Leung, Wan Lun Fiona. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 179-204). / Abstracts in English and Chinese. / Abstract --- p.i / 中文摘要 --- p.v / Acknowledgement --- p.viii / List of Abbreviations and Symbols x --- p.vi / List of Tables --- p.xx / List of Figures --- p.xxi / Chapter CHAPTER ONE --- Introduction --- p.1 / Chapter 1.1 --- General Overview --- p.1 / Chapter 1.2 --- Necrotizing Enterocolitis (NEC) --- p.3 / Chapter 1.2.1 --- Epidemiology of NEC --- p.3 / Chapter 1.2.2 --- "Clinical Presentation, Diagnosis and Management of NEC" --- p.5 / Chapter 1.2.3 --- Pathophysiology of NEC --- p.9 / Chapter 1.2.3.1 --- Prematurity --- p.9 / Chapter 1.2.3.2 --- Bacterial Colonization --- p.12 / Chapter 1.2.3.3 --- Enteral Feeding --- p.15 / Chapter 1.2.3.4 --- Hypoxia and Ischemia --- p.16 / Chapter 1.2.3.5 --- Genetic Polymorphism --- p.17 / Chapter 1.2.3.6 --- Inflammatory Mediators --- p.20 / Chapter 1.3 --- Spontaneous Intestinal Perforation (SIP) --- p.24 / Chapter 1.3.1 --- Epidemiology of SIP --- p.24 / Chapter 1.3.2 --- "Clinical Presentation, Diagnosis and Management of SIP" --- p.26 / Chapter 1.3.3 --- Risk Factors of SIP --- p.28 / Chapter 1.3.3.1 --- Prematurity --- p.29 / Chapter 1.3.3.2 --- Use of Drugs --- p.30 / Chapter 1.4 --- Comparison between NEC and SIP --- p.32 / Chapter 1.5 --- Role of Cytokines in Pathogenesis of NEC and SIP --- p.38 / Chapter 1.6 --- Immunoregulatory Molecules of Interest in This Study --- p.46 / Chapter 1.6.1 --- Angiopoietin-2 (Ang-2) --- p.46 / Chapter 1.6.2 --- v-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog 2 (avian) (ErbB3) --- p.48 / Chapter 1.6.3 --- Type II Interleukin-1 Receptor (IL-1RII) --- p.52 / Chapter 1.6.4 --- Urokinase Plasminogen Activator Receptor (uPAR) --- p.54 / Chapter CHAPTER TWO --- Objectives --- p.57 / Chapter CHAPTER THREE --- Materials and Methodology --- p.58 / Chapter 3.1 --- Overview of the Experimental Procedures --- p.58 / Chapter 3.1.1 --- Investigation on the Profile of Circulatory Immunoregulatory Proteins in Plasma of NEC and SIP High Risk Neonates --- p.58 / Chapter 3.1.2 --- Investigation on the mRNA Expression Level of Targeted Immunoregulatory Molecules on Resected Intestinal Tissues in NEC and SIP Neonates --- p.58 / Chapter 3.1.3 --- Investigation on the mRNA and Protein Expression Levels of Targeted Immunoregulatory Molecules in Human Intestinal Cell Lines --- p.60 / Chapter 3.2 --- Reagents and Lab-wares with Their Sources --- p.61 / Chapter 3.3 --- Study Population --- p.63 / Chapter 3.4 --- Collection of Neonatal Whole Blood Samples --- p.65 / Chapter 3.5 --- Cytokine Antibody Array Analyses --- p.67 / Chapter 3.6 --- Enzyme-linked Immunosorbant Assays (ELISA) --- p.69 / Chapter 3.6.1 --- Angiopoietin-2 --- p.69 / Chapter 3.6.2 --- sErbB3 --- p.71 / Chapter 3.6.3 --- sIL-lRII --- p.72 / Chapter 3.6.4 --- suPAR --- p.74 / Chapter 3.7 --- Collection of Neonatal Resected Intestinal Tissues --- p.76 / Chapter 3.8 --- Resected Intestinal Tissue RNA Isolation --- p.78 / Chapter 3.9 --- Purity Assessment of the Purified Tissue RNA Samples --- p.80 / Chapter 3.10 --- Integrity Assessment of the Purified Tissue RNA Samples --- p.81 / Chapter 3.11 --- In vitro Stimulation of Human Enterocytes by Lipopolysaccharides (LPS) and/or Platelet Activating Factor (PAF) --- p.84 / Chapter 3.12 --- mRNA Expression Level Assessment of Selected Target Genes in Resected Intestinal Tissues and Human Intestinal Cell Lines --- p.86 / Chapter 3.12.1 --- Synthesis of First Strand cDNA --- p.86 / Chapter 3.12.2 --- Quantitative Polymerase Chain Reaction (qPCR) --- p.87 / Chapter 3.13 --- Statistical Analysis --- p.89 / Chapter CHAPTER FOUR --- Screening of Immunoregulatory Target Protein Molecules in Plasma of NEC and SIP Patients by Cytokine Array Analyses --- p.104 / Chapter 4.1 --- Results --- p.104 / Chapter 4.1.1 --- Screening of Detectable Immunoregulatory Target Molecules --- p.104 / Chapter 4.1.2 --- Selection of Target Molecules Based on the Fold Change in NEC or SIP Compared with Control Samples --- p.105 / Chapter 4.1.2.1 --- Similar Regulation of Target Molecules in Both NEC and SIP patients --- p.105 / Chapter 4.1.2.2 --- Differential regulation of Target Molecules in NEC and SIP Patients --- p.106 / Chapter 4.1.2.3 --- "Relative Normalized Expressions of Selected Circulatory Immunoregulatory Protein Molecules in NEC, SIP and Control Neonates" --- p.108 / Chapter 4.1.2.3.1 --- Anti-inflammation --- p.108 / Chapter 4.1.2.3.2 --- Pro-inflammation --- p.109 / Chapter 4.1.2.3.3 --- Cell Growth --- p.110 / Chapter 