INTRODUCTION: Gastrointestinal pathologies are a common etiology of organic failure to thrive and feeding difficulties; therefore failure to thrive can be a common indication for esophagogastroduodenoscopy (EGD), especially in infants and young children. However there has been no recent studies investigating diagnostic outcome of EGD in children specifically with failure to thrive or feeding difficulties. AIM: To investigate the outcome of EGD with biopsy in children presenting with failure to thrive or feeding difficulties and to determine the extent to which EGD with biopsy results led to a change in diagnosis or clinical management, including medication and nutritional supplements. METHODS: We performed a retrospective cohort study in children under the age of 3 (defined as from 0 up to and including 36 months) who had been seen at one of Boston Children’s Hospital’s outpatient gastroenterology clinics and undergone EGD for the investigation of failure to thrive or feeding difficulties from 1 January 2015 to 31 December 2015. RESULTS: Poor weight gain (55.6%), gastroesophageal reflux (44.4%) and food refusal (38.9%) were the most common presenting symptoms at the first GI clinic visit. The overall prevalence of any gross endoscopic abnormality was 24.8%. The overall prevalence of any histologic abnormality was 44.2%. Compared to subjects with normal esophageal histology, subjects with abnormal esophageal histology had a lower proportion of gastroesophageal reflux and vomiting as their main presenting symptom (63.4% vs. 44.4%, p-value = 0.04). Compared to subjects with normal esophageal histology, subjects with histologic abnormalities in the esophagus were more likely to have current allergy to milk (25% vs. 9.6%, p = 0.02), peanut (8.3% vs. 1.1%, p = 0.03) and tree nut (8.3% vs. 1.1%, p = 0.03). CONCLUSION: In this study gastroesophageal reflux was more prevalent in subjects with normal esophageal histologic findings than those with abnormal findings (63.4% vs. 44.4%, p-value = 0.04). Although the largest number of histologic abnormalities were found in infants, infants were still more likely to have normal than abnormal histology in the esophagus. This finding suggests a more a careful consideration of signs and symptoms prior to proceeding with EGD in infants. Subjects with current milk allergy were more likely to have esophageal histologic abnormalities (p-value = 0.02). Further analysis could indicate current milk allergies as a predictive variable in esophageal histologic abnormalities.

The efficacy of multidisciplinary inpatient and outpatient treatment for transitioning children with severe pediatric feeding disorders from gastrostomy tube dependency to oral nutrition was investigated utilizing caloric and fluid intakes as an outcome measure. The study involved 29 children ages 12 months to 5 years of age with gastrostomy tube dependency. Treatments were provided by speech therapists, occupational therapist, dietician and psychologist for a 30 day period. Four treatment groups were evaluated and average intakes compared at 4 observation periods including pretreatment, initiation of treatment, completion of treatment at 30 days and 4 month follow-up. Children receiving inpatient treatment for feeding disorders evidenced significant differences in oral caloric intake from pretreatment to discharge than outpatient treatment (p < .01) and wait list control group (p = .04). Oral caloric intake from discharge to 4 month follow up yielded no significant differences indicating treatment gains were maintained. Change in environment and caretaker showed a significant effect for the inpatient group (d = 1.89). Effects of treatment by age and weight at 4 month follow up were also analyzed.

