Principles and Practices of Neurodevelopmental Assessment in Children: Lessons Learned from the Centers for Children’s Environmental Health and Disease Prevention Research

Principles and practices of pediatric neurotoxicology are reviewed here with the purpose of guiding the design and execution of the planned National Children’s Study. The developing human central nervous system is the target organ most vulnerable to environmental chemicals. An investigation of the effects of environmental exposures on child development is a complex endeavor that requires consideration of numerous critical factors pertinent to a study’s concept, design, and execution. These include the timing of neurodevelopmental assessment, matters of biologic plausibility, site, child and population factors, data quality assurance and control, the selection of appropriate domains and measures of neurobehavior, and data safety and monitoring. Here we summarize instruments for the assessment of the neonate, infant, and child that are being employed in the Centers for Children’s Environmental Health and Disease Prevention Research, sponsored by the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency, discuss neural and neurobiologic measures of development, and consider the promises of gene–environment studies. The vulnerability of the human central nervous system to environmental chemicals has been well established, but the contribution these exposures may make to problems such as attention deficit disorder, conduct problems, pervasive developmental disorder, or autism spectrum disorder remain uncertain. Large-scale studies such as the National Children’s Study may provide some important clues. The human neurodevelopmental phenotype will be most clearly represented in models that include environmental chemical exposures, the social milieu, and complex human genetic characteristics that we are just beginning to understand

Knowledge and practices regarding child development among primary healthcare professionals

OBJECTIVE: To evaluate the knowledge and practices regarding child development among physicians working in primary healthcare units. METHOD: Cross-sectional descriptive study carried out at primary healthcare units in Embu, São Paulo, Brazil. Study procedures: 1) Evaluation of knowledge: test consisting of 20 multiple-choice questions on child development applied to all 31 physicians who were providing pediatric care at the primary healthcare units; 2) Evaluation of practices: semi-structured interview applied to a sample of 154 mothers/caregivers of children aged up to 36 months during follow-up visits at primary healthcare units in the municipality. For the comparisons of categorical variables (evaluation/advices about development in visits of children at different ages), the chi-square test was employed. RESULTS: The mean number of correct responses among physicians was 14.8. The error rate for seven questions was greater than 30% (sensory development, language acquisition, physiology of the nervous system, clinical and laboratory diagnosis of congenital infections and innate errors of metabolism) and the rate of correct responses was greater than 85% for four questions (motor and personal-social development markers, risk factors and genetic syndromes). Regarding practices, in 69 (45%) visits, the doctor asked the mother/caregiver's opinion about the child's development; in 80 (52%), the mother/caregiver said that the doctor assessed the development; and in 64 (42%), the mother/caregiver said that the doctor advised them on practices for child's stimulation. CONCLUSIONS: Faulty knowledge and practices regarding child development were identified among primary care professionals, indicating the need for continued education.OBJETIVO: Avaliar o conhecimento e as práticas sobre desenvolvimento infantil de médicos que atuam em Unidades Básicas de Saúde (UBS). MÉTODO: Estudo transversal, descritivo, realizado nas UBS de Embu (SP). Procedimentos do estudo: 1) avaliação do conhecimento por teste contendo 20 questões de múltipla escolha sobre desenvolvimento da criança aplicado a 31 médicos (universo) que prestam assistência pediátrica em UBS; 2) avaliação das práticas - entrevista semiestruturada aplicada para uma amostra de 154 mães/cuidadores que acompanhavam crianças com idade menor ou igual a 36 meses em consulta médica agendada em UBS do município. Para comparação de variáveis categóricas (avaliação/orientações sobre desenvolvimento em consultas de crianças de diferentes faixas etárias), utizou-se o qui-quadrado. RESULTADOS: A média de acertos dos médicos foi de 14,8 questões; sete questões apresentaram índices de erros superiores a 30% (desenvolvimento sensorial, aquisição de linguagem, fisiologia do sistema nervoso, diagnóstico clínico e laboratorial de infecções congênitas, erros inatos do metabolismo) e quatro questões apresentaram acertos acima de 85% (marcos do desenvolvimento motor, pessoal-social, fatores de risco e síndrome genética). Quanto às práticas, em 69 (45%) consultas o médico perguntou a opinião da mãe/cuidador sobre o desenvolvimento da criança, em 80 (52%) a mãe/cuidador referiu que o médico fez alguma pergunta e/ou avaliou o desenvolvimento e em 64 (42%) orientou sobre como estimular a criança. CONCLUSÕES: Identificaram-se falhas de conhecimento e nas práticas dos profissionais referentes ao desenvolvimento da criança, o que indica a necessidade de implementar educação permanente.UNIFESP Curso de MedicinaUNIFESP Projeto DesenvolverSecretaria Municipal de Saúde do EmbuUNIFESP Departamento de Pediatria Disciplina de Pediatria Geral e ComunitáriaUNIFESP, Curso de MedicinaUNIFESP, Projeto DesenvolverUNIFESP, Depto. de Pediatria Disciplina de Pediatria Geral e ComunitáriaSciEL

