits, but others have not. Practitioners and families should be reassured that although general anesthetics have the potential to induce neurotoxicity, very little clinical evidence exists to support this.


Assuntos
Anestesia Geral/efeitos adversos , Anestésicos/farmacologia , Sistema Nervoso Central , Transtornos do Neurodesenvolvimento/induzido quimicamente , Síndromes Neurotóxicas/etiologia , Animais , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/crescimento & desenvolvimento , Criança , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Humanos , Lactente , Fatores de Risco
6.
Medicine (Baltimore) ; 98(50): e18229, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852083

RESUMO

BACKGROUND: The relationships between chorioamnionitis (CA) and neurodevelopmental outcomes in preterm infants remain controversial. The meta-analysis aims to evaluate the associations between CA and neurodevelopmental deficits in preterm infants. METHODS: All studies exploring the associations between CA and neurodevelopmental deficits in preterm infants were retrieved from the following databases: PubMed, Embase, OVID, EBSCO, ProQuest, CDSR, and CENTRAL. The NOS was used to evaluate the quality of the studies, RevMan was adopted to analyze the data. RESULTS: Twelve studies involving 4267 preterm infants were included. The ORs across studies was 0.95 (P = .77, I = 51%) for cognitive deficits, 1.09 (P = .44, I = 10%) for psychomotor deficits, 1.21 (P = .08, I = 25%) for language deficits, 2.34 (P = .02, I = 0%) for performance intelligence quotient impairment and 2.81 (P = .03, I = 0%) for verbal intelligence quotient impairment. Subgroup analyses based on the severity of cognitive deficits indicated that CA might be correlated with severe cognitive deficits (P = .01, I = 0%) but not with mild cognitive deficits (P = .40, I = 19%). In terms of the CA category, clinical CA may be related to overall psychomotor deficits (P = .01, I = 25%) and overall language deficits (P < .00001, I = 23%) other than histological CA. CONCLUSION: In preterm infants, CA might be a risk factor for performance and verbal intelligence quotient impairment and severe cognitive deficits, and clinical CA might be a risk factor for overall psychomotor and language deficits.


Assuntos
Corioamnionite/epidemiologia , Doenças do Prematuro/etiologia , Recém-Nascido Prematuro , Transtornos do Neurodesenvolvimento/etiologia , Feminino , Saúde Global , Humanos , Incidência , Recém-Nascido , Doenças do Prematuro/epidemiologia , Transtornos do Neurodesenvolvimento/epidemiologia , Gravidez , Fatores de Risco
7.
Medicine (Baltimore) ; 98(44): e17689, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689792

RESUMO

The article presents findings from the validation of the Polish version of the Short Sensory Profile, 2nd edition (SSP-2-PL).A total of 1230 participants were recruited: 310 diagnosed with autism spectrum disorder (ASD), 264 with nonspectrum neurodevelopmental disorders, and 656 typically developing (TD). The reliability and validity of the questionnaire were estimated using several methods, including internal consistency, test-retest, and factor analysis.Exploratory factor analysis identified a unidimensional solution in both the TD and ASD groups. The structure of SSP-2 seems to be homogeneous; therefore, the findings support the validity of calculating the SSP-2 overall score. Cronbach alphas and intraclass correlation coefficients exceeded 0.90 for overall total in all study groups. The Social Communication Questionnaire total score correlated moderately with SSP-2 scores. A 1-way analysis of variance yielded statistically significant differences at P < .001 between groups on all scales/quadrants and the overall score. Our results indicate greater severity of sensory processing problems among children with ASD and non-ASD disorders than among TD peers. Among children with ASD, 85% experienced problems with sensory processing. Scores in SSP-2-PL were not affected by the children's age, gender, informant, and informant's level of education.To the best of our knowledge, this is the 1st study on non-English participants using a revised version of the SSP-2. The results confirm the prevalence of sensory processing problems among children with neurodevelopmental disorders, especially with ASD. SSP-2-PL has high reliability in terms of both internal consistency and stability of scores. The results suggest that SSP-2 overall score could be used for screening purposes, namely to identify sensory processing and behavioral problems combined into one factor. Further analyzes of the SSP-2 factor structure are needed to confirm the findings of the present study.


