Evaluation of genomic factors and early childhood stimulation on intelligence in children from a Brazilian birth cohort: The primary role of independent factors.

BACKGROUND: Childhood cognitive abilities are a predictor of health outcomes and adult income potential. Identifying factors associated with childhood intelligence and their interactions is essential in behavioral research. We assessed the impact of genetic variants and early child stimulation (ECS) on child intelligence and examined their possible interaction as potential modifiers of IQ in a population-based longitudinal study. METHODS: Participants of the 2004 Pelotas Birth Cohort study (N = 4231) underwent intelligent quotient (IQ) by WISC-III assessment at 6 years of age. At 24 and 48-months, mothers answered five ECS marker questions, whose sum was used to create a score. The polygenic score for intelligence (IQ-PGS) was constructed from the GWAS-weighted estimate of cognition. Association was assessed using multiple linear regression models adjusted for maternal, family, and child confounding variables. To explore the possible influence of skin color and ethnoracial classification, the regression models were stratified according to the skin color variable, as a sensitivity analysis. RESULTS: In the adjusted analysis, IQ-PGS (ß = 0.79, 95% confidence interval [95% CI] 0.26;1.31) as well as ECS (ß = 2.34; 95% CI: 1.76;2.92) were associated with IQ in this sample. The association between IQ-PGS and IQ was significant only in the white Brazilian group in the sensitivity analysis. However, there was no interaction between IQ-PGS and ECS on IQ (p(IQ-PGS x ECS) = 0.46). CONCLUSIONS: ECS did not modify the impact of genetic potential on intellectual development during childhood, suggesting that genetic factors and ECS exert independent effects on the IQ levels of children.

The contribution of whole-exome sequencing to intellectual disability diagnosis and knowledge of underlying molecular mechanisms: A systematic review and meta-analysis.

Whole-exome sequencing (WES) is useful for molecular diagnosis, family genetic counseling, and prognosis of intellectual disability (ID). However, ID molecular diagnosis ascertainment based on WES is highly dependent on de novo mutations (DNMs) and variants of uncertain significance (VUS). The quantification of DNM frequency in ID molecular diagnosis ascertainment and the biological mechanisms common to genes with VUS may provide objective information about WES use in ID diagnosis and etiology. We aimed to investigate and estimate the rate of ID molecular diagnostic assessment by WES, quantify the contribution of DNMs to this rate, and biologically and functionally characterize the genes whose mutations were identified through WES. A PubMed/Medline, Web of Science, Scopus, Science Direct, BIREME, and PsycINFO systematic review and meta-analysis was performed, including studies published between 2010 and 2022. Thirty-seven articles with data on ID molecular diagnostic yield using the WES approach were included in the review. WES testing accounted for an overall diagnostic rate of 42% (Confidence interval (CI): 35-50%), while the estimate restricted to DNMs was 11% (CI: 6-18%). Genetic information on mutations and genes was extracted and split into two groups: (1) genes whose mutation was used for positive molecular diagnosis, and (2) genes whose mutation led to uncertain molecular diagnosis. After functional enrichment analysis, in addition to their expected roles in neurodevelopment, genes from the first group were enriched in epigenetic regulatory mechanisms, immune system regulation, and circadian rhythm control. Genes from uncertain diagnosis cases were enriched in the renin angiotensin pathway. Taken together, our results support WES as an important approach to the molecular diagnosis of ID. The results also indicated relevant pathways that may underlie the pathogenesis of ID with the renin-angiotensin pathway being suggested to be a potential pathway underlying the pathogenesis of ID.

Genética em Medicina e Enfermagem: percepções de profissionais de saúde envolvidos com o processo ensino-aprendizagem / Genetics in Medicine and Nursing: perceptions of health professionals involved in teaching and learning process

Resumo: Introdução: A evolução na área da genética motivou entidades de medicina e enfermagem a recomendarem competências específicas aos seus profissionais na área. Assim, professores e preceptores envolvidos no processo ensino-aprendizagem devem apresentar e discutir a genética de forma adequada, assegurando formação qualificada aos estudantes. Objetivo: Este estudo teve como objetivo explorar a percepção de professores e preceptores dos cursos de Medicina e Enfermagem de uma universidade pública brasileira sobre o processo ensino-aprendizagem de genética na graduação. Método: Trata-se de um estudo exploratório, descritivo e transversal, desenvolvido com amostra de conveniência, cuja coleta de dados foi feita por meio de questionário eletrônico autoaplicável. Foram convidados 317 profissionais, dos quais 40 (12,6%) participaram. Fez-se estatística descritiva dos dados, que foram classificados em cinco categorias: 1. descrição, formação acadêmica e atuação profissional da amostra, 2. genética no processo ensino-aprendizagem, 3. educação continuada em genética médica/clínica, 4. genética na prática clínica e 5. testes genéticos. Resultado: Participaram da amostra 28 (70%) médicos, sete (17,5%) enfermeiros e cinco (12,5%) profissionais de outras áreas da saúde, sendo 87,5% mestres ou doutores. Sobre o processo ensino-aprendizagem, 31 (77,5%) participantes relataram que sua atuação se relacionava indiretamente com a genética, embora 29 (72,5%) nunca tenham realizado atividade de educação continuada na área. Na prática clínica, dois (5%) participantes mencionaram que faziam história familiar até a terceira geração, dez (25%) relataram que orientavam as gestantes sobre teratógenos durante a gestação e lactação, e 17 (42,5%) afirmaram que encaminhavam ocasionalmente pacientes ao especialista em genética. Os participantes foram, em geral, capazes de identificar as principais características clínicas que levam à suspeição de doenças genéticas, embora algumas situações tenham sido subestimadas, como a importância do aconselhamento genético nos casos de consanguinidade e idade materna ou paterna avançada. Sobre testes genéticos, apenas cinco (12%) participantes relataram que se sentiam seguros para solicitar, interpretar e comunicar seus resultados. Conclusão: Espera-se que docentes e preceptores de áreas da saúde estimulem seus estudantes a articular teoria e prática, incorporando habilidades e competências relacionadas à genética no cuidado integral dos indivíduos. A partir dos resultados, podem ser identificadas oportunidades para aprimorar o ensino de genética nessa e em outras instituições de ensino superior.

