Caffeine is used for the treatment of apnea of prematurity. The objective of this study was to determine the long term neuropathological and neurobehavioral effects of caffeine on the immature rat brain. Newborn rats were injected with either caffeine, or normal saline from postnatal days 3 to 7, equivalent to the human premature infant of 28-36 weeks. Behavioral tests revealed no abnormality in caffeine treated animals compared to controls. Fluro-Jade B stain of P4 rat brains showed that caffeine caused significant neuronal cell death in some areas of the brain, compared to controls, but this alteration was transient and not present at P8. Anti-NeuN stain at P21 showed significant neuronal cell loss in CA1 and hypothalamus regions in the caffeine group, but not at P160. Anti-Neurofilament M stain at P8, P21 and P160 showed no differences between the control and caffeine groups. We conclude that use of caffeine has no significant effect on the behavioral tests measured in our newborn rat pups. While caffeine caused neuronal cell death at P4, and neuronal cell loss in CA1 and hypothalamus regions at P21, there was no long-lasting effect on neuropathological outcome. However, given these latter findings, the use of caffeine in the premature infant must still be done with caution. / Medical Sciences

Very preterm birth is an important developmental and public health concern, with clear evidence to suggest that very preterm children may be at long term risk of neurodevelopmental impairment and educational difficulties. Although a great deal is known about the neurodevelopmental outcomes associated with very preterm birth,comparatively little is known about the social competence of children born very preterm during the important early childhood period. Therefore, as part of a prospective, longitudinal study, this research examined the social competence of 105 children born very preterm (birth weight <1,500 g and/or gestational age ≤33 weeks) and 108 full term comparison children (gestational age 37-40 weeks) at age 4 years (corrected for extent of prematurity at birth). The aims of this study were 1) to examine the social competence of a regional cohort of children born very preterm and full term comparison children at age four years, 2) to identify infant clinical factors and socio-familial characteristics associated with poor social competence amongst children born very preterm, and 3) to examine the predictive validity of social competence problems amongst both very preterm and full term preschoolers in relation to school academic functioning and behavioural adjustment at age 6 years. At age 4, children were assessed using a range of parent and/or teacher completed questionnaires, spanning emotional regulation, behavioural adjustment and interpersonal social behaviour. Measures included the Emotion Regulation Checklist, the Infant-Toddler Symptoms Checklist, the Strengths and Difficulties Questionnaire, the Behaviour Rating Inventory of Executive Functioning “ Preschool version and the Penn Interactive Peer Play Scale. In addition, as part of a structured research assessment, children completed a battery of false belief tasks and a short form version of the Weschler Preschool and Primary Scales of Intelligence. Two years later at age 6, school teachers qualitatively rated children's behavioural adjustment and academic achievement in math, reading, spelling and language comprehension compared to their classroom peers. Results showed that relative to their full term peers, some children born very preterm tended to score less well across several areas of social competence. Specifically, parent report showed that children born very preterm were more likely to be characterised by higher levels of emotional dysregulation (p=.002) as well as a range of behavioural adjustment problems, spanning inhibitory control problems (p=.03), hyperactivity/inattention (p=.01), conduct problems (p=.01) and emotional symptoms (p=.008). While elevated rates of behavioural adjustment difficulties were also evident amongst very preterm children within the preschool environment, group differences were not statistically significant. However, a statistical trend towards elevated risk of inhibitory control problems amongst very preterm children in the preschool environment was noted (p=.09). Further, children born very preterm were at around a four-fold risk of emotional regulation difficulties of clinical significance,as well as being around 1.5 times more likely to exhibit clinically significant externalising and internalising behavioural difficulties and interpersonal social problems at age 4 years. In contrast, the interpersonal social behaviours and the extent of social cognitive understanding were largely similar across both groups. This pattern of findings remained largely unchanged following statistical control for the selection effects of family socio-economic status. Amongst children born very preterm, significant infant clinical and sociofamilial predictors of both emotional dysregulation and externalizing behaviour were male gender (p=.008/p=.006), neonatal indomethacin (p=.002/p=.005) and elevated maternal anxiety (p=.009/p=.002). Emotional dysregulation was also predicted by low socio-economic status (p=.002). In contrast, internalising behaviour was predicted only by low birth weight (p=.03). Finally, across both groups significant associations were found between overall social competence problems at age 4 years and later school adjustment with those very preterm and full term preschoolers characterised by poor social competence being at elevated risk of a range of behavioural adjustment difficulties and poor academic functioning in reading, spelling and math at age 6 years (corrected). Links between poor social competence and later behavioural adjustment remained across both groups following statistical control for child IQ, while associations with academic functioning were largely attenuated. By age 4 years a number of very preterm children are beginning to display elevated levels of emotional dysregulation, hyperactivity/inattention, conduct problems and emotional symptoms. Further, a substantial proportion of very preterm children may be at risk of developing clinically significant difficulties with these most pronounced in terms of emotional regulation abilities. Children's abilities to regulate their emotions and behaviour represent important building blocks for their later social and emotional functioning. Further, these abilities will likely influence the extent to which children are able to successfully transition to school. Therefore,alongside other important aspects of development, these findings highlight the importance of monitoring the social abilities of preschoolers who were born very preterm across a range of developmental domains and contexts. Preschoolers characterised by emotional, behavioural and/or interpersonal difficulties could then receive targeted intervention aimed at facilitating their social competence prior to school entry.

