This article summarizes the significant contributions of Fred H. Bess to the early detection of hearing loss in infants and children. Based on public health and educational policy, Bess challenged audiologists to view hearing screening as a responsibility that brought with it the need to develop screening tools that are effective in identifying hearing loss - whether for use with infants, preschoolers, or school-age children - and that adhere to important screening principles. A review of his influence on pertinent guidelines, position statements, and recommendations highlights his belief that early identification of hearing loss is critical if children are to overcome the significant obstacles presented by even mild and unilateral hearing losses. This section is followed by a review of seminal papers that stimulated research in universal newborn hearing screening programs and the detection of unilateral and minimal hearing loss. We conclude with a review of selected studies that build on Bess's earlier work and strive to drive our field forward to practices that are both evidence-based and effective in detecting hearing loss in children.

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CE-ESI-MS has become a powerful analytical tool capable of simultaneous identification and quantification of many classes of biologically relevant molecules. For studies in metabolomics, CE-ESI-MS offers a unique platform which will allow for the systematic elucidation of unknown metabolites in complex matrices without the need for complex sample preparation steps required with other techniques. In this thesis, a novel theoretical prediction model which will allow the estimation of detector response in ESIMS is outlined. This response model will allow researchers to quantitatively predict relative ionization effiency of compounds based on proposed two-dimensional structures without the need for a purified standard. Another feature of this model is that it can be applied to complex biological samples without the need for off-line sample pretreatment. Also in this thesis, a novel neonatal screening method will be presented which will aid clinical chemists in determining the presence of inborn metabolic disorders. This screening method which aims to compliment current protocols will allow health care professionals to further assess dried blood spot samples by providing simultaneous separation, identification, and quantification of relevant metabolites. This method also offers an alternatives to other protocols in place which are necessary to measure acid labile compounds which cannot be assessed by standard screening techniques. / Thesis / Master of Science (MSc)

Background: Recent research is revealing the high rate of false-positive screening results for IEMs in the NICU population. No study published to date has specifically studied the possible relationship between nutrition and newborn screening in this population. Objective: It is suspected that NICU infants who receive PN are more likely to have abnormal newborn screening results than infants who receive EN. An understanding of the role of nutrition will assist in developing protocols for screening in the NICU and decrease false-positives. Design: Infants admitted to the NICU between January 1-June 30, 2009 were included in this retrospective chart review study (n=339). The type of nutrition and timing of its initiation was recorded and compared to newborn screening results to identify correlations with false-positives. Statistical analysis included means, percentages, Fisher's exact test, Chi-square test, and the Cochran-Mantel-Haenszel test. Results: Nutrition type was significantly associated with newborn screening (p<0.001); those who received parenteral nutrition were more likely to have a false-positive. For infants who also received PN, EN of breast milk exclusively increased risk of an abnormal screen more than formula exclusively or breast milk plus formula. The timing of parenteral nutrition had no effect on screening. Premature infants who received PN exclusively had a higher percentage of false-positives than those who received EN Conclusions: Although the hypothesis could not be statistically supported, PN appears to contribute to false-positive newborn screens. More research is needed to ascertain the role of EN and GA in newborn screening and to develop standardized protocols. / Master of Science