The traditional role of speech-language therapists as feeding specialists appears to have focused primarily on the mechanics of feeding disorders, without fully considering the impact of nutritional needs on a child's development and communication. The aim of the study was to investigate the experiences and perceptions of a group of speech-language therapists regarding nutritional issues in children requiring feeding therapy or early communication intervention. A qualitative research design was employed in the form of a descriptive survey and a questionnaire was compiled as the data collection instrument. Forty-nine questionnaires were delivered to speech-language therapists within the Johannesburg and Pretoria geographical areas, of which 32 were suitable for analysis. Closed ended questions were analyzed quantitatively using descriptive statistics while responses to open-ended questions were categorized thematically. Results indicated that all respondents came into contact with clients who had, or who were at risk for, feeding disorders and nutritional deficiencies. However, findings revealed that during assessment and treatment of these clients, respondents tended to neglect issues related to nutrition, as well as psychosocial issues pertinent to feeding disorders. Furthermore, respondents appeared not to have fully realized the importance of their role as communication specialists within the feeding context. It was found that the majority of respondents were involved within a multidisciplinary team approach; however, the application of the more effective transdisciplinary approach was limited. This was confirmed by results revealing that collaboration with other professionals, such as dieticians, did not consistently occur. In terms of training, it was evident that respondents received the majority of their training in feeding therapy from continued education, which included aspects of nutrition. However, undergraduate training was perceived as having limitations within the theoretical content as well as practical application, and did not incorporate nutritional aspects. In light of the apparent need for a more holistic view of paediatric clients with feeding disorders, suggestions were made regarding the inclusion of vital nutritional issues and psychosocial factors within training and transdisciplinary service delivery in South Africa. Furthermore, relevant research topics within the field of paediatric feeding were presented. Broadening perspectives by means of holistic research and training may enhance service delivery to children with paediatric feeding disorders. / Dissertation (MCommPath)--University of Pretoria, 2002. / tm2015 / Speech-Language Pathology and Audiology / MCommPath / Unrestricted

No description available.

No description available.

M.Ed. / Failure-to-thrive syndrome presents itself as severely inadequate weight increase in children under the age of five without any organic aetiology. It is found particularly in developing countries, constituting about half the malnutrition figures for children under five. Failure-to-thrive research has shown that this is a complex syndrome for which it is difficult to find an aetiology. There are frequently signs of disrupted emotional bonding between mother and child, as well as problematic mother-child interactions. However, the maternal attributes which contribute to the phenomenon are not yet fully understood. Intervention is usually unsuccessful. This study aims to investigate the role of the mother in order to increase understanding of the failure-to-thrive phenomenon. The research design is qualitative, explorative, descriptive and contextual. A multiple casestudy method was used. Three mothers were selected for the study. Data was gathered by means of interviews, supplemented by the observation of interactions and the researcher's own impressions. The interviews were videotaped in their entirety, and were transcribed verbatim afterwards. All data sources were synthesised in the form of case studies. Then the data was interpreted in the light of object-relation theory. The results suggest the importance of several factors already present before the birth of the child, including inadequate emotional care during the mothers' own childhood, and maternal inability to control their emotions. In all the cases studied, the pregnancy was unplanned and additional external stressors made the pregnancy more difficult. These mothers experienced their children as a threat, as competition or as symbols of their powerlessness. These mothers described their children as "wild" and demanding. Observation of interactions indicated that this type of behaviour in the children may be an attempt to attain affection from their mothers, or an anxious reaction to the mothers' inability to set limits. The restlessness of these children exacerbated the mothers' sense of inadequacy and contributed to a vicious cycle. These mothers were unable to provide what Winnicott describes as "good enough mothering". They were too emotionally needy themselves. Observations of interactions revealed an inability to adjust to the needs relevant to the children's age groups, inadequate responsiveness, inconsistency, instrumental care and a lack of involvement. It appeared that these mothers had themselves not been mothered enough during their own early development, so that they could not internalise these attributes. Their descriptions suggest inadequate environmental provision for what babies need in their first year of life to experience the world as a secure place, to reach personal integration and to interact trustfully with others. This early deprivation of the mother obviously has implications for the way these women treat their own children at the age when these mothers themselves were neglected as children. Suggested intervention tends to focus on support and mothering for the mothers, but the most appropriate type of intervention is individual psychotherapy which allows adequate internalisation of the "good mother" image. This would facilitate personal integration, enabling the mother to focus on her child's needs, freed from her own.

