Na atuação multiprofissional em unidade neonatal, tem-se observado a dificuldade em sistematizar uma avaliação objetiva do comportamento de sucção do bebê e seu desempenho na transição da alimentação láctea, por sonda, para a via oral. Assim, o presente estudo tem por objetivo elaborar e validar o conteúdo e a aparência de um instrumento de avaliação da prontidão do bebê prematuro em iniciar a transição da alimentação gástrica para via oral. Trata-se de estudo metodológico, para o qual elaborou-se o referido instrumento e respectivo guia instrucional, tendo por base a revisão de literatura e a experiência profissional da pesquisadora, que atribuiu escores de 0 a 2 para cada sinal clínico e desempenho do prematuro a ser avaliado. Para validação do instrumento e guia instrucional, estabeleceu-se grau de concordância mínimo de 85%, participando como juízes, fonoaudiólogos com ampla experiência na área de Neonatologia Atuaram 15 fonoaudiólogos na primeira etapa e 14 na segunda, ocasião em que se atingiu a concordância aceitável nos itens do instrumento de avaliação e respectivas definições operacionais contidas no guia instrucional (idade corrigida, estado de consciência, postura global, tônus global, postura dos lábios, postura da língua, reflexo de procura, reflexo de sucção, reflexo de mordida, reflexo de vômito, movimentação da língua, canolamento de língua, movimentação da mandíbula, força de sucção, sucções por pausa, manutenção do ritmo de sucção por pausa, manutenção do estado alerta e sinais de estresse). / Considering the multiprofessional performance in a neonatal unit, we found difficulties in systematizing an objective evaluation of infant sucking and performance in the transition from gavage to oral feeding. Therefore, this study aimed at elaborating and validating the content and appearance of an instrument for the evaluation of preterm infant promptness to begin the transition from gastric to oral feeding. In this methodological study, the author elaborated an instrument and its respective instructional guide based on a literature review and her professional experience, assigning scores from 0 to 2 to each clinical sign and performance of the premature infant. In order to validate the instrument and instructional guide, a 85% minimum level of agreement was established. Oral therapist participated as peers in the validation of the instrument and instructional guide. 15 of them participated in the first phase and 14 in the second one, when the acceptable level of agreement was achieved regarding the items of the evaluation instrument and the operational definitions specified in the instructional guide (corrected age, state of awareness, global posture, global tonus, lips posture, tongue posture, rooting reflex, sucking reflex, biting reflex, gag reflex, tongue movement, jaw movement, sucking power, sucking and pause, maintenance of the rhythm of sucking and pause, maintenance of alert state and stress signs).

O presente estudo teve os seguintes objetivos: a) examinar os indicadores de desenvolvimento cognitivo, motor, de linguagem e sócio emocional de crianças nascidas pré-termo de alto risco neonatal em comparação a crianças nascidas a termo sem condição de vulnerabilidade biológica no início do desenvolvimento, até os 15 primeiros meses de idade corrigida para prematuridade (ICo); b) examinar os indicadores de desenvolvimento especificamente no grupo de prematuros, comparando os respectivos sub-grupos de acordo com: nível de prematuridade (extremo e muito prematuro), presença ou ausência de hemorragia intracraniana e presença ou ausência da condição gemelaridade; c) identificar as variáveis preditoras do desenvolvimento das crianças nascidas pré-termo, considerando-se variáveis neonatais clínicas e psicossociais. Participaram do estudo 133 crianças, de ambos os sexos, sendo 54 nascidas pré-termo (PT) e 79 nascidas a termo (AT), e suas respectivas mães, no primeiro ano de idade, que nasceram no Complexo HCFMRP-USP. O projeto foi aprovado pelo Comitê de Ética em Pesquisa do HCFMRP-USP, Processo HC n° 8244/2016. Na coleta de dados, o desenvolvimento das crianças foi avaliado pelas Escalas Bayley-III (cognitiva, motora, de linguagem e sócio emocional). Além disso, foram aplicados questionários de caracterização da amostra e a Escala ABEP - Associação Brasileira de Empresas de Pesquisa (2014). Os indicadores clínicos neonatais foram analisados a partir dos prontuários médicos das crianças. Na análise de dados, inicialmente, foi processada a análise estatística descritiva das características da amostra e dos indicadores de desenvolvimento. Em seguida, foi realizada a análise estatística inferencial de comparação entre grupos por meio dos testes t-independente de Student (variáveis contínuas) ou Qui-Quadrado (variáveis categóricas). Utilizou-se os testes MANOVA e ANOVA para examinar as potenciais diferenças entre os grupos, relacionadas aos indicadores de desenvolvimento das crianças controlando-se as variáveis idade da criança e nível sócio-econômico. Além disso, foram realizadas análises de regressão linear múltiplas com a amostra de crianças nascidas pré-termo, examinando-se as interações entre as variáveis preditoras (tempo de internação na UTIN, tempo de internação total e tempo de uso do Continuous Positive Airway Pressure - CPAP), as variáveis preditas nos modelos foram os escores do desenvolvimento (cognitivo, linguagem, motor e sócio emocional), na fase de 6-8 e 12-15 meses ICo. Por fim, foi realizada a análise de comparação intra-grupo (6-8 vs 12-15 meses ICo) por meio dos testes de t-pareado, para variáveis contínuas (escores da Bayley-III) e do teste de Wilcoxon para variáveis categóricas (classificações da