Assuntos
Transtorno do Espectro Autista/fisiopatologia , Inquéritos e Questionários/normas , Adolescente , Criança , Pré-Escolar , Análise Fatorial , Feminino , Humanos , Masculino , Transtornos do Neurodesenvolvimento/fisiopatologia , Polônia , Psicometria , Reprodutibilidade dos Testes , Tradução
8.
Nat Commun ; 10(1): 4679, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31616000

RESUMO

Postsynaptic density (PSD) proteins have been implicated in the pathophysiology of neurodevelopmental and psychiatric disorders. Here, we present detailed clinical and genetic data for 20 patients with likely gene-disrupting mutations in TANC2-whose protein product interacts with multiple PSD proteins. Pediatric patients with disruptive mutations present with autism, intellectual disability, and delayed language and motor development. In addition to a variable degree of epilepsy and facial dysmorphism, we observe a pattern of more complex psychiatric dysfunction or behavioral problems in adult probands or carrier parents. Although this observation requires replication to establish statistical significance, it also suggests that mutations in this gene are associated with a variety of neuropsychiatric disorders consistent with its postsynaptic function. We find that TANC2 is expressed broadly in the human developing brain, especially in excitatory neurons and glial cells, but shows a more restricted pattern in Drosophila glial cells where its disruption affects behavioral outcomes.


Assuntos
Transtornos Mentais/genética , Proteínas do Tecido Nervoso/metabolismo , Transtornos do Neurodesenvolvimento/genética , Proteínas/genética , Adolescente , Adulto , Animais , Transtorno Autístico/genética , Transtorno Autístico/psicologia , Comportamento Animal , Encéfalo/metabolismo , Criança , Pré-Escolar , Anormalidades Craniofaciais/genética , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/psicologia , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Epilepsia/genética , Feminino , Humanos , Deficiência Intelectual/genética , Deficiência Intelectual/psicologia , Transtornos do Desenvolvimento da Linguagem/genética , Transtornos do Desenvolvimento da Linguagem/psicologia , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Transtornos Mentais/psicologia , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Mutação , Transtornos do Neurodesenvolvimento/psicologia , Neuroglia/metabolismo , Neurônios/metabolismo , Proteínas/metabolismo , Sequenciamento Completo do Exoma , Adulto Jovem
9.
Nat Genet ; 51(11): 1624-1636, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31636452

RESUMO

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.


Assuntos
Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Drosophila melanogaster/metabolismo , Variação Genética , Estudo de Associação Genômica Ampla , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/patologia , Adulto , Idoso , Animais , Estudos de Coortes , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Tamanho do Órgão
10.
BMJ Case Rep ; 12(2)2019 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31603075

RESUMO

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is a congenital disorder characterised by macrocephaly, multiple hamartomas, lipomas, and pigmented macules of the glans penis. Intermediate uveitis is characterised by chronic inflammatory cells aggregates on the pars plana (snowbanks) and within the vitreous cavity (snowballs). We describe what we believe to be the first case of intermediate uveitis associated with BRRS. Early examination under anaesthesia should be considered in the management of young children diagnosed with this syndrome in order to provide appropriate ocular evaluation, treatment and follow-up. Further research is needed to establish a better understanding of the ophthalmic manifestations of this syndrome.


Assuntos
Síndrome do Hamartoma Múltiplo/complicações , Transtornos do Neurodesenvolvimento/genética , PTEN Fosfo-Hidrolase/genética , Uveíte Intermediária/etiologia , Criança , Diagnóstico Precoce , Síndrome do Hamartoma Múltiplo/diagnóstico , Síndrome do Hamartoma Múltiplo/genética , Humanos , Masculino , Mutação/genética , Transtornos do Neurodesenvolvimento/etiologia , PTEN Fosfo-Hidrolase/metabolismo , Uveíte Intermediária/diagnóstico , Uveíte Intermediária/patologia
11.
Nat Commun ; 10(1): 4457, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31575858

RESUMO

Mutations in genes encoding KATP channel subunits have been reported for pancreatic disorders and Cantú syndrome. Here, we report a syndrome in six patients from two families with a consistent phenotype of mild intellectual disability, similar facies, myopathy, and cerebral white matter hyperintensities, with cardiac systolic dysfunction present in the two oldest patients. Patients are homozygous for a splice-site mutation in ABCC9 (c.1320 + 1 G > A), which encodes the sulfonylurea receptor 2 (SUR2) subunit of KATP channels. This mutation results in an in-frame deletion of exon 8, which results in non-functional KATP channels in recombinant assays. SUR2 loss-of-function causes fatigability and cardiac dysfunction in mice, and reduced activity, cardiac dysfunction and ventricular enlargement in zebrafish. We term this channelopathy resulting from loss-of-function of SUR2-containing KATP channels ABCC9-related Intellectual disability Myopathy Syndrome (AIMS). The phenotype differs from Cantú syndrome, which is caused by gain-of-function ABCC9 mutations, reflecting the opposing consequences of KATP loss- versus gain-of-function.