INTRODUÇÃO: Crianças com baixa estatura constituem um grupo heterogêneo. Em uma parcela dos casos, o mecanismo envolvido nesse processo decorre de alterações genéticas. OBJETIVO: Realizar uma investigação clínica e genético-molecular de um grupo de pacientes com baixa estatura de causa desconhecida. MÉTODOS: Selecionamos crianças com baixa estatura persistente (escore-Z de altura <= -2 para idade e sexo) de causa desconhecida para avaliação genômica. O estudo foi dividido em 2 etapas: 1ª etapa - avaliação de 229 pacientes com baixa estatura sindrômica [baixa estatura associada a outros achados dismórficos (atraso de desenvolvimento neuropsicomotor e/ou déficit intelectual, presença de dismorfismos faciais e/ou outras malformações)] por cariótipo molecular (aCGH/SNPa); 2ª etapa: avaliação de 99 crianças com baixa estatura persistente, nascidas pequenas para idade gestacional (PIG - escore-Z de peso e/ou comprimento ao nascer <= -2 para idade gestacional) e classificação de acordo com a presença ou ausência de dismorfismos associados. Essas crianças foram divididas em dois grupos: baixa estatura sindrômica (n=44) e baixa estatura isolada (n=55). Pacientes com baixa estatura sindrômica foram avaliados por sequenciamento exômico (WES). Pacientes com baixa estatura isolada foram avaliados através de painel gênico (n = 39) ou WES (n = 16). RESULTADOS: 1ª etapa: 32 (14%) pacientes com baixa estatura sindrômica apresentaram variações no número de cópias (CNVs) patogênicas ou possivelmente patogênicas. Sete delas são recorrentes em outros estudos e são responsáveis por cerca de 40% de todas as CNVs patogênicas/possivelmente patogênicas encontradas em pacientes com baixa estatura de causa desconhecida. 2ª fase: Dentre os 99 pacientes avaliados com baixa estatura nascidos PIG, foram encontradas 23 variantes patogênicas/possivelmente patogênicas em genes já associados à distúrbios de crescimento. Quinze (34%) nos pacientes com baixa estatura sindrômica, em genes relacionados a processos celulares fundamentais, vias de reparo de DNA e vias intracelulares; e oito (15%) em pacientes com baixa estatura isolada, em genes associados à cartilagem de crescimento e a via RAS/MAPK. CONCLUSÃO: A heterogeneidade dos pacientes com baixa estatura dificulta o diagnóstico clínico. As novas abordagens genômicas permitem estabelecer o diagnóstico etiológico de crianças com baixa estatura de causa desconhecida / BACKGROUND: Patients born small for gestational age (SGA) are a heterogenous group, and in several cases, it is due to genetic processes. AIM: To perform a clinical and genetic-molecular investigation of short stature patients of unknown cause. METHODS: We selected short stature children (height <= -2 SDS for age and sex) of unknown cause for genomic evaluation. The study had two stages: 1st stage - 229 syndromic short stature patients (patients with short stature and dysmorphic features, developmental delay, and/or intellectual disability) were evaluated by molecular karyotype (aCGH/SNPa); 2nd stage: We selected 99 short stature children born SGA (birth weight and/or length <=-2 SDS for gestational age). They were classified according to the presence or absence of dysmorphic features into two groups: syndromic short stature (n=44) and isolated short stature (n=55). Patients with syndromic short stature were evaluated by whole exome sequencing (WES), and patients with isolated short stature were evaluated through a target panel sequencing (n=39) or WES (n=16). RESULTS: 1st stage: 32 (14%) syndromic short stature patients had pathogenic or probably pathogenic copy number variations (CNVs). We observed seven recurrent CNVs that are responsible for about 40% of all pathogenic/probably pathogenic genomic imbalances found in short stature patients of unknown cause. 2nd stage: Of the 99 patients evaluated, 23 pathogenic/likely pathogenic variants were found in genes already associated with growth disorders. Fifteen (34%) syndromic short stature patients had pathogenic variants in genes related to fundamental cellular processes, DNA repair and intracellular pathways; and eight (15%) isolated short stature patients had pathogenic variants in genes associated with growth plate development and the RAS/MAPK pathway. CONCLUSION: The heterogeneity of short stature makes the clinical diagnosis difficult. The new genomic approaches are effective to diagnose a larger number of undiagnosed patients