Bayley-III). Os dados foram analisados pelo Statistical Package for Social Sciences (SPSS, versão 25.0, Chicago, Il, USA). O nível de significância adotado no estudo foi de p <= 0,05. Os resultados mostraram que as crianças do grupo PT, tanto na fase de 6-8, quanto na fase de 12-15 meses ICo, apresentaram menores escores médios, em todos os indicadores avaliados pelas Escalas Bayley-III (cognitivo, de linguagem, motor e sócio emocional), em comparação com o grupo AT. Apesar de haver diferenças entre os grupos, a maioria das crianças nascidas prematuras estavam com o desenvolvimento na faixa de normalidade pelas normas das escalas. Esses achados foram independentes do nível de prematuridade, da presença de hemorragia intracraniana ou história de gemelaridade. Verificou-se ainda que os escores médios dos indicadores de desenvolvimento dos dois grupos (PT e AT) aos 12-15 meses ICo não foram maiores do que aos 6-8 meses ICo. No entanto, ainda que não tenha sido observada uma evolução no desenvolvimento, as crianças de ambos os grupos estavam com o desenvolvimento na faixa de normalidade pelas normas das escalas Bayley-III. Por fim, o tempo de internação na UTIN e o tempo de uso do CPAP foram os principais fatores de risco preditores para problemas no desenvolvimento cognitivo, motor, de linguagem e sócio emocional das crianças nascidas pré-termo / The present study had the following objectives: a) to examine the indicators of cognitive, motor, language and socio emotional development of neonatal high-risk preterm infants in comparison to infants born full-term without biological vulnerability condition at the beginning of the development, until the first 15 months of corrected age for prematurity (Co); b) to examine the developmental indicators specifically in the preterm group, comparing the respective subgroups according to: prematurity level (extreme and very premature), presence of intracranial hemorrhage and condition of being a twin; c) to identify the predictive variables of the development of preterm infants, considering neonatal clinical and psychosocial variables. The study consisted of 133 children of both sexes, being 54 born preterm (PT) and 79 born full-term (FT), and their respective mothers, in the first 15 months Co, born in the HCFMRP-USP Complex. The project was approved by the Research Ethics Committee of HCFMRP-USP. In data collection, the development of the infants was evaluated by the Bayley-III Scales (cognitive, motor, language and socio emotional). In addition, sample characterization questionnaires and the ABEP - Brazilian Association of Research Companies (2014) scale were applied. The neonatal clinical indicators were analyzed based on the medical records. In the data analysis, the descriptive statistical analysis of sample characteristics and development indicators was performed. Then, the inference statistical analysis of the comparison between groups was done by Student\'s independent t-test (continuous variables) or Chi-Square (categorical variables). The MANOVA and ANOVA tests were used to examine the potential differences between the groups, related to the developmental indicators of the children, controlling the age of the child and socio-economic level. In addition, multiple linear regression analyzes were performed with the preterm infants sample, examining the interactions among the predictor variables (length of stay in the NICU, length of stay in the hospital and time of use of the Continuous Positive Airway Pressure - CPAP), the predicted variables in the models were the development scores (cognitive, language, motor and socio emotional), in the 6-8 and 12-15 months Co phases. Finally, the intra-group comparison analysis (6-8 vs. 12-15 months ICo) was performed through t-paired tests for continuous variables (Bayley-III scores) and the Wilcoxon test for categorical variables (Bayley-III ratings). The data were analyzed by the Statistical Package for Social Sciences (SPSS, version 25.0, Chicago, Il, USA). The level of significance adopted in the study was p <= 0.05. The results showed that infants in the PT group, both in the 6-8 and in the 12-15 months Co phases, presented significantly lower mean scores in all indicators assessed by the Bayley-III Scales (cognitive, language, motor and socio emotional) compared to the FT group. Although there were differences between groups, the majority of the infants born preterm were developing in the normal range based on the norms of the scales. These findings were independent of the level of prematurity, the presence of intracranial hemorrhage or the condition of being a twin. It was also verified that the mean scores of the development indicators of the two groups (PT and FT) at 12-15 months Co were not higher than at 6-8 months Co. However, although developmental progress was not observed, the children of both groups were developing in the normal range based on the norms of the Bayley-III scales. Finally, length of stay in the NICU and duration of CPAP use were the main predictor risk factors for cognitive, motor, language and socio emotional problems in preterm infants