Abstract: Introduction: The evolution of genetics has led to medical and nursing entities recommending specific skills to their health professionals. Professors and preceptors in the area must therefore introduce and discuss genetics accordingly to ensure proper training for students. Objective: This study aimed to explore how professors and preceptors of Medicine and Nursing courses at a Brazilian public university perceive the subject matter of genetics in the teaching and learning process of undergraduate studies. Method: This is a descriptive, exploratory, and cross-sectional study that was conducted with a convenience sample, and data was collected through a self-administered electronic questionnaire. In total, 317 professionals were invited and 40 (12.6%) participated. Descriptive data statistics were developed and classified into five categories: 1. description, academic training, and professional information; 2. genetics in the teaching and learning process; 3. continuing education in medical/clinical genetics; 4. genetics in clinical practice; and 5. genetic testing. Result: Twenty-eight (70%) physicians, seven (17.5%) nurses, and five (12.5%) professionals from other health areas participated in the sample, 87.5% of whom have a postgraduate qualification. As regards the teaching and learning process, 31 (77.5%) participants reported that their work was indirectly related to genetics, although 29 (72.5%) had never carried out a continuing education activity in the area. In clinical practice, two (5.0%) participants investigated family history up to three generations back, ten (25%) participants reported advising pregnant women about teratogens during pregnancy and lactation, and 17 (42.5%) reported occasionally referring patients to a genetics specialist. In general, participants were able to identify the main clinical characteristics that lead to suspected genetic diseases, although some situations were underestimated, such as the importance of genetic counseling in cases of consanguinity and advanced maternal or paternal age. Regarding genetic tests, only five (12%) participants reported feeling confident enough to request, interpret, and communicate results. Conclusion: Professors and preceptors in health areas are expected to encourage students to connect theory and practice, incorporating skills and competencies related to genetics into the comprehensive care of individuals. Based on these results, opportunities may be identified to improve the teaching of genetics in this and other higher education institutions.

Medical care in clinical genetics: an experience of decentralization in southern Brazil.

OBJECTIVE: To describe the population assisted in a genetics outpatient clinic, in a medium-sized town, with respect to diagnosis, type of inheritance, and local impact of genetic care. METHODS: Medical records and genetic consultation forms from 2006 to 2018 were reviewed. The variables analyzed were age, sex, origin, current residence, reason for consultation, professional who requested evaluation, final diagnosis, additional exams and their results. RESULTS: A total of 609 patients were seen, 65.9% aged 0 to 12 years. Genetic syndromes were suspected in 15.1%, and 11% presented developmental delay. Neurogenetic disorders stood out among adults. Mendelian inheritance was more prevalent (17.8%). Requests for genetic consultation have doubled in the last 5 years, with 44.4% due to suspected genetic syndrome. CONCLUSION: Genetic consultations have shown to be an important tool for inpatient care, reducing the waiting time to initiate treatment, attenuating potential associated costs, and guiding the families of patients. Outpatient care provided diagnosis and genetic counseling for users from the city and surrounding region, decreased costs and offered a training environment in medical genetics.

List of priority congenital anomalies for surveillance under the Brazilian Live Birth Information System. / Lista de anomalias congênitas prioritárias para vigilância no âmbito do Sistema de Informações sobre Nascidos Vivos do Brasil.

OBJECTIVE: To define the list of priority congenital anomalies for improving their recording on the Brazilian Live Birth Information System (Sinasc). METHODS: Based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10), international protocols and meetings with specialists, the list of priority anomalies was built considering two main criteria: being diagnosable at birth and having intervention available at different levels. The list was submitted for consideration by the Brazilian Medical Genetics and Genomics Society. RESULTS: The list comprised eight groups of congenital anomalies distributed according to the type of related anomaly, as well as the affected part of the body and its corresponding code in ICD-10 Chapter XVII. CONCLUSION: The list of priority congenital anomalies for notification provides a basis for improving case recording on Sinasc.