Introdução: Crianças nascidas pequenas para a idade gestacional (PIG) apresentam maior risco de permanecerem com baixa estatura na vida adulta. Os fatores de crescimento insulino-símile tipo 1 e 2 (IGF-1 e IGF-2) são os principais fatores endócrinos determinantes do crescimento fetal. A maioria das ações conhecidas destes hormônios é mediada via um receptor tirosina quinase, conhecido como IGF-1R. As mutações inativadoras e deleções do gene do IGF1R em heterozigose vêm sendo relatadas de forma crescente nos últimos 9 anos em pacientes com história de déficit de crescimento pré e pós-natal. Postula-se que pelo menos 2 a 3% das crianças nascidas PIG poderiam apresentar defeitos no IGF1R. O quadro clínico destes pacientes apresenta grande variabilidade quanto à gravidade do retardo de crescimento pré- e pós-natal e aos parâmetros hormonais. Objetivo: Caracterizar in vitro a resistência ao IGF-1 de pacientes com defeitos no IGF1R, identificados em nosso ambulatório. Material e métodos: Desenvolvemos cultura de fibroblastos de 2 controles (C1 e C2) e de 4 pacientes nascidos PIG (SGA1, SGA2, SGA3 e SGA4) com suspeita de insensibilidade ao IGF-1 por ausência de recuperação do crescimento na vida pós natal. Destes pacientes, um paciente (SGA1) era portador de mutação missense em heterozigose no gene IGF1R (p.Arg511Trp) e os demais apresentavam baixa expressão dos IGF1R em leucócitos periféricos quando avaliados por PCR em tempo real. Um destes pacientes (SGA2) apresentava também a variante alélica p.Gly6Arg do IGF1R em heterozigose, alteração esta encontrada também em controles e familiares sem déficit de crescimento. As ações do IGF-1 foram determinadas por ensaios de proliferação, análise da expressão do IGF-1R e estudos de fosforilação de proteínas da via de sinalização do IGF-1 em fibroblastos (via PI3K). Resultados: As linhagens SGA1, SGA2, SGA3 e SGA4 proliferaram respectivamente 55%, 66%, 64% e 28% a menos sob estímulo de IGF-1 em relação ás linhagens controles. No estudo da expressão do RNAm do IGF1R por PCR em tempo real, foi observada redução na expressão do IGF1R nas linhagens SGA2, SGA3 e SGA4 em relação aos controles, assim como o conteúdo total da proteína IGF-1R. Por outro lado, a linhagem SGA1 mostrou expressão aumentada do IGF1R e no conteúdo da proteína em relação aos controles. Em relação á ativação da via PI3K, todas as linhagens dos pacientes apresentaram menor fosforilação de AKT após estímulo com IGF-1, quando comparadas com as linhagens controles. Conclusão: Demonstramos a presença de insensibilidade parcial ao IGF-1 nas linhagens estudadas. A baixa expressão do IGF1R observada em leucócitos periféricos nas linhagens SGA2, SGA3 e SGA4 foi confirmada em fibroblastos tanto em nível de RNAm quanto da sua proteína. Nestas linhagens a insensibilidade ao IGF-1 é secundária a diminuição da expressão deste receptor. Em contraste a na linhagem com a mutação p.Arg511Trp (SGA1) observou-se expressão normal do IGF-1R na superfície celular. Pacientes com alterações no gene IGF1R não apresentam um fenótipo característico que os diferencie de outras crianças nascidas PIG sem alterações neste gene, mostrando a importância dos estudos moleculares neste grupo de pacientes / Small for gestational age (SGA) children are at a greater risk of having a short stature in adulthood. The type 1 and 2 insulin-like growth factors (IGF-1 and IGF-2) are the main endocrine factors determining fetal growth, and most of the known actions of these hormones are mediated via a receptor tyrosine kinase, IGF-1R. Inactivating mutations and deletions of the IGF1R gene in heterozygosis have been reported with increasing frequency in the last 9 years in patients with a history of a failure to thrive pre- and postnatally. It is postulated that at least 2-3% of the children born SGA could be defective for the IGF1R. The clinical presentation of these patients is highly variable with regard to the severity of growth retardation and pre- and post-natal hormonal parameters. Objectives: The goal of this study was to identify the in vitro insensitivity to IGF-1 in patients with defects in IGF1R. Methods: We developed fibroblast cultures from two controls (C1 and C2) and 4 patients born SGA (SGA1, SGA2, SGA3 