4.1.2.3.4 --- Wound Healing --- p.110 / Chapter 4.1.2.3.5 --- Angiogenesis --- p.111 / Chapter 4.1.2.3.6 --- "Anti-apoptosis, Cell Adhesion and Extracellular Matrix Organization" --- p.112 / Chapter 4.1.3 --- Further Selection of Novel Target Molecules Based on Statistical Significance and Fold Change of NEC versus SIP --- p.113 / Chapter 4.2 --- Discussion --- p.115 / Chapter CHAPTER FIVE --- Validation of Target Proteins in Plasma of NEC and SIP Patients by Enzyme-linked Immunosorbant Assay --- p.132 / Chapter 5.1 --- Results --- p.133 / Chapter 5.1.1 --- Demographic Data of the Study Group --- p.133 / Chapter 5.1.2 --- "Comparison of Plasma Levels of Target Proteins between NEC, SIP and Respective Controls" --- p.134 / Chapter 5.1.3 --- Longitudinal Study of the Pre- and Post-operative Target Proteins Levels in Plasma --- p.136 / Chapter 5.2 --- Discussion --- p.138 / Chapter CHAPTER SIX --- Investigation on mRNA Expression Levels of Target Immunoregulatory Protein Molecules in Intestinal Tissue and Intestinal Cell Lines --- p.151 / Chapter 6.1 --- Results --- p.152 / Chapter 6.1.1 --- mRNA Expression Levels of Target Molecules in the Diseased Margin of Resected Intestinal Tissues of NEC and SIP patients --- p.152 / Chapter 6.1.2 --- mRNA Expression Levels of Target Molecules in the Macroscopically Normal and Diseased Margin of Resected Intestinal Tissues of NEC and SIP patients --- p.154 / Chapter 6.1.3 --- mRNA Expression Levels of Target Molecules in Human Intestinal Cell Lines upon LPS and PAF Challenge --- p.156 / Chapter 6.1.3.1 --- FHs-74 Int Cell Line --- p.156 / Chapter 6.1.3.2 --- Caco-2 Cell Line --- p.157 / Chapter 6.2 --- Discussion --- p.158 / Chapter CHAPTER SEVEN --- General Discussion --- p.171 / Chapter 7.1 --- Overall Findings --- p.171 / Chapter 7.2 --- Limitations of Study --- p.174 / Chapter 7.3 --- Future Investigations --- p.177 / References --- p.179

O recém-nascido internado na Unidade de Terapia Intensiva (UTI) necessita de cuidados específicos para o seu desenvolvimento saudável, tornando essencial o cuidado prestado pelo enfermeiro. Este estudo teve como objetivos conhecer e compreender a vivência da enfermeira na UTI neonatal e apreender o típico de vivência dessa profissional em ações na UTI neonatal. Optou-se pela abordagem qualitativa, com enfoque da Fenomenologia Social, tendo como base as questões norteadoras: Fale-me do seu dia-a-dia na UTI neonatal. Como você realiza o cuidado direto ao recém-nascido? Além das atividades que você já desenvolve, há alguma outra atividade que gostaria de realizar aqui na UTI neonatal? Identificaram-se categorias concretas do vivido, emergidas dos discursos, as quais foram interpretadas, segundo o referencial de Alfred Schütz. O tipo vivido da enfermeira que atua em UTI neonatal é: aquela que desenvolve ações do dia-a-dia, gerenciando a unidade e a assistência de enfermagem, prestando alguns cuidados diretos ao recém-nascido em situações específicas ou nos cuidados de alta complexidade, atendendo às necessidades dos pais dos recém-nascidos. Algumas enfermeiras, apesar de conviver com vários fatores intervenientes como a inadequada relação funcionário/recém-nascido, a deficiência de equipamentos e materiais, a sobrecarga de trabalho administrativo, a falta de cursos de aprimoramento para aperfeiçoar o cuidado direto ao recém-nascido, a presença de estímulo sonoro na unidade e a dificuldade do trabalho em equipe, sentem-se satisfeitas com sua atuação e com a melhora do recém-nascido. Outras enfermeiras manifestam insatisfação com seu trabalho, sentem-se desvalorizadas e sem autonomia. As enfermeiras têm expectativas quanto ao seu trabalho. Visualizam mudanças, como cursos de aprimoramentos, implantação de protocolos de cuidados, humanização entre a equipe de trabalho e a diminuição do trabalho administrativo. Observou-se a necessidade de adequar a quantidade e a qualidade dos recursos humanos de enfermagem nas UTIs neonatais e de ressignificar as práticas de cuidados das enfermeiras. Ademais, a criação de protocolos, a educação permanente, a qualificação para o manejo dos recursos tecnológicos e a prática de enfermagem baseadas em evidências científicas são fatores que, além de possibilitar aos profissionais que prestem um cuidado de boa qualidade, favorecem a autonomia profissional nas tomadas de decisões / The newborn at NICU (Newborn Intensive Care Unit) needs specific cares to his health development and nurses cares is essential. The goal of this research is to understand the nurse experience at NICU and to comprehend what is