List of priority congenital anomalies for surveillance under the Brazilian Information System on Live Births / Lista de anomalías congénitas prioritarias para la vigilancia bajo el Sistema de Información sobre Nacimientos Vivos en Brasil / Lista de anomalias congênitas prioritárias para vigilância no âmbito do Sistema de Informações sobre Nascidos Vivos do Brasil

Objective: To define the list of priority congenital anomalies for improving the registration in the Brazilian Live Birth Information System (Sinasc). Methods: Based on International Classification of Diseases, Tenth Revision (ICD-10), internation protocols and meetings with specialists, the list of priority anomalies was built considering two main criteria: being diagnosable at birth and having intervention available at different levels. The list was submitted for consideration by the Brazilian Society of Medical Genetics and Genomics. Results: The list comprised eight groups of congenital anomalies distributed according to the type of anomaly related, as well as the affect body part, all of which were related to some code of chapter XVII of ICD-10. Conclusion: The list of priority congenital anomalies for notification provides subsidies for improving registration at Sinasc.

Objetivo: Definir a lista de anomalias congênitas prioritárias para o aprimoramento do registro no Sistema de Informações sobre Nascidos Vivos (Sinasc). Métodos: A partir da Décima Revisão da Classificação Estatística Internacional de Doenças e Problemas Relacionados à Saúde (CID-10), protocolos internacionais e reuniões com especialistas, a lista de anomalias prioritárias foi construída considerando-se dois critérios principais: ser diagnosticável ao nascimento; e possuir intervenção disponível em diferentes níveis. A lista foi submetida a apreciação da Sociedade Brasileira de Genética Médica e Genômica. Resultados: Compuseram a lista oito grupos de anomalias distribuídos de acordo com o tipo de anomalia relacionada, bem como a parte do corpo afetada e sua correspondência ao código do capítulo XVII da CID-10. Conclusão: A lista de anomalias congênitas prioritárias para notificação fornece subsídios para o aprimoramento do registro no Sinasc.

Medical care in clinical genetics: an experience of decentralization in southern Brazil / Atendimento em genética clínica: uma experiência de descentralização na região Sul do Brasil

ABSTRACT Objective: To describe the population assisted in a genetics outpatient clinic, in a medium-sized town, with respect to diagnosis, type of inheritance, and local impact of genetic care. Methods: Medical records and genetic consultation forms from 2006 to 2018 were reviewed. The variables analyzed were age, sex, origin, current residence, reason for consultation, professional who requested evaluation, final diagnosis, additional exams and their results. Results: A total of 609 patients were seen, 65.9% aged 0 to 12 years. Genetic syndromes were suspected in 15.1%, and 11% presented developmental delay. Neurogenetic disorders stood out among adults. Mendelian inheritance was more prevalent (17.8%). Requests for genetic consultation have doubled in the last 5 years, with 44.4% due to suspected genetic syndrome. Conclusion: Genetic consultations have shown to be an important tool for inpatient care, reducing the waiting time to initiate treatment, attenuating potential associated costs, and guiding the families of patients. Outpatient care provided diagnosis and genetic counseling for users from the city and surrounding region, decreased costs and offered a training environment in medical genetics.

RESUMO Objetivo: Descrever a população atendida em um ambulatório de genética, em uma cidade de médio porte, em relação a diagnóstico, tipo de herança e impacto local do atendimento. Métodos: Foram revisados os prontuários e formulários do serviço de genética entre 2006 e 2018. As variáveis analisadas foram idade, sexo, procedência e atual residência, motivo de referência/consultoria, profissional que encaminhou, diagnóstico final, exames complementares e seus resultados. Resultados: Foram atendidos 609 pacientes, 65,9% com idade de zero a 12 anos. Houve suspeita de síndromes genéticas em 15,1%, e 11% apresentaram atraso no desenvolvimento. Distúrbios neurogenéticos destacaram-se entre os adultos. A herança mendeliana teve maior frequência (17,8%). As solicitações de consultorias genéticas duplicaram nos últimos 5 anos, sendo 44,4% por "suspeita de síndrome genética". Conclusão: As consultorias genéticas mostraram-se ferramenta importante em nível hospitalar, reduzindo o tempo de espera até a instituição terapêutica, minimizando custos potenciais associados e norteando os familiares. O atendimento ambulatorial ofereceu diagnóstico e aconselhamento genético para usuários da cidade e região, diminuiu custos, além de propiciar um ambiente de ensino em genética médica.

Lista de anomalias congênitas prioritárias para vigilância no âmbito do Sistema de Informações sobre Nascidos Vivos do Brasil / Lista de anomalías congénitas prioritarias para la vigilancia bajo el Sistema de Información sobre Nacidos Vivos en Brasil / List of priority congenital anomalies for surveillance under the Brazilian Live Birth Information System

Objetivo: Definir a lista de anomalias congênitas prioritárias para o aprimoramento do registro no Sistema de Informações sobre Nascidos Vivos (Sinasc). Métodos: A partir da Décima Revisão da Classificação Estatística Internacional de Doenças e Problemas Relacionados à Saúde (CID-10), protocolos internacionais e reuniões com especialistas, a lista de anomalias prioritárias foi construída considerando-se dois critérios principais: ser diagnosticável ao nascimento; e possuir intervenção disponível em diferentes níveis. A lista foi submetida a apreciação da Sociedade Brasileira de Genética Médica e Genômica. Resultados: Compuseram a lista oito grupos de anomalias congênitas distribuídos de acordo com o tipo de anomalia relacionada, bem como a parte do corpo afetada e sua correspondência ao código do capítulo XVII da CID-10. Conclusão: A lista de anomalias congênitas prioritárias para notificação fornece subsídios para o aprimoramento do registro no Sinasc.