Introduction: Preterm birth is increasing worldwide and is a major cause of neonatal death. Survivors are at increased risk of neurodisability, cognitive, social and psychiatric disorders in later life. Alterations to the white matter can be assessed using diffusion tensor imaging (DTI) MRI and are associated with poor neurodevelopmental outcome. The pathogenesis of white matter injury is multifactorial and several clinical risk and resilience factors have been identified. DNA methylation (DNAm) is an epigenetic process which links stressful early life experience to later life disease and is associated with normal brain development, neuronal processes and neurological disease. Several studies have shown DNAm is altered by the perinatal environment, however its role in preterm white mater injury is yet to be investigated. Aims: 1. To examine the relationship between preterm birth and white matter integrity 2. To investigate the effect of neuroprotective treatments and deleterious clinical states on white matter integrity in preterm infants 3. To assess the best DTI method of quantifying white matter integrity in a neonatal population 4. To investigate the effect of preterm birth on DNA methylation and 5. To determine the clinical and imaging factors that contribute to the variance in DNA Methylation caused by preterm birth Methods: DTI data was acquired from preterm infants (< 32 weeks' gestation or < 1500 grams at birth) at term equivalent age (TEA) and term controls (> 37 weeks' gestation at birth). Region-of-interests (ROI) and tract-averaged methods of DTI analysis were performed to obtain measurements of fractional anisotropy (FA) and mean diffusivity (MD) in the genu of corpus callosum, posterior limb of internal capsule and centrum semiovale. Clinical data was collected for all infants and the effect of prematurity, neuroprotective agents and clinical risk factors on white matter integrity were analysed. 8 major white matter tracts were segmented using probabilistic neighbourhood tractography (PNT), a tract-averaged technique which also allowed the calculation of tract shape. The two DTI techniques were compared to evaluate agreement between results. DNA was collected from preterm infants and term controls at TEA, and a genome-wide analysis of DNAm was performed. DTI parameters from probabilistic neighborhood tractography (PNT) methodology and clinical risk and resilience factors were used to inform a principal components analysis to investigate the contribution of white matter integrity and clinical variables to variance in DNAm. Results: FA and MD were significantly affected by preterm birth on ROI analysis. In addition, DTI parameters were affected by clinical factors that included antenatal magnesium sulphate, histological chorioamnionitis and bronchopulmonary dysplasia. Evaluation of DTI methodology revealed good accuracy in repeated ROI measurements but limited agreement with tract-averaged values. Differential methylation was found within 25 gene bodies and 58 promoters of protein-coding genes in preterm infants, compared with controls. 10 of these genes have a documented association with neural function or neurological disease. Differences detected in the array were validated with pyrosequencing which captured additional differentially methylated CpGs. Ninety-five percent of the variance in DNAm in preterm infants was explained by 23 principal components (PC); corticospinal tract shape associated with 6th PC, and gender and early nutritional exposure associated with the 7th PC. Conclusions: Preterm birth is associated with alterations in white matter integrity which is modifiable by clinical risk factors and neuroprotective agents. ROI analysis may not provide sufficient representation of white matter tracts in their entirety. Prematurity is related to alterations in the methylome at sites that influence neural development and function. Differential methylation analysis has identified several promising candidate genes for future work and contributed to the understanding of the pathogenesis of preterm brain injury.

A dor encontra-se inerente aos procedimentos de tratamento intensivo dos recém-nascidos pré-termo em Unidade de Terapia Intensiva Neonatal. As experiências precoces e repetidas de dor podem ter efeitos a longo prazo para os recém-nascidos vulneráveis. A Academia Americana de Pediatria e a Sociedade Pediátrica Canadense recomendam o uso da solução de sacarose como rotina para alívio da dor em Unidade de Terapia Intensiva Neonatal, durante os procedimentos invasivos e dolorosos. O presente estudo teve por objetivo avaliar as reações de dor de neonatos pré-termo durante procedimento de coleta de sangue, analisando o momento da punção, assim como os efeitos do manuseio dos neonatos para a anti-sepsia e o curativo e avaliar a eficácia da intervenção com solução de sacarose a 25% no alívio da dor administrando-a em dose única de 0,5ml/Kg. Trinta e três neonatos foram distribuídos randomicamente em dois grupos: Grupo Sacarose (n=17) e Grupo Água (n=16). Os neonatos foram avaliados durante dois dias consecutivos. Na primeira avaliação, os neonatos de ambos os grupos não receberam nenhuma substância antes do procedimento doloroso. Na segunda avaliação, o Grupo Sacarose recebeu sacarose oral e o Grupo Água recebeu água estéril, dois minutos antes do procedimento invasivo e doloroso de punção para coleta de sangue. Cada avaliação foi dividida em cinco fases: Linha de Base, Preparação para Punção (anti-sepsia), Punção, Recuperação com Manuseio (curativo) e Recuperação sem Manuseio. O indicador de dor foi avaliado pela atividade facial, que foi mensurada pelo Neonatal Facial Coding System. O nível de ativação dos neonatos foi medido pelo estado de vigília e sono e pela freqüência cardíaca. A análise entre grupos e intra-grupo dos dados revelou que no primeiro dia de avaliação os neonatos anteciparam a reação ao estímulo doloroso de punção, apresentando elevação significativa dos indicadores atividade facial, estado de vigília e sono e freqüência cardíaca avaliados na Preparação para Punção. Ambos os grupos mostraram alta reatividade comportamental e fisiológica na fase de Punção, em comparação à Linha de Base. Durante a recuperação, o indicador fisiológico de freqüência cardíaca continuou