BACKGROUND: Despite decades of research aimed at prevention, preterm birth remains an enormous leading cause of infant mortality in the United States and worldwide. Of concern, racial disparities in preterm birth remain an intractable public health issue. In an effort to reduce preterm birth, organizations such as the American Congress of Obstetricians and Gynecologists (ACOG) released policy statements in 2009 aimed at reducing early elective deliveries. Subsequently, the incidence of preterm birth in the United States has decreased, but whether this decrease is due to a reduction in iatrogenic or "medically-indicated" preterm birth is unknown. Further, the effect of the reduction in early elective deliveries on racial disparities is unknown. Our hypotheses were that 1) after 2009, preterm births would be less likely to be medically-indicated than due to spontaneous causes and 2) black-white differences in preterm births would be unchanged. OBJECTIVES: 1) Determine the proportion of preterm deliveries at Beth Israel Deaconess Medical Center (BIDMC) from 2004-2013 that were medically-indicated versus spontaneous. 2) Due to persistent disparities, determine if shifts in type of preterm delivery varied by race/ethnicity. METHODS: We reviewed the first 87 deliveries in 2013 and randomly selected 15% of the records for each year from 2004-2013. Additionally, we reviewed 69 charts to oversample black women's deliveries. We manually abstracted data from BIDMC's online medical record and designated each delivery as either medically-indicated (preeclampsia, poor fetal growth, hypertension, or other fetal/maternal condition) or spontaneous (preterm labor, preterm premature rupture of membranes or cervical incompetence). Two reviewers independently reviewed 18 records for concordance of medically-indicated versus spontaneous preterm birth typing. If the first reviewer could not phenotype the delivery, then a neonatologist and obstetrician were consulted. We reviewed 971 out of the 5,566 preterm deliveries and included 930 that were confirmed preterm and had a clear medically-indicated or spontaneous phenotype. We dichotomized the time period into early (2004-2009) and late (2010-2013). Statistical methods included comparisons of early versus late using Chi-Square tests, logistic regression models to adjust for potential confounding variables, and stratified analyses (singletons and black versus white). RESULTS: There were 46,981 deliveries at our institution during the study period, 5,566 of which were preterm. Among the 930 preterm deliveries sampled from the 10-year period, 45.6% were medically-indicated with a non-significant, subtle difference between the early (48.3%) and late (41.9%) (P=0.05) time periods. The odds ratios of medically-indicated versus spontaneous preterm birth in late versus early were 0.77 (P=0.05) and 0.73 (P=0.03) for all participants, unadjusted and adjusted, respectively. While not statistically significant, a higher proportion of preterm deliveries among black women were medically-indicated in the early (50.4%) versus late (40.6%) periods (P=0.19). There was a similar trend among white women between the early (50.0%) and late (46.9%) periods (P=0.48). The odds ratios of medically-indicated versus spontaneous preterm birth from late versus early were 0.67 (P=0.19) and 0.63 (P=0.14) for black participants, unadjusted and adjusted, respectively. For white participants, the odds ratios were 0.88 (P=0.48) for unadjusted and 0.80 for adjusted (P=0.20). Overall at BIDMC, the preterm delivery rate was significantly higher in the early period (12.3%) compared to the later period (11.2%) (P=0.0003). While we observed a reduction of preterm birth among all women, black women experienced a 20.8% decrease (from 16.2% in the early period to 12.8% in the late) in preterm birth, while white women experienced just a 4.9% decrease (from 12.4% to 11.7%), resulting in a narrowing of the racial disparity of preterm birth in our institution. CONCLUSION: At a Massachusetts birth hospital we found a reduction in the incidence of preterm deliveries over a 10-year period that coincided with policy efforts to reduce early elective deliveries. There was a reduction in the proportion of preterm births that were medically-indicated from 48.3% to 41.9%. The reduction in medically-indicated preterm birth was most evident among black women at BIDMC with concurrent decrease in the overall preterm birth rate among black women resulting in a near elimination of the racial disparity in preterm birth at BIDMC. Future work includes statistical analysis to account for the oversampling of deliveries in 2013 as well as oversampling of black women's deliveries using inverse probability weighting. We also plan to analyze which underlying conditions (preeclampsia, intrauterine growth restriction, fetal distress, etc.) were responsible for the reduction of the medically-indicated deliveries.