Objetivo: Definir la lista de anomalías congénitas prioritarias para perfeccionar el registro en el Sistema de Información de Nacidos Vivos (Sinasc). Métodos: Con base en la Clasificación Internacional de Enfermedades, Décima Revisión (CIE-10), protocolos internacionales y reuniones con especialistas, la lista de anomalías prioritarias se construyó considerando dos criterios principales: ser diagnosticables al nacer y tener intervención disponible en diferentes niveles. La lista fue sometida a la consideración de la Sociedad Brasileña de Genética y Genómica Médica. Resultados: La lista comprendía ocho grupos de anomalías congénitas distribuidos según el tipo de anomalía relacionada, así como la parte del cuerpo afectada, todos ellos relacionados con algún código del capítulo XVII de la CIE-10. Conclusión: La lista de anomalías congénitas prioritarias para notificación proporciona subsidios para mejorar el registro en Sinasc.

Objective: To define the list of priority congenital anomalies for improving their recording on the Brazilian Live Birth Information System (Sinasc). Methods: Based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10), international protocols and meetings with specialists, the list of priority anomalies was built considering two main criteria: being diagnosable at birth and having intervention available at different levels. The list was submitted for consideration by the Brazilian Medical Genetics and Genomics Society. Results: The list comprised eight groups of congenital anomalies distributed according to the type of related anomaly, as well as the affected part of the body and its corresponding code in ICD-10 Chapter XVII. Conclusion: The list of priority congenital anomalies for notification provides a basis for improving case recording on Sinasc.

The D-score: a metric for interpreting the early development of infants and toddlers across global settings.

INTRODUCTION: Early childhood development can be described by an underlying latent construct. Global comparisons of children's development are hindered by the lack of a validated metric that is comparable across cultures and contexts, especially for children under age 3 years. We constructed and validated a new metric, the Developmental Score (D-score), using existing data from 16 longitudinal studies. METHODS: Studies had item-level developmental assessment data for children 0-48 months and longitudinal outcomes at ages >4-18 years, including measures of IQ and receptive vocabulary. Existing data from 11 low-income, middle-income and high-income countries were merged for >36 000 children. Item mapping produced 95 'equate groups' of same-skill items across 12 different assessment instruments. A statistical model was built using the Rasch model with item difficulties constrained to be equal in a subset of equate groups, linking instruments to a common scale, the D-score, a continuous metric with interval-scale properties. D-score-for-age z-scores (DAZ) were evaluated for discriminant, concurrent and predictive validity to outcomes in middle childhood to adolescence. RESULTS: Concurrent validity of DAZ with original instruments was strong (average r=0.71), with few exceptions. In approximately 70% of data rounds collected across studies, DAZ discriminated between children above/below cut-points for low birth weight (<2500 g) and stunting (-2 SD below median height-for-age). DAZ increased significantly with maternal education in 55% of data rounds. Predictive correlations of DAZ with outcomes obtained 2-16 years later were generally between 0.20 and 0.40. Correlations equalled or exceeded those obtained with original instruments despite using an average of 55% fewer items to estimate the D-score. CONCLUSION: The D-score metric enables quantitative comparisons of early childhood development across ages and sets the stage for creating simple, low-cost, global-use instruments to facilitate valid cross-national comparisons of early childhood development.

Congenital anomalies in Rio Grande do Sul State: a time series analysis. / Anomalias congênitas no estado do Rio Grande do Sul: análise de série temporal.

INTRODUCTION: In Rio Grande do Sul Sate (Brazil), the incidence of congenital anomalies ranges from 10 to 15/1,000 live births. Identifying risk factors can change congenital anomalies frequency and neonatal mortality. This paper intends to analyze temporal variation of congenital anomalies in the State of Rio Grande do Sul, from 2005 to 2014, and to identify the factors associated with its occurrence. METHOD: This is a descriptive, time series study based on secondary data on congenital anomalies and sociodemographic and health variables of mothers and newborns living in Rio Grande do Sul, from 2005 to 2014. RESULTS: In the period surveyed, there were 1,386,803 births of mothers living in Rio Grande do Sul, and the cases diagnosed with congenital anomalies corresponded to a general average rate of 9.2 per thousand cases, with a greater rate in the group of mothers of newborns whose Apgar score was lower than seven; who had a weight equal to or lower than 1,500 grams; with a gestational age equal to or lower than 31 weeks and living in the metropolitan region. The most frequent types of congenital anomalies were those located in the musculoskeletal system, the nervous system and the circulatory system. CONCLUSION: These data warn us about the change in the epidemiological profile of mothers of children with congenital anomalies, thereby indicating the groups at greatest risk.