elevado. No segundo dia de avaliação os neonatos que receberam 0,5ml/Kg de solução de sacarose a 25% apresentaram menores escores de atividade facial, indicativo de menos dor, em comparação aos neonatos que receberam água estéril, antes, durante e após o procedimento de punção para coleta de sangue. Entretanto, o indicador fisiológico de freqüência cardíaca não apresentou diferença significativa entre os grupos. Conclui-se que a dose de 0,5ml/Kg de solução de sacarose a 25%, recomendada para a administração da substância em doses repetidas, foi eficaz no alívio de dor, avaliada por meio da redução de indicadores comportamentais. Entretanto, o indicador fisiológico continuou elevado, sugerindo a necessidade de outras medidas de conforto associadas à sacarose, com a finalidade de atenuação do estado de ativação e irritabilidade do sistema nervoso central. / Pain is inherent to the intensive treatment procedures offered to preterm neonates in Neonatal Intensive Care Units. The early and repeated experiences of pain may have a long-term effects for the vulnerable neonates. The American Academy of Pediatrics and the Canadian Pediatric Society recommend using a sucrose solution for pain relief in NICU during invasive and painful procedures. The present study had the purpose to assess the pain reactions of preterm neonates during a procedure for blood collection, evaluating the moment of puncture as well as the effects of handling the neonates for antisepsis and for bandages, and evaluating the efficacy of the intervention with the sucrose solution at 25% for pain relief by administering a single dose of 0.5 ml/Kg. Thirty-three neonates were randomly assigned to two groups: Sucrose Group (n=17) and Water Group (n=16). The neonates were evaluated during two consecutive days. In the first assessment, the neonates from both groups did not receive the solution before the painful procedure. In the second assessment, the Sucrose Group received oral sucrose and the Water Group received sterile water, two minutes before the invasive painful procedure of puncture for blood collection. Each evaluation was divided into five phases: Baseline, Preparation for Puncture (antisepsis), Puncture, Recovery with Handling (bandage), and Recovery without Handling. The indicators of pain were evaluated by the facial activity, measured by the Neonatal Facial Coding System. The level of activation of the neonates was measured by their sleep-awake state and heart rate. The between and within-group data analysis revealed that, on the first day of evaluation, the neonates anticipated their reaction to the painful puncture stimulus, and showed a significant increase in the behavioral indicators of facial activity, sleep-awake state, and heart rate evaluated at the Preparation for Puncture. Both groups showed a high behavioral and physiological reactivity in the Puncture phase, in comparison to the Baseline. During recovery, the physiological indicator of heart rate continued high. In the second day of evaluation, the neonates who received 0.5 ml/Kg of the sucrose solution at 25% showed lower scores of facial activity, which indicates they experienced less pain in comparison to the neonates who received sterile water before, during, and after the procedure of puncture for blood collection. However, there were no significant differences in terms of the physiological indicator of heart rate. It is concluded that the dose of 0.5 ml/kg of sucrose solution at 25%, recommended for the administration in repeated doses, was efficient for pain relief, evaluated by means of the reduction of behavioral indicators. However, the physiological indicator remained high, which suggests there is a need for other comfort manegement associated to sucrose, with the aim to diminish the state of activation and irritability of the central nervous system.

Although inflammation is a crucial mechanism in response to injury and pathogen clearance, inappropriate or excessive induction of the inflammatory response in pregnancy can cause initiation of the labour cascade and subsequent preterm delivery. Host Defence Peptides (HDPs) have important anti-microbial properties but are also implicated as multifunctional modulators of immunity and infection. They are predominantly secreted by mucosal epithelial cells and released by leukocytes. The specific HDPs that are the focus of this thesis are Human beta-defensin 3 (hBD3) and Human Cathelicidin (hCAP-18/LL-37). The immunomodulatory effect of HDPs in reproductive tissues in response to infection/inflammation has not been well studied. In a pregnant state, the hypothesis of this thesis is that HDPs have a dual role in preventing ascending infection, but also preventing an exacerbated inflammatory response that can cause preterm birth by initiation of the labour cascade. To explore this I determine whether bacterial stimuli can regulate HDPs expression in pregnancy tissues. I also explore what interactions HDPs have on the production/induction of important cytokines that are vital to the inflammatory response. With the aid of HDP knockout mice, the role of these peptides in infection/inflammation and continuation of pregnancy is investigated in a mouse-model of induced preterm-labour. To understand how ascending infection might be controlled by HDPs in pregnancy, I explore how HDPs regulate commensal and pathogenic bacteria. This is achieved by interrogating the maternal microbiome at mucosal sites in HDP knockout animals, utilising the bacterial 16S rRNA gene and next generation sequencing. Results Placental explants respond to Lipopolysaccharide (LPS) challenge by increasing production of pro-inflammatory cytokines. LL-37 but not hBD3 