typical about these professionals. We choose a qualitative design, according to the Social Phenomenology approach based on the following guiding questions: Tell me about your job at NICU. How do you do the direct care of the newborn? Besides the work you do, would you like to do another tasks at NICU? Based on the nurses discourse, concrete categories were identified which express significant aspects of the experience. This categories were interpreted according to the reference framework of Alfred Schütz. The type experienced by the nurse at NICU was: those who develop day by day tasks, manage the unit and the nurses care, take some direct cares of the newborn in specific situation or in complex cares and take care of newborn parents. Some nurses, in spite of some intervenient factors like inappropriate nurse/newborn relation, deficiency of materials, work administrative overload, lack of training to care of newborn, the noise at NICU, the hardness of work as a team, are satisfied with their work and the getting better of the newborn. Other nurses are not satisfied with their job. They fell their selves disregarded and without autonomy. The nurses have some expectations about their job. They can see possible changes like improvement courses, implementation of care protocols, humanization of the team work and less administrative tasks. We observe the necessity to adapt the amount and quality of nurse team in NICU, and give a new concept of nures´s care. Furthermore, new protocols of care, permanent education, training to technological devices and a evidence based nursing increases the quality of care and promote professional autonomy

Background: Platelet activating factor (PAF) is a phospholipid synthesized by the action of phospholipase A2 and acetyl transferase. PAF possesses a wide range of biological activities. In the lung of the fetus and newborn, PAF binds to its G protein couple receptor to evoke its biological activities via a well-defined signaling pathway. High levels of PAF receptor (PAFr) activity in fetal ovine lung vascular smooth muscle cells (PVSMC) at baseline has previously been demonstrated, a finding that is further perpetuated by conditions of hypoxia similar to fetal lung environment. Additionally in fetal ovine PVSMC, a cross-talk between PAFr-mediated cell signaling and activity of the vasodilator cyclic nucleotides cGMP and cAMP acting via their respective receptors protein kinase (PK) G and PKA has been shown. The interaction of PAF with its receptor has been implicated in the pathogenesis of persistent pulmonary hypertension in the newborn (PPHN) which has a high incidence of hospitalization and death of newborn infants. Successful transition of fetus to newborn life entails a mechanism whereby vasoconstrictors necessary for fetal existence are abrogated in the immediate newborn. Hypothesis: We hypothesize that PPHN results from the failure to down regulate PAFr- mediated activity and /or failure to up-regulate activity of the vasodilators cGMP and cAMP. PPHN is triggered by chronic intrauterine or postnatal hypoxia. Then newborn PVSMC undergo hyperplasia and hypertrophy, which over time, results in irreversible vascular remodeling. Methods: My study aims to employ in vitro models to delineate the consequences of PAF-PAFr mediated pathway in the pharmacological effects of the cAMP-PKA and cGMP-PKG signaling and the involvement of this cross-talk in the pathogenesis of PPHN. I modeled my cell culture studies to mimic the low oxygen environment of fetal lungs (hypoxia), the normal oxygen environment of newborn lungs (normoxia) and high oxygen environment (hyperoxia) to which the newborn lung may be exposed in incidental clinical condition of PPHN. I studied the effect of PAF, a vasoconstrictor, cAMP/cGMP, vasodilators, and other inhibitors of the PAFr pathway on growth of newborn PVSMC, by DNA synthesis, and measured their effects on expression of mitogenic and non-mitogenic proteins. Results: We found that both hypoxia and hyperoxia decreased cell growth even in the presence of PAF which up-regulates cell growth in fetal PVSMC. Also PAF treatment of cells resulted in down regulation of the vasodilator proteins, PKA and PKG. Conclusion: Our data suggests that in the lung of the newborn a high activity of PAF-PAFr mediated activities will worsen the condition of PPHN imposed on the newborn lung by environmental or therapeutic conditions. We can speculate that, in the long run, these findings may translate into the establishment of less toxic protein-based management of PPHN.