Assuntos
Trifosfato de Adenosina/metabolismo , Canalopatias/metabolismo , Predisposição Genética para Doença/genética , Deficiência Intelectual/metabolismo , Doenças Musculares/metabolismo , Mutação , Receptores Sulfonilureia/genética , Receptores Sulfonilureia/metabolismo , Adolescente , Adulto , Sequência de Aminoácidos , Animais , Cardiomegalia/genética , Cardiomegalia/metabolismo , Linhagem Celular , Criança , Modelos Animais de Doenças , Facies , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/genética , Coração , Cardiopatias/genética , Cardiopatias/metabolismo , Homozigoto , Humanos , Hipertricose/genética , Hipertricose/metabolismo , Deficiência Intelectual/parasitologia , Masculino , Complexo Mediador/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Doenças Musculares/genética , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/metabolismo , Transtornos do Neurodesenvolvimento/fisiopatologia , Osteocondrodisplasias/genética , Osteocondrodisplasias/metabolismo , Linhagem , Fenótipo , Rubídio , Sequenciamento Completo do Genoma , Adulto Jovem , Peixe-Zebra
13.
Hum Genet ; 138(11-12): 1259-1266, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31555905

RESUMO

Alkylglycerol monooxygenase (AGMO) is the only enzyme known to cleave the O-alkyl bonds of ether lipids (alkylglycerols) which are essential components of cell membranes. A homozygous frameshift variant [p.(Glu324LysfsTer12)] in AGMO has recently been reported in two male siblings with syndromic microcephaly. In this study, we identified rare nonsense, in frame deletion, and missense biallelic variants in AGMO in two unrelated individuals with neurodevelopmental disabilities. We assessed the activity of seven disease associated AGMO variants including the four variants identified in our two affected individuals expressed in human embryonic kidney (HEK293T) cells. We demonstrated significantly diminished enzyme activity for all disease-associated variants, supporting the mechanism as decreased AGMO activity. Future mechanistic studies are necessary to understand how decreased AGMO activity leads to the neurologic manifestations.


Assuntos
Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Mutação , Transtornos do Neurodesenvolvimento/patologia , Alelos , Células HEK293 , Humanos , Masculino , Transtornos do Neurodesenvolvimento/enzimologia , Transtornos do Neurodesenvolvimento/genética , Prognóstico
14.
Pediatrics ; 144(4)2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31515298

RESUMO

OBJECTIVES: To examine screening practices for autism spectrum disorder (ASD), subsequent referrals, and diagnostic outcomes within a large network of primary pediatric care practices. METHODS: Rates of ASD screening with the Modified Checklist for Autism in Toddlers (M-CHAT) at 18- and 24-month well-child visits were examined among 290 primary care providers within 54 pediatric practices between June 2014 and June 2016. Demographic, referral, and diagnostic data were abstracted from the medical records for all children who failed the M-CHAT (ie, score of ≥3) at either or both visits. RESULTS: Rates of M-CHAT screening were 93% at 18 months and 82% at 24 months. Among 23 514 screens, scores of 648 (3%) were ≥3 (386 at 18 months, 262 at 24 months) among 530 unique children who failed 1 or both screenings. Among screen-failed cases, 18% received a diagnosis of ASD and 59% received ≥1 non-ASD neurodevelopmental disorder diagnosis within the follow-up period. Only 31% of children were referred to a specialist for additional evaluation. CONCLUSIONS: High rates of ASD-specific screening do not necessarily translate to increases in subsequent referrals for ASD evaluation or ASD diagnoses. Low rates of referrals and/or lack of follow-through on referrals appear to contribute to delays in children's receipt of ASD diagnoses. Additional education of primary care providers regarding the referral process after a failed ASD screening is warranted.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Lista de Checagem , Pediatria/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos , Fatores Etários , Transtorno do Espectro Autista/epidemiologia , Pré-Escolar , Humanos , Lactente , Perda de Seguimento , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/epidemiologia
15.
Pediatrics ; 144(4)2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31548334