peptide was able to modulate this inflammation by inhibiting the release of these pro-inflammatory cytokines. To establish whether HDPs are critical in the continuation of pregnancy I use a LPS induced mouse–model of preterm labour in animals lacking the genes for the HDPs, Defb14 (Defb14-/-), or Camp (Camp-/-). Intrauterine injection of LPS induced preterm labour in wildtype mice. However, the Defb14-/- and Camp-/- mice do not have an increased rate of preterm labour. Key inflammatory mediators are increased in response to LPS-induced PTL. Camp-/- animals have a similar inflammatory response to wildtype mice when given LPS during pregnancy. To understand how ascending infection might be controlled by HDPs, I interrogated the maternal microbiome at mucosal sites in HDP knockout animals, utilising the bacterial 16S rRNA gene. I established a workflow for 16S rRNA gene sequencing on next-generation sequencing platforms and a bioinformatic pipeline for data analysis. Using this approach I was able to show the mucosal microbiome of Camp-/- animals were significantly different to that of wildtype controls, showing increased diversity in the microbes present. In murine pregnancy, there were very little global cumulative or progressive shifts in bacteria, with the exception of Candidatus arthromitus, which significantly increases with gestation compared to non-pregnancy This thesis has demonstrated that Host Defence Peptides are expressed in pregnancy tissues and have anti-inflammatory properties in response to bacterial stimuli. It is not clear whether the HDPs, hBD3 and LL-37 are fundamental to the immune defence in pregnancy by preventing excessive inflammation, Although, I have shown LL-37 may have a role in modulation of the maternal microbiota.

Orientadores: Paulo César Giraldo, Ana Katherine da Silveira Gonçalves / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-11-07T13:39:58Z (GMT). No. of bitstreams: 1 Araujo_EdilsonDiasde_D.pdf: 2801870 bytes, checksum: 056091a8cfb4211f4402aa3462d60140 (MD5) Previous issue date: 2010 / Resumo: As infecções urogenitais (IUG) são muito prevalentes durante a gestação e são reconhecidamente uma das principais causa de trabalho de parto prematuro. Entretanto, a prevalência de IUG no período intraparto é pouco conhecida. Diversas variáveis podem alterar a concentração das imunoglobulinas no colostro. A prematuridade e as infecções urogenitais têm sido estudadas como um destes fatores. Objetivos: Avaliar a prevalência de infecções urogenitais em gestantes durante o trabalho de parto pré-termo e a termo; quantificar os níveis de IgA secretória no colostro de puérperas de parto pré-termo e a termo com e sem infecção urogenital e correlacionar os níveis de IgA secretória nos colostros das puérperas com a presença de infecções urogenitais. Metodologia: No per iodo de janei ro a junho de 2009, 94 gestantes em trabalho de parto, atendidas na Maternidade Escola Januário Cicco (MEJC) da Universidade Federal do Rio Grande do Norte (UFRN), foram alocadas em dois grupos, 49 gestantes em trabalho de parto pré-termo e 45 gestantes em trabalho de parto a termo, foram convidadas a participar do estudo. Para uma melhor homogeneização dos resultados, apenas 34 mães de recém nascidos pré-termo (RNPT) e 38 mães de recém nascidos a termo (RNT), totalizando 72 mães que expressaram colostro no segundo dia de puerpério tiveram seus níveis de IgAs quantificados mediante a utilização de ensaio imunoenzimático (ELISA). Todas as gestantes assinaram o Termo de Consentimento Livre e Esclarecido e passaram por exame ginecológico, quando foi coletado material urinário, vaginal e perianal para estudo microbiológico. Resultados: Nos 94 casos estudados, a prevalência de infecções urogeni tais nas gestantes de parto pré-termo foi d 49,0% e nas gestantes de parto a termo de 53,3% (p=0,8300). Considerando-se os casos de infecções urogenitais, nas gestantes de parto pré-termo e a termo, encontrou-se ITU em 36,7% e 22,2%, candidíase vaginal em 20,4% e 28,9%, vaginose bacteriana em 34,7% e 28,9% e estreptococos do grupo B em 6,1 e 15,6%, respectivamente. Entre as 72 puérperas de recém nascidos de par to prétermo (34) e a termo (38) estudadas, a prevalência de infecções urogenitais nas gestantes de parto pré-termo foi de 50,0% e nas a termo de 52,6%. Considerando-s os casos de infecções urogenitais específicas, nas gestantes de parto pré-termo e a termo, encontraram-se infecção do trato urinário ( ITU) em 32,4% e 15,8%, candidíase vaginal em 17,6% e 26,3%, vaginose bacteriana em 38,2% e 31,6% e estreptococos do grupo B em 5,9% e 15,8%, respectivamente. As concentrações de IgAs foram significativamente mais elevadas no grupo de puérperas de RNPT (1051,3 mg/dL) que no grupo de puérperas de RNT (396,3 mg/dL). Conclusões: Os níveis de IgAs no colostro de mães de RN pré-termo foram significantemente mais elevados que os encontrados em mães de RN a termo. Entretanto apesar da elevada prevalência de diferentes infecções genitais intrapartais, estas não tiveram influência sobre os níveis médios de IgAs, sugerindo que este aumento observado no colostro de mães de RN pré termo esteja relacionado a fatores adaptativos da prematuridade e não a presença das infecções / Abstract: Urogenital Infections (UGI) are very prevalent during pregnancy and are admittedly one of the main causes of premature labor. Still, very little is known about the prevalence of UGI in the intrapartum period. Several variables can change the concentration of immunoglobulins in the colostrum. Prematurity and urogenital infections have been studied as some of these factors. Goal: Assessing the prevalence of urogenital infections in pregnant women during pre-term and fullterm