This diploma thesis deals with the role of the child nurse in the adaptation of the newborn after delivery.In the theoretical part we devote to the available scientific knowledge focused on the course of pregnancy, the way of giving birth (vaginal and operative), assessment of postnatal adaptation of the newborn, breastfeeding and its importance. The essential part is mapping the role of child nurse in newborn care using the NOC system to evaluate their postnatal adaptation. The Czech and foreign literary sources were used for the theoretical part of the diploma thesis. The first aim of the diploma thesis was a detailed mapping of the role of the child nurse in postnatal adaptation of the newborn after physiological and operative delivery. Two research questions have been selected for its solution. The first research question was, what Apgar values the newborns show after the physiological and operative delivery. The second research question was the success of the first application of the newborn to breastfeeding within 30 minutes after physiological and operative delivery. The second aim of this diploma thesis was to verify the classification of the NOC on the evaluation of the newborn adaptation. For the solution, a research question has been determined, what is the opinion of nurses on the use of the NOC classification system in postnatal adaptation. For the empirical part of the research we have chosen a qualitatively quantitative strategy. Observation, individual semi-structured interviews with nurses and written filling of NOC classification system forms were used for data collection. The first research group was 10 newborns after the physiological - vaginal delivery and 10 newborns after the operative delivery by Caesarean section. The second research group consisted of 2 child nurses working with neonates as part of postnatal adaptation in Hospital Jihlava. Analyzing and interpreting the obtained results, we found out that newborns born by vaginal delivery had an average Apgar score of 8.03 and newborns born by Caesarean section had an average Apgar score of 9.50. The average values of the indicators in the NOC classification system code 0118 The adaptation of the newborn showed slightly poorer results after vaginal deliveries. Two groups of newborns that we followed did not match the generally expected results. Newborns after the Caesarean section are threatened by risk factors, but due to careful nursing care and gentle childbirth, such a risk does not occur and the process of postnatal adaptation can be successful. In the NOC classification system code 1000 Beginning of breastfeeding child showed the indicators at vaginal deliveries, at least 8 feedings per day and infant satisfaction after feeding, better results. In the NOC classification system code 1001 Beginning of breastfeeding mother the average values of breast suction indicators and satisfaction with the breastfeeding process resulted better in favour of neonates born vaginally compared to neonates after Caesarean section. As regards the success of the first feeding of neonates to breastfeeding within 30 minutes after delivery, a clearly superior result was obtained for newborns born vaginally. The conclusions drawn from our research in relation to child breastfeeding by mother confirm the clear benefit of vaginal births for the successful adaptation of newborns. A child nurse undoubtedly plays an important role in the assessment of postnatal adaptation of the newborn. The research of the diploma thesis shows that the classification system NOC is very well sophisticated in the context of a newborn adaptation and it is even detailed in connection with the follow-up and subsequent provision of newborn care. Its full use in current practice in the established care system of particular healthcare facilities is not possible due to insufficient staffing of the department. The existing documentation system does not provide reserves

O recém-nascido internado na Unidade de Terapia Intensiva (UTI) necessita de cuidados específicos para o seu desenvolvimento saudável, tornando essencial o cuidado prestado pelo enfermeiro. Este estudo teve como objetivos conhecer e compreender a vivência da enfermeira na UTI neonatal e apreender o típico de vivência dessa profissional em ações na UTI neonatal. Optou-se pela abordagem qualitativa, com enfoque da Fenomenologia Social, tendo como base as questões norteadoras: Fale-me do seu dia-a-dia na UTI neonatal. Como você realiza o cuidado direto ao recém-nascido? Além das atividades que você já desenvolve, há alguma outra atividade que gostaria de realizar aqui na UTI neonatal? Identificaram-se categorias concretas do vivido, emergidas dos discursos, as quais foram interpretadas, segundo o referencial de Alfred Schütz. O tipo vivido da enfermeira que atua em UTI neonatal é: aquela que desenvolve ações do dia-a-dia, gerenciando a unidade e a assistência de enfermagem, prestando alguns cuidados diretos ao recém-nascido em situações específicas ou nos cuidados de alta complexidade, atendendo às necessidades dos pais dos recém-nascidos. Algumas enfermeiras, apesar de conviver com vários fatores intervenientes como a inadequada relação funcionário/recém-nascido, a deficiência de equipamentos e materiais, a sobrecarga de trabalho administrativo, a falta de cursos de aprimoramento para aperfeiçoar o cuidado direto ao recém-nascido, a presença de estímulo sonoro na unidade e a dificuldade do trabalho em equipe, sentem-se satisfeitas com sua atuação e com a melhora do recém-nascido. Outras enfermeiras manifestam insatisfação com seu trabalho, sentem-se desvalorizadas e sem autonomia. As enfermeiras têm expectativas quanto ao seu trabalho. Visualizam mudanças, como cursos de aprimoramentos, implantação de protocolos de cuidados, humanização entre a equipe de trabalho e a diminuição do trabalho administrativo. Observou-se a necessidade de adequar a quantidade e a qualidade dos recursos humanos de enfermagem nas UTIs neonatais e de ressignificar as práticas