Made available in DSpace on 2016-04-27T18:12:08Z (GMT). No. of bitstreams: 1 Tatiana Pinheiro Lima.pdf: 957603 bytes, checksum: e7354554f464ba7abda34a86d31d75c9 (MD5) Previous issue date: 2015-03-17 / Neonatal hearing screening (NHS) aims to identify, as early as possible, the hearing loss in newborns and infants. Two main approaches can be adopted in achieving NHS: in the hospital before discharge, and soon after birth, and when this is not possible, in an outpatient setting, after hospital discharge. Outpatient NHS is adopted mainly in countries where the number of births in hospitals is small, in rural areas, or when there is not a sufficient organization to perform NHS in hospitals. In a country like Brazil, it is important to be able to study the possibility of holding the NHS in an outpatient setting, it s efficiency and effectiveness, and quality indicators in our reality full of economic, health, educational and cultural diversities.Objective: To study the results described in the literature on neonatal hearing screening (NHS) in context outpatient through an integrative review.Method: Integrative review.Search Strategy: Databases: MEDLINE, SciELO, lilac'S and SCOPUS. Selection and inclusion of studies: articles describing the NHS in neonates and infants up to three months of age; which included the site of the NHS; who specified age the day of NHS; who described the tests used and its stages; articles in Portuguese, English and Spanish.Results: It was identified 487 references that met the inclusion criteria. After removal of duplicate studies (83) leaving 404 references, analyzed through the titles and abstracts. Of this total, 292 were excluded because they are research with another theme. Thus, 112 references were selected for reading in reading. Of this total, 70 references were excluded. Of these 42 references were selected for addressing the issue, but 27 references were excluded for not answered any of the guiding questions and address a specific theme. Thus references 15 met all inclusion criteria. Of the 15 selected references 10 refer only to the results of the a outpatient Newborn Hearing Screening five reading to screening systematically held between the neonatal hearing screening in the hospital and outpatient model. The Primary care clinic was the most used room for outpatient approach followed by Health Unit Centers. All studies used the OAE for the test and retest. Conclusion: Few studies describing the outpatient NHS, with reliable and appropriate methodology; The NHS is feasible to perform, especially in primary care, but depends on the organization of the local health system. The age of The outpatient NHS vary between the fourth and 56 day of life of the infant and the prevalence of hearing loss observed in outpatient NHS range from 1.5 to 5.96 / 1000 / A triagem auditiva neonatal (TAN) tem por finalidade a identificação, o mais precoce possível, da deficiência auditiva em neonatos e lactentes. Duas abordagens principais podem ser adotas na realização da TAN: no ambiente hospitalar antes da alta, e logo após o nascimento, e quando esta não é possível, em ambiente ambulatorial, após a alta hospitalar. A TAN ambulatorial é adotada principalmente em países onde o número de nascimentos em hospitais é pequeno, em áreas rurais, ou quando ainda não há uma organização suficiente para a realização da mesma em hospitais. Num país como o Brasil, é importante que se possa estudar a possibilidade da realização da TAN em ambiente ambulatorial, sua eficiência e eficácia, e indicadores de qualidade em nossa realidade repleta de diversidades econômicas, sanitárias, educacionais e culturais. Objetivo: Estudar os resultados descritos na literatura sobre Triagem auditiva neonatal (TAN) em contexto ambulatorial por meio de uma revisão integrativa. Método: Revisão integrativa. Estratégia de busca: Bases de dados: MEDLINE, SCieLO, LILAc S e SCOPUS. Seleção e inclusão dos estudos: artigos que descrevem a TAN em neonatos e lactentes de até três meses de idade; que incluíram o local de realização da TAN; que especificaram idade da realização da TAN; que descreveram os testes utilizados e suas etapas; artigos em português, inglês e espanhol. Resultados: Foram identificada 487 referências que atendiam os critérios de inclusão. Após a remoção dos estudos duplicados (83), restaram 404 referências, analisadas por meio dos títulos e resumos. Deste total, 292 foram excluídos por se tratarem de pesquisas com outro tema. Desta forma, 112 referências foram selecionadas, para leitura na íntegra. Deste total, 70 referências foram excluídas. Destas 42 referências foram selecionadas por tratarem do tema, porém 27 referências foram excluídas por não responderam nenhuma das perguntas norteadoras e por abordar uma temática específica. Assim 15 referências preencheram todos os critérios de inclusão. Das 15 referências selecionadas 10 referem apenas aos resultados da Triagem Auditiva Neonatal Ambulatorial e cinco referentes à triagem realizada sistematicamente entre a triagem auditiva neonatal realizada no modelo hospitalar e ambulatorial. A clínica de Imunização Infantil foi o ambiente mais utilizado para abordagem ambulatorial seguido de Centros de Unidade Básica de Saúde UBS. Todos os estudos utilizaram as EOAE para o teste e reteste. Conclusão: Poucos estudos que descrevem a TAN ambulatorial, com resultados confiáveis e de metodologia adequada; A TAN é viável de ser realizada, principalmente na Atenção Básica, mas depende da organização do Sistema de Saúde local. A idade de realização da TAN ambulatorial variam entre o quarto e o 56º dia de vida do lactente e a prevalência de perda auditiva observada na TAN ambulatorial variam de 1,5 a 5.96/1000