INTRODUÇÃO: No estado do Rio Grande do Sul, a incidência de anomalias congênitas varia de 10 a 15/1.000 recém-nascidos vivos. Reconhecer os fatores de risco pode modificar a frequência das anomalias congênitas e a mortalidade neonatal. Este artigo teve o objetivo de analisar a variação temporal de anomalias congênitas no Rio Grande do Sul, de 2005 a 2014, e identificar os fatores associados à sua ocorrência. MÉTODO: Trata-se de um estudo descritivo de série temporal, baseado em dados secundários, sobre anomalias congênitas e as variáveis sociodemográficas e de saúde das mães e dos recém-nascidos residentes no Rio Grande do Sul, no período de 2005 a 2014. RESULTADOS: No período investigado, ocorreram 1.386.803 nascimentos oriundos de mães residentes no Rio Grande do Sul, e os casos diagnosticados com anomalias congênitas corresponderam a uma taxa média geral de 9,2 por mil casos, com maior taxa no grupo de mães de recém-nascidos cujo índice de Apgar foi menor que 7; com peso igual ou menor que 1.500 g; com idade gestacional igual ou menor que 31 semanas e residentes na região metropolitana. As anomalias congênitas mais frequentes foram as do sistema osteomuscular, sistema nervoso e aparelho circulatório. CONCLUSÃO: Esses dados alertam sobre a mudança no perfil epidemiológico das mães de crianças com anomalias congênitas, mostrando os grupos de maior risco.

Anomalias congênitas no estado do Rio Grande do Sul: análise de série temporal / Congenital anomalies in Rio Grande do Sul State: a time series analysis

RESUMO: Introdução: No estado do Rio Grande do Sul, a incidência de anomalias congênitas varia de 10 a 15/1.000 recém-nascidos vivos. Reconhecer os fatores de risco pode modificar a frequência das anomalias congênitas e a mortalidade neonatal. Este artigo teve o objetivo de analisar a variação temporal de anomalias congênitas no Rio Grande do Sul, de 2005 a 2014, e identificar os fatores associados à sua ocorrência. Método: Trata-se de um estudo descritivo de série temporal, baseado em dados secundários, sobre anomalias congênitas e as variáveis sociodemográficas e de saúde das mães e dos recém-nascidos residentes no Rio Grande do Sul, no período de 2005 a 2014. Resultados: No período investigado, ocorreram 1.386.803 nascimentos oriundos de mães residentes no Rio Grande do Sul, e os casos diagnosticados com anomalias congênitas corresponderam a uma taxa média geral de 9,2 por mil casos, com maior taxa no grupo de mães de recém-nascidos cujo índice de Apgar foi menor que 7; com peso igual ou menor que 1.500 g; com idade gestacional igual ou menor que 31 semanas e residentes na região metropolitana. As anomalias congênitas mais frequentes foram as do sistema osteomuscular, sistema nervoso e aparelho circulatório. Conclusão: Esses dados alertam sobre a mudança no perfil epidemiológico das mães de crianças com anomalias congênitas, mostrando os grupos de maior risco.

ABSTRACT: Introduction: In Rio Grande do Sul Sate (Brazil), the incidence of congenital anomalies ranges from 10 to 15/1,000 live births. Identifying risk factors can change congenital anomalies frequency and neonatal mortality. This paper intends to analyze temporal variation of congenital anomalies in the State of Rio Grande do Sul, from 2005 to 2014, and to identify the factors associated with its occurrence. Method: This is a descriptive, time series study based on secondary data on congenital anomalies and sociodemographic and health variables of mothers and newborns living in Rio Grande do Sul, from 2005 to 2014. Results: In the period surveyed, there were 1,386,803 births of mothers living in Rio Grande do Sul, and the cases diagnosed with congenital anomalies corresponded to a general average rate of 9.2 per thousand cases, with a greater rate in the group of mothers of newborns whose Apgar score was lower than seven; who had a weight equal to or lower than 1,500 grams; with a gestational age equal to or lower than 31 weeks and living in the metropolitan region. The most frequent types of congenital anomalies were those located in the musculoskeletal system, the nervous system and the circulatory system. Conclusion: These data warn us about the change in the epidemiological profile of mothers of children with congenital anomalies, thereby indicating the groups at greatest risk.

Prevalence and Severity of Sleep Disturbances among Patients with Early Breast Cancer.

CONTEXT: Data regarding health-related quality of life in breast cancer patients in the Middle East are limited with fatigue and sleep disturbance being the most distressing symptoms reported by patients treated for early breast cancer. AIMS: The aim of this study was to examine the prevalence and incidence of insomnia among patients with early-stage breast cancer patients treated with chemotherapy. SUBJECTS AND METHODS: This was a prospective cohort study. We enrolled patients with stage I-III breast cancer patients treated with chemotherapy at the American University of Beirut Medical Center. At three different time points (prior to, during, and following chemotherapy), we assessed the severity of sleep disturbances using the Pittsburgh Sleep Quality Index and the Insomnia Severity Index. The Institution Review Board approved the study. RESULTS: Fifty-two patients were recruited. There was a significant increase in sleep disturbances during chemotherapy which improved to below baseline levels on completion of therapy. Prior to chemotherapy, 36% of patients reported poor sleep versus 58% during chemotherapy. The percentage of patients reporting clinical insomnia rose from 11% pretreatment to 36% during chemotherapy reflecting a significant symptomatic burden that is poorly documented and managed in routine clinical practice. CONCLUSIONS: Patients with nonmetastatic breast cancer experience an increase in sleep disturbances during the treatment phase. Physicians should be aware of the need to routinely screen for sleep disturbance in breast cancer patients undergoing chemotherapy.