de cuidados das enfermeiras. Ademais, a criação de protocolos, a educação permanente, a qualificação para o manejo dos recursos tecnológicos e a prática de enfermagem baseadas em evidências científicas são fatores que, além de possibilitar aos profissionais que prestem um cuidado de boa qualidade, favorecem a autonomia profissional nas tomadas de decisões / The newborn at NICU (Newborn Intensive Care Unit) needs specific cares to his health development and nurses cares is essential. The goal of this research is to understand the nurse experience at NICU and to comprehend what is typical about these professionals. We choose a qualitative design, according to the Social Phenomenology approach based on the following guiding questions: Tell me about your job at NICU. How do you do the direct care of the newborn? Besides the work you do, would you like to do another tasks at NICU? Based on the nurses discourse, concrete categories were identified which express significant aspects of the experience. This categories were interpreted according to the reference framework of Alfred Schütz. The type experienced by the nurse at NICU was: those who develop day by day tasks, manage the unit and the nurses care, take some direct cares of the newborn in specific situation or in complex cares and take care of newborn parents. Some nurses, in spite of some intervenient factors like inappropriate nurse/newborn relation, deficiency of materials, work administrative overload, lack of training to care of newborn, the noise at NICU, the hardness of work as a team, are satisfied with their work and the getting better of the newborn. Other nurses are not satisfied with their job. They fell their selves disregarded and without autonomy. The nurses have some expectations about their job. They can see possible changes like improvement courses, implementation of care protocols, humanization of the team work and less administrative tasks. We observe the necessity to adapt the amount and quality of nurse team in NICU, and give a new concept of nures´s care. Furthermore, new protocols of care, permanent education, training to technological devices and a evidence based nursing increases the quality of care and promote professional autonomy

Made available in DSpace on 2016-03-15T19:41:17Z (GMT). No. of bitstreams: 1 Horacio Bernardo Rosario.pdf: 2513065 bytes, checksum: 21d7ec7d83235895e090241d837335a5 (MD5) Previous issue date: 2012-08-20 / The prevalence rate of live born and stillborn infant twins has been the target of many studies, including in Brazil. However, modifications in people s reproductive style and improvements in labor procedures and better healthcare for newborns show that the knowledge on twinning must be updated over time. To be able to evaluate these modifications better, historical records in hospitals that have regular medical service represent an important frame of reference. In this thesis the records of births of the Centro Obstétrico do Serviço de Ginecologia e de Obstetrícia of the Hospital do Servidor Público Estadual, São Paulo, Brazil, in the period of 1978 to 2009 has been researched, a total of 32 years. In this period, 65,258 labors of stillborn and live born children have been registered. Of this sample, 64,560 were labors of newborn only and 1,396 of double births. Between these, 257 belonged to the genre MM; 270 to FF and 171 to MF. The estimative of the zygosity using the Weinberg method defined that 339 were dizygotic (DZ) and 359 were monozygotic (MZ). The information gathered was stored in a data bank in a computer for future analysis. The SPSS statistical program V 11, 5 using statistical modules, such as correlation analysis, regression analysis, adjusting curves, and comparisons between two groups, analyzed the data. The program Curve Expert V 11,4 was also used for curve fitting. The study of prevalence, maternal age, weight and the Apgar Bulletin allowed the following conclusions: 1. the prevalence varied 0.71 to 1.47% in the 32 years considered. The tendency of prevalence rates for the total of twin births showed a decrease from 1979 to 1993 and an increase around 2005. This distribution is consistent with other Brazilian samples and it can be explained by the variation of maternal age and the use of treatments against infertility. In the last four years there was a decrease in the birth of twins, but this trend did not hold in the years of 2010 and 2011; 2. the prevalence was not evenly distributed between DZ and MZ. Among the first, the distribution was similar to the total twin births. Among the second, there was an increase from 1986 to 2002 in a way that it was higher than that of DZ. In the total sample there was a greater number of MZ. Although not statistically significant this result, 3. the average maternal age of twins was higher than that of the singletons (29,71 years and 28,44 years respectively). This difference is statistically significant according to the literature. The tendency of the distribution of maternal age between twins and singletons is not uniform: there is among the first consistent decrease ranging around 29 years in the first periods to 28 in the last. The variation of maternal age of the twins has a heterogeneous pattern; 4. the average weight of newborns twins was 2,335 g with a tendency to decrease throughout the period. The same trend was observed for singletons. There was also a decrease in gestational age among twins and singletons, it could explain the decline in weight. The trend descending gestational age does not seem to be related to the type of birth since the proportion of these is not changed; 5. the means of the Apgar scores for single births and twins were high in both the first and fifth minutes. The single births had a greater rate and were more stable. The twin births showed consistent increase. 