Fractional anisotropy in white matter tracts of very-low-birth-weight infants

Background: Advances in neonatal intensive care have not yet reduced the high incidence of neurodevelopmental disability among very-low-birth-weight (VLBW) infants. As neurological deficits are related to white-matter injury, early detection is important. Diffusion tensor imaging (DTI) could be an excellent tool for assessment of white-matter injury. Objective: To provide DTI fractional anisotropy (FA) reference values for white-matter tracts of VLBW infants for clinical use. Materials and methods: We retrospectively analysed DTI images of 28 VLBW infants (26-32 weeks gestational age) without evidence of white-matter abnormalities on conventional MRI sequences, and normal developmental outcome (assessed at age 1-3 years). For DTI an echoplanar sequence with diffusion gradient (b = 1,000 s/mm2) applied in 25 non-collinear directions was used. We measured FA and apparent diffusion coefficient (ADC) of different white-matter tracts in the first 4 days of life. Results: A statistically significant correlation was found between gestational age and FA of the posterior limb of the internal capsule in VLBW infants (r = 0.495, P<0.01). Conclusion: Values of FA and ADC were measured in white-matter tracts of VLBW infants. FA of the pyramidal tracts measured in the first few days after birth is related to gestational age

Traits Contributing to the Autistic Spectrum

It is increasingly recognised that traits associated with autism reflect a spectrum with no clear boundary between typical and atypical behaviour. Dimensional traits are needed to investigate the broader autism phenotype.Ninety-three individual measures reflecting components of social, communication and repetitive behaviours characterising autistic spectrum disorder (ASD) were identified between the ages of 6 months and 9 years from the ALSPAC database. Using missing value imputation, data for 13,138 children were analysed. Factor analysis suggested the existence of 7 factors explaining 85% of the variance. The factors were labelled: verbal ability, language acquisition, social understanding, semantic-pragmatic skills, repetitive-stereotyped behaviour, articulation and social inhibition. Four factors (1, 3, 5 and 7) were specific to ASD being more strongly associated with this phenotype than other co-morbid conditions while other factors were more associated with learning difficulties and specific language impairment. Nevertheless, all 7 factors contributed independently to the explanation of ASD (p<0.001). Exploration of putative genetic causal factors such as variants in the CNTNAP2 gene showed a varying pattern of associations with these traits. An alternative predictive model of ASD was derived using four individual measures: the coherence subscale of the Children's Communication Checklist (9y), the Social and Communication Disorders Checklist (91 m), repetitive behaviour (69 m) and the sociability subscale of the Emotionality Activity and Sociability measure (38 m). Although univarably these traits performed better than some factors, their combined explanations of ASD were similar (R(2) =  0.48).These results support the fractional nature of ASD with different aetiological origins for these components despite pleiotropic genetic effects being observed. These traits are likely to be useful in the exploration of ASD