and SGA4) with a suspected insensitivity to IGF-1 by the absence of catch-up growth during their postnatal life. Of these patients, one (SGA1) carried a heterozygous missense mutation in the IGF1R gene (p.Arg511Trp), and the others exhibited low expression levels of IGF1R in their peripheral leukocytes, as evaluated using real-time PCR. One of these patients (SGA2) was also heterozygous for the allelic variant p.Gly6Arg of IGF1R, an alteration also found in the controls and family members not displaying growth restriction. The actions of IGF-1 were determined using proliferation assays, an analysis of the expression of IGF- 1R and phosphorylation studies of proteins of the IGF-1 signaling pathway in fibroblasts (via PI3K).Results: The SGA1, SGA2, SGA3 and SGA4 fibroblasts proliferated 55%, 66%, 64% and 28%, respectively, less under the stimulation of IGF-1 compared to the control lines. Using real-time PCR, the IGF1R mRNA expression showed reduced levels of IGF1R in the SGA2, SGA3 and SGA4 cells compared to the controls, and the total IGF-1R protein was also decreased in these cells. Moreover, the SGA1 cells showed increased expression levels of IGF1R mRNA and protein compared to the controls. In relation to the activation of PI3K, all of the cells showed decreased phosphorylation of AKT after the stimulation with IGF-1 compared to the control cells. Conclusion: We demonstrated the presence of a partial insensitivity to IGF-1 in the studied samples. The low expression of IGF1R observed in the peripheral leukocytes in the SGA2, SGA3 and SGA4 fibroblasts was confirmed at both the mRNA and protein levels, and the Andréa de Castro Leal Doutorado insensitivity of the cells to IGF-1 is secondary to the decreased expression of the receptor. In contrast, the cells with the mutation p.Arg511Trp (SGA1) displayed normal IGF-1R expression on the cell surface. The patients with alterations in the IGF1R gene do not exhibit a characteristic phenotype that differentiates them from other children born SGA and with no changes in this gene, thus showing the importance of molecular studies for this group of patients

Crianças nascidas pequenas para a idade gestacional (PIG) apresentam maior risco de permanecerem com baixa estatura na vida adulta. Os fatores de crescimento insulina-símile 1 e 2 (IGF-1 e IGF-2) são os principais fatores endócrinos determinantes do crescimento fetal. Na vida pós-natal o GH, principal hormônio promotor de crescimento, exerce a maior parte de seus efeitos por meio do IGF-1. A grande maioria das ações conhecidas do IGF-1 e IGF-2 são mediadas via receptor tirosina quinase conhecido como receptor tipo 1 de IGFs (IGF-1R). Os objetivos deste trabalho foram estudar os genes IGF1 e IGF1R em crianças nascidas pequenas para a idade gestacional que não recuperaram o crescimento na vida pós-natal. Foram selecionados 145 pacientes nascidos PIG, 72 sem catch up e 73 com catch up. Em 54 PIG sem catch up foi estudado toda a seqüência codificadora do gene IGF1 por meio de PCR e seqüenciamento direto, nos demais PIG sem catch up e nos 73 PIG com catch up foi estudado apenas o exon 6 do IGF-1 por PCR e seqüenciamento direto para avaliação de um polimorfismo encontrado nesta região. Nos pacientes que apresentavam concentração sérica de IGF-1 e IGFBP-3 acima da média para idade e sexo e seqüência do IGF1 normal (n=23) foi realizada coleta de sangue periférico com posterior separação de leucócitos mononucleares pelo gradiente de ficoll seguido por extração de RNA pelo método de Trizol® Posteriormente, a partir do RNA, sintetizamos o cDNA (DNA complementar) utilizando primers randômicos. Foi realizado PCR e seqüenciamento direto do cDNA, além de análise da expressão do IGF1R por PCR em tempo real. Nenhuma mutação foi encontrada no gene IGF1. Entretanto um locus altamente polimórfico foi encontrada na região 3\' não traduzida do exon 6 deste gene, região esta envolvida no processo de poliadenilação. A freqüência das variantes alélicas foi semelhante em PIG com e sem catch-up e em controles nascidos AIG. Analisando o fenótipo de pacientes PIG que apresentavam a variante alélica wild type ou uma das três variantes alélicas mais freqüentemente encontradas, não observamos diferenças significativas entre peso e comprimento ao nascimento, níveis de IGF-1 e crescimento na vida