Mitochondrial fatty acid �-oxidation disorders are a group of clinically and biochemically heterogeneous defects mainly associated with intolerance to catabolic stress. The diseases are potentially fatal, but treatable and the prognosis for most diagnosed disorders is generally favourable. Early diagnosis is thus important to prevent morbidity and mortality. This project describes an improved and validated quantitative fibroblast acylcarnitine profile assay for the investigation of suspected fatty acid �-oxidation disorders. Intact cells were incubated with deuterium-labelled hexadecanoate and L-carnitine, and the accumulated acylcarnitines in the medium analysed using electrospray tandem mass spectrometry. This modified procedure is less demanding technically, requires fewer cells and better reflects the in vivo acylcarnitine status than previously published methods. Mitochondrial fatty acid �-oxidation is coupled to the respiratory chain. Functional defects of one pathway may lead to secondary alterations in flux through the other. The diagnostic specificity and the prognostic potential of the in vitro acylcarnitine profile assay were investigated in fibroblasts from 14 normal controls, 38 patients with eight enzyme deficiencies of fatty acid �-oxidation presenting with various phenotypes, and 16 patients with primary respiratory chain defects including both isolated and multiple enzyme complex defects. All fatty acid �-oxidation deficient cell lines revealed disease-specific acylcarnitine profiles related to the sites of defects irrespective of the severity of symptoms or of different mutation. Preliminary studies suggested a correlation between severity of symptoms and higher concentrations of long-chain acylcarnitine species. However, the fibroblast acylcarnitine profiles from some patients with respiratory chain defects were similar to those of controls, whereas others had abnormal profiles resembling those found in fatty acid �-oxidation disorders. In vitro acylcarnitine profiling is useful for the detection of fatty acid �-oxidation deficiencies, and perhaps the prediction of disease severity and prognostic evaluation facilitating decisions of therapeutic intervention and genetic counselling. However, abnormal profiles do not exclusively indicate these disorders, and primary defects of the respiratory chain remain a possibility. Awareness of this diagnostic pitfall will aid in the selection of subsequent confirmatory tests and therapeutic options.

Until first half of the XX century, sickle cell disease was practically limited to the malaria endemic areas and countries having known an important surge of African slaves. Today, migratory flows and progress of medicine have modified considerably the distribution of sickle cell disease which is from now on a frequent affection in Western Europe. The preventive implementation of medical care makes it possible to reduce morbidity and mortality associated with this pathology. Stake of a medical policy and economic interests, neonatal screening for hemoglobin disorders justifies then fully the implementation of powerful and adapted means. In order to initiate a newborn screening programme in our centre, we developed various immunological tests allowing to identify the sickle hemoglobin. We first of all developed an indirect immunoassay and led a population study on 46082 Belgian newborns and 1825 neonates from Central Africa. The performances of this assay were improved thereafter by conceiving a competitive test. Next, for reasons independent of our will, we had unfortunately to abandon the immunological approach. This methodology was thus supplanted in our center by an innovative method for this indication: the mass spectrometry. Our promising results currently authorize us to perennialize our policy in the neonatal screening for sickle cell disease and open the way for new developments in other fields. / Jusquà la première moitié du XXe siècle, la drépanocytose se limitait pratiquement aux zones dendémie palustre et aux pays ayant connu un important afflux desclaves dorigine africaine. Aujourdhui, les flux migratoires et les progrès de la médecine ont considérablement modifié la distribution de cette maladie qui est désormais une affection fréquente en Europe occidentale. La prise en charge précoce permet de réduire la morbidité et la mortalité associées à cette maladie. Enjeu dune politique sanitaire et dintérêts économiques, le dépistage néonatal de la drépanocytose justifie donc ainsi pleinement la mise en uvre de moyens performants et adaptés. Afin dinitier un programme de dépistage au sein de notre centre, nous avons initialement développé divers tests immunologiques permettant didentifier lhémoglobine anormale. Nous avons tout dabord mis au point un immunoessai indirect et conduit une étude de population sur 46082 nouveau-nés belges et 1825 bébés originaires dAfrique centrale. Les performances de lessai ont par la suite été améliorées en concevant un test compétitif. Lapprovisionnement laborieux danticorps nécessaires aux tests de détection a par la suite entravé notre programme. En effet, la commercialisation en a été interrompue et la production danticorps monoclonaux par nos moyens propres na pas été couronnée du succès escompté. Lapproche immunologique du dépistage néonatal de la drépanocytose a ainsi été supplantée dans notre centre par une méthode novatrice pour cette indication : la spectrométrie de masse. Nos résultats prometteurs nous autorisent actuellement à pérenniser notre nouvelle façon de faire dans le dépistage néonatal de la drépanocytose et ouvre la voie pour de nouveaux développements dans dautres domaines.