RESUMO

Pediatricians and other pediatric primary care providers may be consulted when families have concerns that their child is not making expected progress in school. Pediatricians care not only for an increasingly diverse population of children who may have behavioral, psychological, and learning difficulties but also for increasing numbers of children with complex and chronic medical problems that can affect the development of the central nervous system and can present with learning and academic concerns. In many instances, pediatric providers require additional information about the nature of cognitive, psychosocial, and educational difficulties that affect their school-aged patients. Our purpose for this report is to describe the current state of the science regarding educational achievement to inform pediatricians' decisions regarding further evaluation of a child's challenges. In this report, we review commonly available options for psychological evaluation and/or treatment, medical referrals, and/or recommendations for referral for eligibility determinations at school and review strategies for collaborating with families, schools, and specialists to best serve children and families.


Assuntos
Desempenho Acadêmico , Pediatras , Papel do Médico , Criança , Defesa da Criança e do Adolescente , Diagnóstico Diferencial , Diagnóstico Precoce , Educação Especial/legislação & jurisprudência , Humanos , /prevenção & controle , Anamnese , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/terapia , Privacidade/legislação & jurisprudência , Encaminhamento e Consulta , Fatores de Tempo
16.
BJOG ; 126(13): 1588-1597, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31529591

RESUMO

OBJECTIVE: To examine the association of prenatal alcohol exposure (PAE) on cognitive abilities and behaviour profiles of 4-year-old children. DESIGN: Prospective cohort study. SETTING: Cape Town, South Africa. POPULATION: A cohort of 500 children. METHODS: Children from the Safe Passage Study, which prospectively collected PAE, were included. Cognition and behavioural profiles were assessed. Children with and without PAE were compared. Mean scores were compared, with P ≤ 0.05 considered significant. Results were adjusted for confounding factors. MAIN OUTCOME MEASURES: The Kaufman Assessment Battery for children measured intellectual and mental ability; the NEPSY-II instrument assessed neurocognitive performance. The caregiver completed the Preschool Child Behaviour checklist to rate the child's problem behaviours and competencies. RESULTS: Two hundred children had no PAE, 117 children had mild to moderate PAE (with no binge episodes), 113 children had heavy PAE (with one or two binge episodes), and 70 children had very heavy PAE (with three or more binge episodes). Women who binge drank had significantly higher rates of smoking, marijuana use, and methamphetamine use. Low to moderate PAE had no effect on cognitive ability and behaviour. Very heavy PAE was associated with problems performing simultaneous as well as sequential functions, lower scores in the language and sensorimotor domain, and more attention and pervasive developmental problems. CONCLUSIONS: Low to moderate PAE was not associated with cognitive processing or developmental problems. Women who had many binge drinking episodes during pregnancy were the most at risk for cognitive processing, neurocognitive, and behaviour problems in their children at 4 years of age. TWEETABLE ABSTRACT: Low to moderate prenatal alcohol use was not associated with cognitive or behavioural problems in 4-year-olds.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Desenvolvimento Infantil/fisiologia , Transtornos do Neurodesenvolvimento/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Pré-Escolar , Feminino , Seguimentos , Inquéritos Epidemiológicos , Humanos , Masculino , Transtornos do Neurodesenvolvimento/epidemiologia , Testes Neuropsicológicos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos Prospectivos , África do Sul/epidemiologia
17.
Genes Dev ; 33(19-20): 1381-1396, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31488579

RESUMO

Short telomere syndromes manifest as familial idiopathic pulmonary fibrosis; they are the most common premature aging disorders. We used genome-wide linkage to identify heterozygous loss of function of ZCCHC8, a zinc-knuckle containing protein, as a cause of autosomal dominant pulmonary fibrosis. ZCCHC8 associated with TR and was required for telomerase function. In ZCCHC8 knockout cells and in mutation carriers, genomically extended telomerase RNA (TR) accumulated at the expense of mature TR, consistent with a role for ZCCHC8 in mediating TR 3' end targeting to the nuclear RNA exosome. We generated Zcchc8-null mice and found that heterozygotes, similar to human mutation carriers, had TR insufficiency but an otherwise preserved transcriptome. In contrast, Zcchc8-/- mice developed progressive and fatal neurodevelopmental pathology with features of a ciliopathy. The Zcchc8-/- brain transcriptome was highly dysregulated, showing accumulation and 3' end misprocessing of other low-abundance RNAs, including those encoding cilia components as well as the intronless replication-dependent histones. Our data identify a novel cause of human short telomere syndromes-familial pulmonary fibrosis and uncover nuclear exosome targeting as an essential 3' end maturation mechanism that vertebrate TR shares with replication-dependent histones.