Effect of childhood nutrition counselling on intelligence in adolescence: a 15-year follow-up of a cluster-randomised trial.

OBJECTIVE: The present study aimed to assess the effects of an early childhood nutrition counselling intervention on intelligence (as measured by the intelligence quotient (IQ)) at age 15-16 years. DESIGN: A single-blind, cluster-randomised trial. SETTING: In 1998, in Southern Brazil, mothers of children aged 18 months or younger were enrolled in a nutrition counselling intervention (n 424). Counselling included encouragement and promotion of exclusive breast-feeding until 6 months of age and continued breast-feeding supplemented by protein-, lipid- and carbohydrate-rich foods after age 6 months up to age 2 years. The control group received routine feeding advice. In 2013, the fourth round of follow-up of these individuals, at the age of 15-16 years, was undertaken. IQ was assessed using the short form of the Wechsler Adult Intelligence Scale (WAIS-III). Mental disorders (evaluated using the Development and Well-Being Assessment (DAWBA)) and self-reported school failure, smoking and alcohol use were also investigated. Adjusted analyses were conducted using a multilevel model in accordance with the sampling process. SUBJECTS: Adolescents, mean (sd) age of 15·4 (0·5) years (n 339). RESULTS: Mean (sd) total IQ score was lower in the intervention group than the control group (93·4 (11·4) and 95·8 (11·2), respectively) but the association did not persist after adjustment. The prevalence of any mental disorders was similar between intervention and control groups (23·1 and 23·5 %, respectively). There were no differences between groups regarding school failure, smoking and alcohol use. CONCLUSIONS: Nutrition counselling intervention in early childhood had no effect on intelligence measured during adolescence.

Intellectual Disability in a Birth Cohort: Prevalence, Etiology, and Determinants at the Age of 4 Years.

BACKGROUND: Intellectual disability (ID), characterized by impairments in intellectual function and adaptive behavior, affects 1-3% of the population. Many studies investigated its etiology, but few are cohort studies in middle-income countries. AIMS: To estimate prevalence, etiology, and factors related to ID among children prospectively followed since birth in a Southern Brazilian city (Pelotas). METHODS: In 2004, maternity hospitals were visited daily and births were identified. Live-born infants (n = 4,231) whose family lived in the urban area have been followed for several years. At the age of 2 and 4 years, performances in development and intelligence tests were evaluated using the Battelle Developmental Inventory and Wechsler Intelligence Scale, respectively. Children considered as having developmental delay were invited to attend a genetic evaluation. RESULTS: At 4 years of age, the prevalence of ID was 4.5%, and the etiology was classified into 5 groups: environmental (44.4%), genetic (20.5%), idiopathic (12.6%), neonatal sequelae (13.2%), other diseases (9.3%). Most children presented impairment in two or more areas of adaptive behavior. There was no difference in prenatal care attendance or maternal schooling among the groups. CONCLUSION: For about 40% of children, ID was attributed to nonbiological factors, suggesting that the rate may be reduced with appropriate interventions early in life.

Genetic causes of intellectual disability in a birth cohort: a population-based study.

Intellectual disability affects approximately 1-3% of the population and can be caused by genetic and environmental factors. Although many studies have investigated the etiology of intellectual disability in different populations, few studies have been performed in middle-income countries. The present study estimated the prevalence of genetic causes related to intellectual disability in a cohort of children from a city in south Brazil who were followed from birth. Children who showed poor performance in development and intelligence tests at the ages of 2 and 4 were included. Out of 4,231 liveborns enrolled in the cohort, 214 children fulfilled the inclusion criteria. A diagnosis was established in approximately 90% of the children evaluated. Genetic causes were determined in 31 of the children and 19 cases remained unexplained even after extensive investigation. The overall prevalence of intellectual disability in this cohort due to genetic causes was 0.82%. Because this study was nested in a cohort, there were a large number of variables related to early childhood and the likelihood of information bias was minimized by collecting information with a short recall time. This study was not influenced by selection bias, allowing identification of intellectual disability and estimation of the prevalence of genetic causes in this population, thereby increasing the possibility of providing appropriate management and/or genetic counseling.