pós-natal. No gene IGF1R encontramos duas variantes alélicas nunca descritas previamente. A primeira variante encontrada está localizada no exon 1, em uma região de peptídeo sinal do pro IGF-1R e consiste na troca do nucleotídeo guanina pelo nucleotídeo adenina na posição 16 da região codificadora (c.16G>A), levando a troca do aminoácido glicina por arginina na posição 6 da proteína (p.G6R). A outra mutação encontrada está localizada no exon 7 onde observamos uma troca do nucleotídeo citosina por timina na posição 1531 do cDNA (c.1531 C>T), levando a uma troca de arginina por triptofano na posição 511 do IGF1R (p.R511W). Adicionalmente, foi observada uma expressão do IGF1R diminuída em 5 pacientes estudados.Concluímos que as variantes alélicas encontradas na região de poliadenilação do IGF1 não influenciam significativamente as características ao nascimento e pós-natais de crianças nascidas PIG ou a altura adulta de indivíduos normais nascidos AIG. O estudo do IGF1R identificou duas novas variantes alélicas em heterozigose no gene IGF1R e, em cinco pacientes, observamos uma expressão reduzida deste gene. Pacientes com alterações no gene IGF1R não apresentam um fenótipo característico que os diferencie de outras crianças nascidas PIG sem alterações neste gene, mostrando a importância dos estudos moleculares. / Children born small for gestational age (SGA) have a higher risk of remaining short in adulthood. The insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) are the main factors determining endocrine fetal growth. GH is the main promoter of linear growth in the postnatal life, exerting its effects mostly through the IGF-1. The vast majority of known actions of IGF-1 and IGF-2 are mediated by the insulin-like growth factor type 1 receptor (IGF-1R), a member of the tyrosine kinase receptors family. The aim of this study was to investigate IGF1 and IGF1R genes mutations in children born small for gestational age without catch up growth in postnatal life. We selected 145 patients born SGA, 72 without catch-up and 73 with catch up. The whole coding region of the IGF1 gene was sequenced in 54 patients without catchup. In the other SGA children without catch-up and in 73 SGA with catch-up, only the exon 6 of IGF1 was sequenced to assess the influence of allelic variants present in this region. In patients with normal IGF1 sequence and IGF-1 and IGFBP-3 serum levels above the mean for age and sex (n = 23) total RNA was extracted from peripheral blood lymphocytes followed by cDNA synthesis with random primers. The IGF1R cDNA was amplified using specific primers followed by direct sequencing. IGF1R expression was analyzed by real-time PCR. No mutations were found in the IGF1 gene. However a highly polymorphic sequence was identified in the upstream core polyadenylation signal (UCPAS) located in IGF1 3\' UTR at exon 6. The frequency of the identified allelic variants was similar in SGA children with and without catch-up and in controls. Furthermore, children homozygous for the wild-type allele and those carrying the allelic variants in homozygous or heterozygous state presented similar weight and length at birth, as well as serum IGF-1 levels and postnatal growth features. Two novel nonconservative allelic variants were identified in IGF1R in 23 SGA children (8.7%) in the heterozygous state. The first variant (c.16G>A) was located in the exon one, leading to a substitution of glicine by arginine in the pro-IGF-1R signaling peptide (p.G6R). The second variant was located in exon 7 (c.1531 C>T), leading to a substitution of arginine by tryptophan in the amino acid 511 of the IGF1-R (p.R511W). Moreover, a decreased IGF1R expression was observed in 5 of the 23 patients with elevated serum IGF-1 concentrations. We conclude that the UCPAS allelic variants did not significantly influence the birth and postnatal characteristics of children born SGA, neither the adult height of normal individuals born adequate for gestational age. The IGF1R study identified two novel allelic variants in two patients and a reduced expression of the IGF1R was observed in five patients. Patients with alterations in IGF1R did not have a distinctive phenotype when compared with other children born SGA without changes in this gene, indicating the importance of molecular studies.

No description available.