labor; quantifying secretory IgA levels in the colostrum of pre-term and fullterm puerperal women with and without urogenital infection and correlate the levels of secretory IgA levels in the colostrum of pre-term and full-term mothers with urogenital infection. Methodology: 94 pregnant women in labor, who were admitted to Maternidade Escola Januário Cicco - Universidade Federal do Rio Grande do Norte, allocated in two groups, 49 in pre-term labor (PTL) and 45 in full-term labor (FTL), and were invited to participate in the study. For a better homogenization of results, only 72 mothers of PTL (34) and FTL (38) who manifested colostrum on the second day of puerperium had their levels of lgA quantified by immunoassay (ELISA). All these women signed a free and clarified consent term and underwent gynecological examination, when urine, vaginal and perianal samples were collected for microbiological study. Results: In 94 of the cases studied, the prevalence of general infections was 49.0% in the pregnant women in pre-term labor and 53.3% in the pregnant women in full-term labor (p=0.8300). Considering the cases of urogenital infections in both pre-term and full-term pregnant women, Urinary Tract Infection (UTI) was found in 36.7% and 22.2%, as well as Vaginal Candidiasis in 20.4% and 28.9%, Bacterial Vaginosis in 34.7% and 28.9% and Group B Streptococci in 6.1% and 15.6% respectively. Among the 72 PTN (34) and FTN (38) puerperal women studied, the prevalence of urogenital infections was 50.0% in PTN and 52.6% in FTN. Considering the cases of specific urogenital infections, in both PTN and FTN, Urinary Tract Infection (UTI) was found in 32.4% and 15.8%, and Vaginal Candidiasis in 17.6% and 26.3%, Bacterial Vaginosis in 38.2% and 31.6% and Group B Streptococci in in 5.9% and 15.8% respectively. The lgA concentrations were significantly higher in PTN puerperal women (1051.3 mg/dL) than in FTN puerperal women (396.3 mg/dL). Conclusions: The lgA levels in the colostrum of PTN mothers were significantly higher than that found in FTN mothers. However, in spite of the high prevalence of intrapartal genital infections, they did not have influence on the average levels of lgAs, suggesting this increase observed in the colostrum of PTN mothers might be related to adaptive factors of prematurity and not to the presence of infections / Doutorado / Fisiopatologia Ginecológica / Doutor em Ciências da Saúde

Orientador: Cleide Enoir Petean Trindade / Resumo: A incidência de displasia broncopulmonar (DBP) é alta em prematuros de muito baixo peso. Dentre os vários fatores implicados em sua patogênese tem-se destacado a deficiência de vitamina A como um importante fator contributivo. O presente estudo teve como objetivo determinar a condição de vitamina A em prematuros de muito baixo peso e avaliar a relação entre os níveis plasmáticos de retinol e a DBP. Após a obtenção do consentimento materno, foram coletadas amostras de sangue materno, do cordão umbilical e do recém-nascido com 3, 14 e 28 dias de vida, para as dosagens do retinol plasmático, que foram efetuadas por cromatografia líquida de alta resolução (HPLC). Foram estudados 34 recém-nascidos com peso de nascimento médio de 1156 g (± 248 g) e idade gestacional mediana de 30 semanas, os quais foram divididos em dois grupos: Sem DBP (n = 24) e Com DBP (n = 10). Nestes grupos analisou-se as características demográficas maternas e dos recém-nascidos, as condições de nascimento, a evolução clínica no período neonatal, os níveis plasmáticos de retinol e a oferta de vitamina A por via enteral e parenteral. Os resultados das variáveis clínicas foram analisados pelos testes t de Student e Mann-Whitney e comparados entre e dentro dos grupos pelo teste de associação de Goodman. Para a análise dos dados da vitamina A utilizou-se os testes de Wilcoxon (para 2 grupos e 2 momentos) e Freedman (para 2 grupos e 4 momentos). A correlação entre as variáveis foi feita pelo coeficiente de correlação de Pearson. O nível de significância foi de 5%. As características maternas e as condições... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The incidence of bronchopulmonary dysplasia (BPD) is high in preterm very low birthweight infants. Multiple factors have been implicated in its pathogenesis, and the deficiency of vitamin A has been described as an important contributing cause. Several studies have shown that premature infants have low vitamin A status at birth and this has been associated with increased risk of developing chronic lung disease, however many trails showed inconsistent effects of vitamin A supplementation on prevention of bronchopulmonary dysplasia. The purpose of this study was to determine vitamin A status in the very low birthweight infants and to evaluate the relationship between plasma retinol levels and BPD. After parental informed consent, the maternal and cord blood samples were obtained at delivery, and peripheral blood of the infants were drawn at day 3, 14 and 28 of life. Plasma retinol content was determined by high performance liquid chromatography. Thirty four infants (1156 g ± 248 mean birthweight and 30weeks median gestation age) were enrolled, and assigned to 2 groups as follows: BPD (n=10), No-BPD (n=24). The maternal and neonatal demographic data, birth condition... (Complete abstract, click electronic access below) / Doutor