6. the stillbirth among singletons was only less than 1% with a tendency to decrease in recent years and much lower than the national average. Among twins the prevalence is above 3% with increasing tendency. Further studies are needed to lead us to a better enlightenment of the results. / As taxas de prevalência em gêmeos nativivos e natimortos têm merecido muitos estudos, inclusive no Brasil. No entanto, mudanças no estilo reprodutivo das populações e melhorias na assistência ao parto e ao recém-nascido mostram que o conhecimento sobre as concepções gemelares devem ser atualizadas ao longo do tempo. Para melhor avaliar estas mudanças, séries históricas registradas em hospitais com atendimentos regulares \ representam importante referência. Neste trabalho foram levantados os registros dos nascimentos no Centro Obstétrico do Serviço de Ginecologia e de Obstetrícia do Hospital Servidor Público Estadual, São Paulo, Brasil, no período de 1978 a 2009, isto é, 32 anos. Num total de 65.258 partos, entre nativivos e natimortos, 64.560 referem-se a partos de recém-nascidos únicos e 1.396 a nascimentos duplos. Entre estes, 257 eram do gênero MM; 270 FF e 171 MF. A estimativa da zigosidade pelo método de Weinberg definiu que 342 eram Dizigóticos (DZ) e 356 Monozigóticos (MZ). As informações coletadas neste trabalho foram armazenadas em um banco de dados de um microcomputador para posterior análise. Os dados foram analisados pelo do programa estatístico SPSS V 11,5 utilizando-se módulos estatísticos, tais como: análise de correlação e de regressão, ajuste de curvas e comparações entre dois grupos. Foi utilizado também, o programa Curve Expert V 1,4 para o ajuste de curvas. O estudo da prevalência, da idade materna, do peso e do Boletim Apgar permitiu as seguintes conclusões: 1. a prevalência variou de 0,71 a 1,47% nos 32 anos considerados. A tendência das taxas de prevalência para o total dos nascimentos gemelares mostrou declínio entre 1979 e 1993 e logo após aumentando até 2005. Esta distribuição está de acordo com a de outras amostras brasileiras e pode ser explicada pela variação da idade materna e utilização de tratamentos contra infertilidade. No último quadriênio houve diminuição no nascimento de gêmeos, mas essa tendência não se manteve nos anos de 2010 e 2011; 2. a prevalência não se distribuiu uniformemente entre DZ e MZ. Entre os primeiros, a distribuição foi similar ao total dos nascimentos gemelares. Entre os MZ houve incremento entre 1986 a 2002 de maneira a ser maior do que a de DZ. Na amostra total o número de Mz foi maior. No entanto, esta diferença não foi estatisticamente significante, neste resultado. 3. a média da idade materna de gemelares foi maior do que dos únicos (29,71 anos e 28,44 anos, respectivamente). Esta diferença é estatisticamente significante e de acordo com os dados da literatura. A tendência da distribuição da idade materna entre gêmeos e únicos não é uniforme, entre os primeiros há queda consistente variando em torno de 29 anos nos primeiros períodos a 28 nos últimos. Entretanto, a variação da idade materna dos gêmeos tem padrão heterogêneo; 4. a média do peso dos recém-nascidos gemelares foi de 2 335 g com tendência a diminuição ao longo do período. A mesma tendência foi observada para os nascimentos únicos. Observou-se também diminuição da idade gestacional entre gêmeos e únicos, o que poderia explicar o declínio do peso. A tendência decrescente da idade gestacional não parece estar relacionada ao tipo de parto, uma vez que a proporção destes não se modificou; 5. as médias do Boletim Apgar para únicos e gêmeos foram elevadas. A média do Apgar 1 entre os recém-nascidos únicos foi de 7,97 e dos gêmeos foi de 7,00. Com relação ao Apgar 5, a média entre os únicos foi de 9,04 e dos gêmeos foi de 8,33. Entre os primeiros foram maiores e estáveis e entre os segundos demonstram. incremento consistente; 6. a natimortalidade entre únicos foi menor do que 1% com tendência a queda nos últimos anos e bem menor do que a média brasileira. Entre os gêmeos a prevalência fica acima de 3% com tendência crescente. Estudos posteriores serão necessários para compreender melhor alguns dos resultados alcançados.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23781号 / 医博第4827号 / 新制||医||1057(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 石見 拓, 教授 近藤 尚己, 教授 万代 昌紀 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

A meningite bacteriana no período neonatal é uma doença grave, associada à mortalidade elevada e seqüelas em cerca de 12 a 29% dos sobreviventes. Nos recém-nascidos com peso ao nascimento < 2500 g, o risco de adquirir meningite é três vezes superior àqueles com peso >= 2500 g e, entre neonatos de muito baixo peso (< 1500 g), o risco é 17 vezes maior. Objetivo: Geral: descrever o quadro clínico e as complicações da meningite bacteriana em dois grupos de recém-nascidos, considerados de acordo com o peso de nascimento (= 2500 g). Específico: descrever e comparar os agentes etiológicos, a freqüência de sinais e sintomas neurológicos e de complicações, a mortalidade e a duração do tratamento nos dois grupos. Métodos: Estudo observacional de 87 recém-nascidos com meningite bacteriana, admitidos na Unidade de Cuidados Intensivos Neonatais do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, no período de 11 anos (janeiro de 1994 a dezembro de 2004). Os dados foram obtidos através da análise de prontuários. Na análise estatística foram utilizados o teste exato de Fisher e teste não paramétrico de Mann Whitney. Resultados: Foram identificadas bactérias no líquor em 39% dos pacientes, sendo 50% bactérias Gram-positivas e 50% Gram-negativas. A maioria dos neonatos apresentou sinais e sintomas inespecíficos: febre (63,2%), irritabilidade (31%), letargia (26,4%). Os achados neurológicos ocorreram em 35,3% dos casos. As complicações ocorreram em 48,2% dos neonatos, principalmente convulsões (23%), hemorragia intracraniana (14,9%) e hidrocefalia (13,8%) com mortalidade de 11,5 %. Na comparação entre evolução clínica e peso de nascimento observou-se associação entre peso >= 2500 g e convulsão (p=0,047), peso >= 2500 g e fontanela abaulada (p=0,019), bactéria no LCR e complicações (p=0,008) e bactéria no LCR e