Triagem neonatal para hiperfenilalaninemia: um estudo de coorte / Newborn screening for hyperphenylalaninemia: a cohort study

Introdução: A Fenilcetonúria Clássica é causada pela deficiência da enzima hepática fenilalaninahidroxilase. Se não diagnosticada e tratada precocemente, causa retardo mental. O objetivo deste estudo foi identificar indivíduos submetidos à triagem neonatal no Rio Grande do Sul entre 1986 e 2003, com teste positivo para hiperfenilalaninemia, estimar a prevalência de hiperfenilalaninemias, verificar níveis de controle e correlacionar os anos de realização do teste, início do tratamento, evolução e quadro clínico. Métodos: Casos de hiperfenilalaninemia foram identificados nos laboratórios e clínicas de tratamento. Foi aplicado questionário, contendo variáveis demográficas e sobre a patologia, o desenvolvimento infantil, a escolaridade, o aconselhamento genético e o rastreamento neonatal. Foram avaliados pacientes entre 6 meses e 16 anos de idade. Na análise estatística, utilizou-se o teste do qui-quadrado e ANOVA para avaliar a associação entre ano do diagnóstico e controle de fenilalanina e regressão logística para avaliar o efeito conjunto de idade do diagnóstico e controle de fenilalanina sobre o atraso no desenvolvimento. Resultados: De 1986 a 2003, 418 crianças apresentaram teste positivo para fenilalanina. Destes, 351 (84,0%) apresentaram resultados normais na segunda amostra, 58 (13,9%) foram considerados portadores de hiperfenilalaninemia e 9 (2,1%) tiveram o seguimento perdido. A cobertura do programa foi de 50%. Sobre o aconselhamento genético, 39 entrevistados (72,2%) responderam não saber, não lembrar ou deram respostas incorretas. Conclusão: Não se observou tendência histórica do diagnóstico ter se tornado mais precoce ou do controle laboratorial ter se tornado melhor. O controle bioquímico da fenilalanina não dependeu da precocidade do diagnóstico e sim, da idade dos pacientes.

Introduction: Classical phenylketonuria is caused by deficiency of the hepatic enzyme phenylalanine hydroxylase. If not diagnosed and treated early, it causes mental retardation. The aim of this study was to identify patients who underwent neonatal screening in Rio Grande do Sul between 1986 and 2003 and tested positive for hyperphenylalaninemia, to estimate the prevalence of hyperphenyl-alaninaemias, to check the levels of control, and to correlate the years of testing, initiation of treatment, evolution and clinical picture. Methods: Cases of hyperphenylalaninemia were identified in laboratories and treatment clinics. A questionnaire was administered containing demographic variables and about the pathology, child development, education, genetic counseling and neonatal screening. We evaluated patients between 6 months and 16 years of age. The statistical analysis used the chi-square test and ANOVA to assess the association between year of diagnosis and control of phenylalanine and logistic regression to assess the combined effect of age at diagnosis and control of phenylalanine on the developmental delay. Results: From 1986 to 2003, 418 children tested positive for phenylalanine. Of these, 351 (84.0%) had normal results in the second sample, 58 (13.9%) were considered with hyperphenylalaninemia, and 9 (2.1%) were lost for follow-up . The coverage of the program was 50%. Concerning genetic counseling, 39 respondents (72.2%) reported not knowing, not remembering or gave incorrect answers. Conclusion: There was no historical trend of diagnosis having become earlier or of laboratory control having improved. The biochemical control of phenylalanine was dependent on patient age rather than on early diagnosis.

Atendimento ambulatorial em genética em um hospital universitário do RS / Outpatient care in genetics in a university hospital in RS

Introdução: A prevalência de defeitos congênitos e doenças genéticas na América Latina é similar ao resto do mundo e um dos grandes problemas é a ausência de dados epidemiológicos. No Brasil e no restante da América Latina, os serviços de genética estão concentrados em cidades grandes e, em sua maioria, são financiados pelo sistema público. O presente estudo teve por objetivos determinar a frequência das doenças genéticas no ambulatório da FAMED-FURG, avaliar os motivos de referência ao serviço e verificar a procedência dos pacientes encaminhados e os exames necessários para sua investigação. Métodos: Foi elaborada uma ficha padronizada contendo variáveis demográficas e sobre o atendimento, preenchida ao final das consultas. Os dados obtidos foram analisados no programa Epi-Info. Resultados: No período do estudo, (janeiro de 2001 a dezembro de 2003 e março de 2006 a dezembro 2010) 305 pacientes foram avaliados. A maioria dos pacientes era procedente de Rio Grande e cerca de 50% deles foi encaminhado por apresentar aparência sindrômica, atraso no desenvolvimento ou alterações na triagem neonatal. O cariótipo foi solicitado para mais de 30% dos pacientes e a investigação para erros inatos do metabolismo, para 10%. As doenças de etiologia gênica foram as mais frequentes, seguidas das anomalias cromossômicas. Mais de 20% ainda permanecem em investigação, a maioria destes com retardo mental. Conclusão: O atendimento ambulatorial de genética em Rio Grande evitou o deslocamento de pacientes e seus acompanhantes, facilitando o monitoramento e reduzindo custos para o SUS.