A dor encontra-se inerente aos procedimentos de tratamento intensivo dos recém-nascidos pré-termo em Unidade de Terapia Intensiva Neonatal. As experiências precoces e repetidas de dor podem ter efeitos a longo prazo para os recém-nascidos vulneráveis. A Academia Americana de Pediatria e a Sociedade Pediátrica Canadense recomendam o uso da solução de sacarose como rotina para alívio da dor em Unidade de Terapia Intensiva Neonatal, durante os procedimentos invasivos e dolorosos. O presente estudo teve por objetivo avaliar as reações de dor de neonatos pré-termo durante procedimento de coleta de sangue, analisando o momento da punção, assim como os efeitos do manuseio dos neonatos para a anti-sepsia e o curativo e avaliar a eficácia da intervenção com solução de sacarose a 25% no alívio da dor administrando-a em dose única de 0,5ml/Kg. Trinta e três neonatos foram distribuídos randomicamente em dois grupos: Grupo Sacarose (n=17) e Grupo Água (n=16). Os neonatos foram avaliados durante dois dias consecutivos. Na primeira avaliação, os neonatos de ambos os grupos não receberam nenhuma substância antes do procedimento doloroso. Na segunda avaliação, o Grupo Sacarose recebeu sacarose oral e o Grupo Água recebeu água estéril, dois minutos antes do procedimento invasivo e doloroso de punção para coleta de sangue. Cada avaliação foi dividida em cinco fases: Linha de Base, Preparação para Punção (anti-sepsia), Punção, Recuperação com Manuseio (curativo) e Recuperação sem Manuseio. O indicador de dor foi avaliado pela atividade facial, que foi mensurada pelo Neonatal Facial Coding System. O nível de ativação dos neonatos foi medido pelo estado de vigília e sono e pela freqüência cardíaca. A análise entre grupos e intra-grupo dos dados revelou que no primeiro dia de avaliação os neonatos anteciparam a reação ao estímulo doloroso de punção, apresentando elevação significativa dos indicadores atividade facial, estado de vigília e sono e freqüência cardíaca avaliados na Preparação para Punção. Ambos os grupos mostraram alta reatividade comportamental e fisiológica na fase de Punção, em comparação à Linha de Base. Durante a recuperação, o indicador fisiológico de freqüência cardíaca continuou elevado. No segundo dia de avaliação os neonatos que receberam 0,5ml/Kg de solução de sacarose a 25% apresentaram menores escores de atividade facial, indicativo de menos dor, em comparação aos neonatos que receberam água estéril, antes, durante e após o procedimento de punção para coleta de sangue. Entretanto, o indicador fisiológico de freqüência cardíaca não apresentou diferença significativa entre os grupos. Conclui-se que a dose de 0,5ml/Kg de solução de sacarose a 25%, recomendada para a administração da substância em doses repetidas, foi eficaz no alívio de dor, avaliada por meio da redução de indicadores comportamentais. Entretanto, o indicador fisiológico continuou elevado, sugerindo a necessidade de outras medidas de conforto associadas à sacarose, com a finalidade de atenuação do estado de ativação e irritabilidade do sistema nervoso central. / Pain is inherent to the intensive treatment procedures offered to preterm neonates in Neonatal Intensive Care Units. The early and repeated experiences of pain may have a long-term effects for the vulnerable neonates. The American Academy of Pediatrics and the Canadian Pediatric Society recommend using a sucrose solution for pain relief in NICU during invasive and painful procedures. The present study had the purpose to assess the pain reactions of preterm neonates during a procedure for blood collection, evaluating the moment of puncture as well as the effects of handling the neonates for antisepsis and for bandages, and evaluating the efficacy of the intervention with the sucrose solution at 25% for pain relief by administering a single dose of 0.5 ml/Kg. Thirty-three neonates were randomly assigned to two groups: Sucrose Group (n=17) and Water Group (n=16). The neonates were evaluated during two consecutive days. In the first assessment, the neonates from both groups did not receive the solution before the painful procedure. In the second assessment, the Sucrose Group received oral sucrose and the Water Group received sterile water, two minutes before the invasive painful procedure of puncture for blood collection. Each evaluation was divided into five phases: Baseline, Preparation for Puncture (antisepsis), Puncture, Recovery with Handling (bandage), and Recovery without Handling. The indicators of pain were evaluated by the facial activity, measured by the Neonatal Facial Coding System. The level of activation of the neonates was measured by their sleep-awake state and heart rate. The between and within-group data analysis revealed that, on the first day of evaluation, the neonates anticipated their reaction to the painful puncture stimulus, and showed a significant increase in the behavioral indicators of facial activity, sleep-awake state, and heart rate evaluated at the Preparation for Puncture. Both groups showed a high behavioral and physiological reactivity in the Puncture phase, in comparison to the Baseline. During recovery, the physiological indicator of heart rate continued high. In the second day of evaluation, the neonates who received 0.5 ml/Kg of the sucrose solution at 25% showed lower scores of facial activity, which indicates they experienced less pain in comparison to the neonates who received sterile water before, during, and after the procedure of puncture for blood collection. However, there were no significant differences in terms of the physiological indicator of heart rate. It is concluded that the dose of 0.5 ml/kg of sucrose solution at 25%, recommended for the administration in repeated doses, was efficient for pain relief, evaluated by means of the reduction of behavioral indicators. However, the physiological indicator remained high, which suggests there is a need for other comfort manegement associated to sucrose, with the aim to diminish the state of activation and irritability of the central nervous system.