Assuntos
Proteínas de Transporte/genética , Fibrose Pulmonar Idiopática/genética , Mutação com Perda de Função , Proteínas Nucleares/genética , RNA/metabolismo , Telomerase/metabolismo , Animais , Encéfalo/enzimologia , Encéfalo/fisiopatologia , Linhagem Celular , Cílios/genética , Feminino , Ligação Genética , Células HCT116 , Humanos , Fibrose Pulmonar Idiopática/enzimologia , Fibrose Pulmonar Idiopática/fisiopatologia , Masculino , Camundongos , Camundongos Knockout , Transtornos do Neurodesenvolvimento/genética , Linhagem , Processamento Pós-Transcricional do RNA/genética , Encurtamento do Telômero/genética
18.
Psychiatr Danub ; 31(Suppl 3): 455-461, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488772

RESUMO

Complex disability is very difficult to manage. It usually subtends very serious clinical pictures, because it affect several body systems, or because it is associated with intellectual disability and behavioral disorders. Often affected patients are unable to communicate their basic needs. All these factors combine to make the management of these patients very complex, and those who care for them realize how important it is to find a way to detect their state and to identify their potential capabilities. Developing appropriate rehabilitation programs for these patients requires additional effort and an assessment capacity that is as objective as possible. Few scales cited in the literature are capable of evaluating these aspects in patients with complex disabilities, among them the Barthel Index (Mahoney & Barthel 1965) and the Vineland Adaptive Behavior scale II (Sparrow et al. 2005). The majority of these scales often tend to depict the data regarding the disease to a degree of severity that precludes adequate individual rehabilitation program development. There is a dire need for a more appropriate instrument, an observational grid that is capable of identifying the potential of this patient population and evaluate the effectiveness of rehabilitation interventions provided. The aim of the study is to evaluate the efficacy of rehabilitation interventions in a group of patients with IQ <32 (determined by the Vineland II scale) using an evaluation tool created ad hoc called D-Rubrics, designed with the intent to identify "micro-differences" between baseline (T0) and post-rehabilitation (T1). The goal is part of a more long term-term objective which involves developing an effective assessment tool for patients with complex disabilities. Such an assessment tool should be practical, easy to administer and useful in both clinical and research settings.


Assuntos
Transtornos do Neurodesenvolvimento/reabilitação , Reabilitação/normas , Humanos , Deficiência Intelectual/complicações , Deficiência Intelectual/reabilitação , Transtornos do Neurodesenvolvimento/complicações
19.
Adv Exp Med Biol ; 1178: 77-101, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31493223

RESUMO

This chapter reviews the efficacy of the ketogenic diet in a variety of neurodegenerative, neurodevelopmental and metabolic conditions throughout different stages of life. It describes conditions affecting children, metabolic disorders in adults and disorderrs affecting the elderly. We have focused on application of the ketogenic diet in clinical studies and in preclinical models and discuss the benefits and negative aspects of the diet. Finally, we highlight the need for further research in this area with a view of discovering novel mechanistic targets of the ketogenic diet, as a means of maximising the potential benefits/risks ratio.


Assuntos
Dieta Cetogênica , Doenças Metabólicas , Doenças Neurodegenerativas , Transtornos do Neurodesenvolvimento , Humanos , Doenças Metabólicas/dietoterapia , Doenças Neurodegenerativas/dietoterapia , Transtornos do Neurodesenvolvimento/dietoterapia
20.
Complement Ther Clin Pract ; 36: 153-157, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31383432

RESUMO

Animal-assisted activities (AAA), a form of animal-assisted interaction, have the potential to improve positive coping for youth with significant psychiatric symptoms admitted to acute behavioral health units. However, little is known regarding the appropriateness of an AAA program in short-term mental health hospital settings. The goal of this investigation is to describe and report on the feasibility and acceptability of embedding a canine-AAA program within the therapeutic programming of a pediatric behavioral health unit. Both patient participants and unit staff completed quantitative and qualitative measures. Outcomes yielded preliminary data suggesting AAA was feasible and acceptable to patients and unit staff. Initial efficacy outcomes demonstrated decreases in subjective distress. Qualitative data provided areas for further refinement of the AAA program.


Assuntos
Terapia Assistida por Animais , Hospitalização , Transtornos do Neurodesenvolvimento/terapia , Animais , Criança , Cães , Estudos de Viabilidade , Humanos
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