Texas House Bill 790 resulted in the expansion of the newborn screening panel from 7 to 27 disorders. The long-term economic implications of this expansion have not been studied. The objective of this study was to estimate the incremental cost-effectiveness of the expanded newborn screening program compared to the previous standard screening in Texas. A Markov model (for a hypothetical cohort of Texas births in 2007) was constructed to compare life-time costs and QALYs between the expanded newborn screening and pre-expansion newborn screening. Estimates of costs, probabilities of sequelae, and utilities for disorder categories were obtained from Texas statistics, the literature, and expert opinion. A baseline discount rate of 3% was used for both costs and QALYs, with a range of 0% to 5%. Analyses were conducted from a payer's perspective, so only direct medical cost estimates were included. The life-time incremental cost-effectiveness ratio (ICER) for expanded versus pre-expansion screening was about $12,000/QALY. Probabilistic sensitivity analysis using key variables showed that results ranged from about $9,500 to $13,000 /QALY. This range is well below the commonly cited willingness to pay threshold of $50,000/QALY. Therefore, expanded newborn screening results in additional expense to the payer but also improves patient outcomes by preventing avoidable morbidity and mortality. The screened population benefits from greater QALYs as compared to the unscreened population. Overall, expanded newborn screening in Texas was estimated to be a cost-effective option as compared to unexpanded newborn screening. / text

Mitochondrial fatty acid �-oxidation disorders are a group of clinically and biochemically heterogeneous defects mainly associated with intolerance to catabolic stress. The diseases are potentially fatal, but treatable and the prognosis for most diagnosed disorders is generally favourable. Early diagnosis is thus important to prevent morbidity and mortality. This project describes an improved and validated quantitative fibroblast acylcarnitine profile assay for the investigation of suspected fatty acid �-oxidation disorders. Intact cells were incubated with deuterium-labelled hexadecanoate and L-carnitine, and the accumulated acylcarnitines in the medium analysed using electrospray tandem mass spectrometry. This modified procedure is less demanding technically, requires fewer cells and better reflects the in vivo acylcarnitine status than previously published methods. Mitochondrial fatty acid �-oxidation is coupled to the respiratory chain. Functional defects of one pathway may lead to secondary alterations in flux through the other. The diagnostic specificity and the prognostic potential of the in vitro acylcarnitine profile assay were investigated in fibroblasts from 14 normal controls, 38 patients with eight enzyme deficiencies of fatty acid �-oxidation presenting with various phenotypes, and 16 patients with primary respiratory chain defects including both isolated and multiple enzyme complex defects. All fatty acid �-oxidation deficient cell lines revealed disease-specific acylcarnitine profiles related to the sites of defects irrespective of the severity of symptoms or of different mutation. Preliminary studies suggested a correlation between severity of symptoms and higher concentrations of long-chain acylcarnitine species. However, the fibroblast acylcarnitine profiles from some patients with respiratory chain defects were similar to those of controls, whereas others had abnormal profiles resembling those found in fatty acid �-oxidation disorders. In vitro acylcarnitine profiling is useful for the detection of fatty acid �-oxidation deficiencies, and perhaps the prediction of disease severity and prognostic evaluation facilitating decisions of therapeutic intervention and genetic counselling. However, abnormal profiles do not exclusively indicate these disorders, and primary defects of the respiratory chain remain a possibility. Awareness of this diagnostic pitfall will aid in the selection of subsequent confirmatory tests and therapeutic options.