Introduction: The prevalence of birth defects and genetic diseases in Latin America is similar to the rest of the world, and one of the major problems is the lack of epidemiological data. In Brazil and the rest of Latin America, genetic services are concentrated in large cities and are mostly funded by the public system. The present study was designed to determine the frequency of genetic diseases in the outpatient care unit of FAMED-FURG, to assess the reasons for reference to the service, and to check the origin of the referred patients and the exams required for their assessment. Methods: We developed a standardized form containing demographic and care-related information, which was completed at the end of the visits. Data were analyzed using Epi-Info. Results: During the study period (January 2001 to December 2003 and March 2006 to December 2010), 305 patients were evaluated. Most patients were originally from the city of Rio Grande, and about 50% of them were referred because of syndromic appearance, developmental delay, or changes in neonatal screening. The karyotype was requested from more than 30% of the patients, and research for inborn errors of metabolism from 10%. Disorders of genic etiology were the most frequent, followed by chromosomal abnormalities. More than 20% are still under investigation, most of those with mental retardation. Conclusion: The genetics outpatient service in Rio Grande avoided the transfer of patients and their companions, thus facilitating their monitoring and reducing costs to the SUS.

PROGRESSIVE OSSIFYING FIBRODYSPLASIA: CASE REPORT.

Progressive ossifying fibrodysplasia is a rare genetic disease that affects one individual in every two million births. Its main consequence is heterotopic ossification, i.e. formation of additional bone in abnormal locations. It is an autosomal dominant disease, usually caused by a new mutation in the ACVR1 receptor gene, which is in the signaling pathway for bone morphogenic protein. This abnormality is not related to gender, ethnicity or consanguinity. The present study reports the case of A.C., a 17-year-old girl. Her clinical investigation began at the age of four years, but she was only diagnosed with FOP at the age of 15 years, after being evaluated by several specialists in different centers. The patient has two siblings, but her family history did not reveal any similar cases.

Fibrodisplasia ossificante progressiva: relato de caso / Progressive ossifying fibrodysplasia: case report

A fibrodisplasia ossificante progressiva (FOP) é uma doença genética rara, atinge um indivíduo a cada dois milhões de nascimentos e tem como principal consequência a ossificação heterotópica: formação de ossos extras em locais indevidos. Trata-se de uma doença autossômica dominante, geralmente resultado de uma mutação nova no gene do receptor ACVR1 no caminho da sinalização da proteína osteomorfogênica. Esta anormalidade não tem relação com sexo, etnia ou consanguinidade. O presente trabalho relata o caso de de A.C., 17 anos, cuja investigação iniciou-se aos quatro anos de idade, mas cujo diagnóstico de FOP foi firmado aos 15 anos, depois de passar por vários especialistas em diferentes centros. A paciente faz parte de uma família de três irmãos, cuja antecedência não revela casos semelhantes.

Progressive ossifying fibrodysplasia is a rare genetic disease that affects one individual in every two million births. Its main consequence is heterotopic ossification, i.e. formation of additional bone in abnormal locations. It is an autosomal dominant disease, usually caused by a new mutation in the ACVR1 receptor gene, which is in the signaling pathway for bone morphogenic protein. This abnormality is not related to gender, ethnicity or consanguinity. The present study reports the case of A.C., a 17-year-old girl. Her clinical investigation began at the age of four years, but she was only diagnosed with FOP at the age of 15 years, after being evaluated by several specialists in different centers. The patient has two siblings, but her family history did not reveal any similar cases.

Risk factors for suspected developmental delay at age 2 years in a Brazilian birth cohort.

Many children are at risk of not achieving their full potential for development. Epidemiological studies have the advantage of being able to identify a number of associated factors potentially amenable to intervention. Our purpose was to identify risk factors for suspected developmental delay (SDD) at age 2 years among all children born in the city of Pelotas, Brazil, in 2004. This study was part of the 2004 Pelotas Birth Cohort. The Battelle Screening Developmental Inventory (BSDI) was administered to cohort children at age 2 years. A hierarchical model of determination for SDD with confounder adjustment was built including maternal sociodemographic, reproductive and gestational characteristics, as well as child and environmental characteristics. Multivariable analysis was carried out using Poisson regression. Prevalence ratios (PR) and 95% confidence intervals [95% CI] were calculated. In the results, 3.3% of the 3869 children studied screened positive for SDD. After confounder control, children more likely to show SDD were: those with positive BSDI at age 12 months (PR = 5.51 [3.59, 8.47]); with 5-min Apgar <7 (PR = 3.52 [1.70, 7.27]); with mothers who had <4 years of schooling (PR = 3.35 [1.98, 5.66]); from social classes D and E (PR = 3.00 [1.45, 6.19]); with a history of gestational diabetes (PR = 2.77 [1.34, 5.75]); born <24 months after the last sibling (PR = 2.46 [1.42, 4.27]); were not told child stories in the preceding week (PR 2.28 [1.43, 3.63]); did not have children's literature at home (PR = 2.08 [1.27, 3.39]); with low birthweight (PR = 1.75 [1.00, 3.07]); were born preterm (PR = 1.74 [1.07, 2.81]); with <6 antenatal care appointments (PR = 1.70 [1.07, 2.68]); with history of hospitalisation (PR = 1.65 [1.09, 2.50]); and of male sex (PR = 1.43 [1.00, 2.04]). These risk factors may constitute potential targets for intervention by public policies and may provide help to paediatricians in preventing developmental delay.