óbitos (p=0,043). Conclusões: Os agentes etiológicos mais freqüentemente identificados no LCR foram as enterobactérias (41%), seguidas de Streptococcus B (17,5%), Streptococcus não B (17,5%), Staphylococcus aureus (11,7%), Neisseria meningitidis (8,8%) e Enterococcus faecalis (3,0%), não havendo diferença entre tipo de bactérias e peso de nascimento. Os sinais e sintomas predominantes foram inespecíficos, com achados neurológicos em 35% dos casos. A freqüência maior de sintomas neurológicos nos recém-nascidos com peso >= 2500 g, sugere maior grau de maturidade do sistema nervoso central nestas crianças. Embora a mortalidade tenha sido inferior à observada em estudos anteriores no mesmo Serviço, a freqüência de complicações foi alta, independentemente do peso de nascimento. A presença de bactéria no LCR associou-se à maior freqüência de convulsões e mortalidade. A necessidade de manutenção do tratamento por tempo mais prolongado nos recém-nascidos de baixo peso sugere maior gravidade da doença neste grupo de neonatos. / Bacterial meningitis in the neonatal period is a severe disease, associated to elevated mortality and sequelae in around 12 to 29% of the survivors. Newborns whose birth weight is < 2,500g have a 3-fold increase in the risk of acquiring meningitis when compared to those whose weight is >= 2,500; among those with very low birth weight (< 1,500g), the risk increases 17-fold. Objectives: General: to describe the clinical picture and the complications of bacterial meningitis in two groups of newborns, considered according to birth weight (< 2,500g or >= 2,500g). Specific: to describe and compare the etiological agents, the frequency of neurological signs and symptoms and complications, mortality rate and duration of treatment in both groups. Methods: Observational study of 87 newborns with bacterial meningitis, admitted at the Neonatal Intensive Care Unit (NICU) of Instituto da Criança of Hospital das Clínicas of the University of São Paulo School of Medicine, during an 11-year period (January 1994 to December 2004). The data were obtained through the analysis of hospital files. Statistical analysis was carried out with Fisher\'s exact test and the non-parametric Mann Whitney test. Results: Bacteria were identified in the cerebrospinal fluid (CSF) of 39% of the patients, with 50% of them being Gram-positive and 50%, Gram-negative. Most neonates presented unspecific signs and symptoms: fever (63.2%), irritability (31%), and lethargy (26.4%). The neurological findings occurred in 35.3% of the cases. Complications occurred in 48.2% of the neonates, and were mainly seizures (23%), intracranial hemorrhage (14.9%) and hydrocephalus (13.8%) with a mortality rate of 11.5%. At the comparison between clinical evolution and birth weight, associations between weight >= 2,500g and seizures (p=0.047), weight >= 2,500g and concave fontanel (p=0.019), bacteria in the CSF and complications (p=0.008) and bacteria in the CSF and death (p=0.043) were observed. Conclusions: The etiological agents most often identified in the CSF were enterobacteria (41%), followed by B Streptococcus (17.5%), non-B Streptococcus (17.5%), Staphylococcus aureus (11.7%), Neisseria meningitidis (8.8%) and Enterococcus faecalis(3.0%), with no statistical difference between the type of bacteria and birth weight. The predominant signs and symptoms were unspecific, with neurological findings in 35% of the cases. The higher frequency of neurological signs and symptoms in newborns with birth weight >= 2,500g suggest a higher degree of central nervous system maturity in these infants. Although the mortality was lower than that observed in previous studies at the same Service, the frequency of complications was high, regardless of birth weight. The presence of bacteria in the CSF was associated to a higher frequency of seizures and mortality. The need for prolonged treatment in newborns with low birth weight suggests higher disease severity in this group of neonates.

A meningite bacteriana no período neonatal é uma doença grave, associada à mortalidade elevada e seqüelas em cerca de 12 a 29% dos sobreviventes. Nos recém-nascidos com peso ao nascimento < 2500 g, o risco de adquirir meningite é três vezes superior àqueles com peso >= 2500 g e, entre neonatos de muito baixo peso (< 1500 g), o risco é 17 vezes maior. Objetivo: Geral: descrever o quadro clínico e as complicações da meningite bacteriana em dois grupos de recém-nascidos, considerados de acordo com o peso de nascimento (= 2500 g). Específico: descrever e comparar os agentes etiológicos, a freqüência de sinais e sintomas neurológicos e de complicações, a mortalidade e a duração do tratamento nos dois grupos. Métodos: Estudo observacional de 87 recém-nascidos com meningite bacteriana, admitidos na Unidade de Cuidados Intensivos Neonatais do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, no período de 11 anos (janeiro de 1994 a dezembro de 2004). Os dados foram obtidos através da análise de prontuários. Na análise estatística foram utilizados o teste exato de Fisher e teste não paramétrico de Mann Whitney. Resultados: Foram identificadas bactérias no líquor em 39% dos pacientes, sendo 50% bactérias Gram-positivas e 50% Gram-negativas. A maioria dos neonatos apresentou sinais e sintomas inespecíficos: febre (63,2%), irritabilidade (31%), letargia (26,4%). Os achados neurológicos ocorreram em 35,3% dos casos. As complicações ocorreram em 48,2% dos neonatos, principalmente convulsões (23%), hemorragia intracraniana (14,9%) e hidrocefalia (13,8%) com mortalidade de 11,5 %. Na comparação entre evolução clínica e peso de nascimento observou-se associação entre peso >= 2500 g e convulsão (p=0,047), peso >= 2500 g e fontanela abaulada (p=0,019), bactéria no LCR e complicações (p=0,008) e bactéria no LCR e óbitos (p=0,043). Conclusões: Os agentes etiológicos mais freqüentemente identificados no LCR foram as enterobactérias (41%), seguidas de Streptococcus B (17,5%), Streptococcus não B (17,5%), Staphylococcus aureus (11,7%), Neisseria meningitidis (8,8%) e Enterococcus faecalis (3,0%), não havendo diferença entre tipo de bactérias e peso de nascimento. Os sinais e sintomas predominantes foram inespecíficos, com achados neurológicos em 35% dos casos. A freqüência maior de sintomas neurológicos nos recém-nascidos com peso >= 2500 g, sugere maior grau de maturidade do sistema nervoso central nestas crianças. Embora a mortalidade tenha sido inferior à observada em estudos anteriores no mesmo Serviço, a freqüência de complicações foi alta, independentemente do peso de nascimento. A presença de bactéria no LCR associou-se à maior freqüência de convulsões e mortalidade. A necessidade de manutenção do tratamento por tempo mais prolongado nos recém-nascidos de baixo peso sugere maior gravidade da doença neste grupo de neonatos. / Bacterial meningitis in the neonatal period is a severe disease, associated to elevated mortality and sequelae in around 12 to 29% of the survivors. Newborns whose birth weight is < 2,500g have a 3-fold increase in the risk of acquiring meningitis when compared to those whose weight is >= 2,500; among those with very low birth weight (< 1,500g), the risk increases 17-fold. Objectives: General: to describe the clinical picture and the complications of bacterial meningitis in two groups of newborns, considered according to birth weight (< 2,500g or >= 2,500g). Specific: to describe and compare the etiological agents, the frequency of neurological signs and symptoms and complications, mortality rate and duration of treatment in both groups. Methods: Observational study of 87 newborns with bacterial meningitis, admitted at the Neonatal Intensive Care Unit (NICU) of Instituto da Criança of Hospital das Clínicas of the University of São Paulo School of Medicine, during an 11-year period (January 1994 to December 2004). The data were obtained through the analysis of hospital files. Statistical analysis was carried out with Fisher\'s exact test and the non-parametric Mann Whitney test. Results: Bacteria were identified in the cerebrospinal fluid (CSF) of 39% of the patients, with 50% of them being Gram-positive and 50%, Gram-negative. Most neonates presented unspecific signs and symptoms: fever (63.2%), irritability (31%), and lethargy (26.4%). The neurological findings occurred in 35.3% of the cases. Complications occurred in 48.2% of the neonates, and were mainly seizures (23%), intracranial hemorrhage (14.9%) and hydrocephalus (13.8%) with a mortality rate of 11.5%. At the comparison between clinical evolution and birth weight, associations between weight >= 2,500g and seizures (p=0.047), weight >= 2,500g and concave fontanel (p=0.019), bacteria in the CSF and complications (p=0.008) and bacteria in the CSF and death (p=0.043) were observed. Conclusions: The etiological agents most often identified in the CSF were enterobacteria (41%), followed by B Streptococcus (17.5%), non-B Streptococcus (17.5%), Staphylococcus aureus (11.7%), Neisseria meningitidis (8.8%) and Enterococcus faecalis(3.0%), with no statistical difference between the type of bacteria and birth weight. The predominant signs and symptoms were unspecific, with neurological findings in 35% of the cases. The higher frequency of neurological signs and symptoms in newborns with birth weight >= 2,500g suggest a higher degree of central nervous system maturity in these infants. Although the mortality was lower than that observed in previous studies at the same Service, the frequency of complications was high, regardless of birth weight. The presence of bacteria in the CSF was associated to a higher frequency of seizures and mortality. The need for prolonged treatment in newborns with low birth weight suggests higher disease severity in this group of neonates.

Indiana University-Purdue University Indianapolis (IUPUI) / Objectives: To determine (1) whether prescribed and delivered energy and protein intakes during the first two weeks of life met Ziegler’s estimated requirements for Very Low Birth Weight (VLBW) infants, (2) if actual energy during the first week of life correlated with time to regain birth weight and reach full enteral nutrition (EN) defined as 100 kcal/kg/day, (3) if growth velocity from time to reach full EN to 36 weeks’ postmenstrual age (PMA) met Ziegler’s estimated fetal growth velocity (16 g/kg/day), and (4) growth outcomes at 36 weeks’ PMA. Study design: Observational study of feeding, early nutrition and early growth of 40 VLBW infants ≤ 30 weeks GA at birth in three newborn intensive care units NICUs. Results: During the first week of life, the percentages of prescribed and delivered energy (69% [65 kcal/kg/day]) and protein (89% [3.1 g/kg/day]) were significantly less than theoretical estimated requirements. Delivered intakes were 15% less than prescribed because of numerous interruptions in delivery and medical complications. During the second week, the delivered intakes of energy (90% [86 kcal/kg/day]) and protein (102% [3.5 g/kg/day]) improved although the differences between prescribed and delivered were consistently 15%. Energy but not protein intake during the first week was significantly related to time to reach full EN. Neither energy nor protein intake significantly correlated with days to return to birth weight. The average growth velocity from the age that full EN was attained to 36 weeks’ PMA (15 g/kg/day) was significantly less than the theoretical estimated fetal growth velocity (16 g/kg/day) (p<0.03). A difference of 1 g/kg/day represents a total deficit of 42 - 54 grams over the course of a month. At 36 weeks’ PMA, 53% of the VLBW infants had extrauterine growth restriction, or EUGR (<10th percentile) on the Fenton growth grid and 34% had EUGR on the Lubchenco growth grid. Conclusions: The delivered nutrient intakes were consistently less than 15% of the prescribed intakes. Growth velocity between the age when full EN was achieved and 36 weeks’ PMA was 6.7% lower than Ziegler’s estimate. One-third to one-half of the infants have EUGR at 36 weeks’ PMA.