abstract: Late preterm infants (LPIs), born between 34 and 37 weeks gestation, are at risk for a myriad of health conditions related to neuro-muscular and physiologic immaturity. However, relative stability allow many of these infants to avoid care in specialty nurseries and discharge home with their mothers after birth. Due to underlying immaturity, feeding difficulty is the most common issue LPIs experience, resulting in early breastfeeding cessation, increased risk for secondary diagnoses, and hospital readmission. The purpose of this study was to assess early breastfeeding behavior of LPIs, including testing inter-rater reliability of an assessment tool and the feeding patterns of infants over time. An extensive review of breastfeeding assessment tools resulted in the selection of the Premature Infant Breastfeeding Behavior Scale (PIBBS) based on its reliability and validity in the preterm infant population. A convenience sample of LPI dyads was recruited and used to conduct inter-rater reliability testing of PIBBS. A longitudinal one-group non-experimental study was used for observational follow-up. A strong statistical agreement of PIBBS scores occurred between mothers and a healthcare professional (Cohen’s kappa values of items ranged from .776 to 1.000, p = <.001). Participants continued using the PIBBS tool after hospital discharge until their infants expected due dates (40 weeks adjusted age). T-test analyses were conducted to examine changes in scores over time indicating increase in item scores (p = .003 - .193). PIBBS appears to be a valid and reliable tool to assess breastfeeding among LPI dyads. Incorporation of PIBBS into a comprehensive plan of care could better support and protect breastfeeding among the LPI population. / Dissertation/Thesis / Doctoral Dissertation Nursing and Healthcare Innovation 2018

Preterm birth is defined as delivery prior to 37 weeks’ completed gestation. It affects an average of 11% of pregnancies worldwide and is the leading cause of death in children under age 5. Many studies have identified associations between pregnancy lipid levels and increased risk for preterm birth. This thesis investigates the role of genetic variability associated with lipids and its relationship with preterm birth, and the relationship between pre-pregnancy dyslipidemia and risk for preterm birth. Genetic variability in the form of single-nucleotide polymorphisms, previously identified by genome-wide association studies for association with lipid levels, was analyzed for association with risk for preterm birth. The study population included 992 women in California with banked 2nd trimester serum samples. Serum lipid levels and DNA were used. Genetic risk scores were constructed for each subject using published SNPs associated with lipid levels as an indicator of genetic burden. These genetic risk scores were then analyzed for association with risk for preterm birth. The GRS were not associated with the overall risk for preterm birth. However, a higher HDL-C GRS was associated with increased risk for spontaneous preterm birth. Higher triglyceride and total cholesterol GRS were associated with decreased risk for spontaneous preterm birth. The relationship between pre-pregnancy dyslipidemia and risk for preterm birth was assessed in a cohort of 2,962,434 women giving birth in the state of California from 2007-2012. Dyslipidemia, as defined by medical diagnostic codes, was associated with a 1.5-fold increase in risk for preterm birth. This association was consistent across race/ethnicity, body mass index, type of dyslipidemia, and type of preterm birth. This thesis identified counter-intuitive associations between lipid GRS and spontaneous preterm birth, while also identifying a strong relationship between pre-pregnancy dyslipidemia and all types of preterm birth including spontaneous. Together, these findings suggest that the previously reported associations between lipids and preterm birth may be reflecting unidentified dyslipidemias. One possible interpretation of the counter-intuitive genetic findings is that while extreme dyslipidemia predisposes to preterm birth a genetic predisposition to low total cholesterol also confers increased risk for spontaneous preterm birth. An alternative explanation is that these results are simply an artefact of the data and additional genetic loci and lifestyle factors confer stronger effects on risk for spontaneous PTB than the effects of the genetic loci included in this thesis.