Philosophiae Doctor - PhD / The aim of the study was to detect the prevalence of AV and its associated bacteria with preterm delivery in the Western Cape, South Africa. Furthermore, it sought particularly to examine and investigate the predictive value of GBS and E. faecalis for preterm delivery (PTD). It also aimed to establish other factors which may predict adverse pregnancy outcomes. Three hundred and one pregnant women were recruited from four different antenatal in the Western Cape, South Africa. The study conformed with the Declaration of Helsinki (2013). Maternal data was collected from a questionnaire and maternal medical records. Vaginal and rectal swabs were collected and microscopically examined for AV, followed by culture characterization of GBS and E. faecalis. Antimicrobial susceptibility testing was also performed. In this study, AV was detected in 79 (26.2%) of the 301 pregnant women, and GBS and E. faecalis isolated from 50 (16.6%) and 21 (7.0%) respectively. GBS serotype V was the predominant serotype, followed by serotype III. Pulse field gel electrophoresis (PFGE) profile analysis for both GBS and E. faecalis yielded a total of 24 restrictions profiles for GBS and 16 for E. faecalis. Multivariable analysis revealed that parity, gravidity, vaginal discharge, urinary tract infection, and smoking were significantly associated with PTD. The results from the study provides improved guidelines maternal screening of pregnant women. The early detection of AV-related bacteria may significantly reduce maternal and neonatal morbidity.

Preterm infants are at increased risk of cardiometabolic and neurodevelopmental disorders in later life. The typical postnatal growth pattern of failure to achieve the equivalent of a normal fetal growth rate, followed up by catch-up growth, altered adiposity and altered hypothalamic-pituitary-adrenal axis (HPA) activity may be predisposing factors. Potential mechanisms that may mediate such programmed effects include altered DNA methylation and faster telomere attrition. A prospective cohort of 46 very preterm (25+2 to 31+5 weeks’ gestation, mean 28.6) and 40 full term (38+3 to 42+2 weeks’ gestation, mean 40.2) infants was established to investigate potential mechanisms. Infants were studied at birth, term equivalent age, 3 months and 1 year corrected for prematurity. At all time points, linear growth and body composition (by densitometry) were measured and buccal (epithelial) cells was collected for measurement of DNA methylation (5mC) and relative telomere length. Compared with full term infants, preterm infants were lighter (p < 0.001) and had a smaller head circumference (p < 0.05) at all time-points and were shorter at term equivalent (p < 0.001) and 3 months corrected age (p = 0.002). Preterm infants also had greater percentage body fat at term equivalent age (mean difference = 5.5%, p < 0.001), which normalised by 3 months corrected (mean difference = 0.9%, p = 0.4). Preterm infants had a blunted salivary cortisol response (mean difference 0.4 μg/dL, p = 0.02) to a stressor (physical examination) at 3 months compared to term infants at this age, suggesting altered activity of the HPA axis. 5mC is fundamental in the control of expression of imprinted genes involved in fetal growth. Notably, a number of studies in humans exposed to an adverse environment in early life have demonstrated altered 5mC at the differentially methylated regions (DMRs) controlling the expression of the key fetal growth factor insulin like growth factor 2 (IGF2) and at the linked H19 imprinting control region (H19 ICR). At birth, preterm infants had a significant decrease in 5mC at DMR2 compared with term infants at birth (β = –11.5, p < 0.001) and compared with preterm infants at term equivalent age (mean difference = -7.4, p = 0.01). By term equivalent age, preterm infants had decreased 5mC at both DMR2 (β = –2.8, p = 0.01) and the H19 ICR (β = –2.3, p = 0.048) compared with term infants at birth, although this difference disappeared at 1 year corrected. Although research has suggested that catch up growth may confer an unfavourable metabolic phenotype, poor initial weight gain can associate with worse cognitive outcome. A pathway was established for obtaining advanced magnetic resonance images of the preterm brain. 5mC at H19 ICR and DMR2 in buccal DNA showed no association with measures of white matter microstructure or whole brain volumes. Term infants demonstrated telomere lengthening over the first year of life (mean difference = -0.3, p = 0.02). There was no significant change in telomere length over the first year of life in preterm infants (mean difference = 0.2, p = 0.34). However, as preterm infants at term equivalent age had longer telomeres compared to term infants at birth (β = 0.6, p < 0.001), ultimately there were no differences between the term and the preterm groups at 1 year corrected age (β = 0.3, p = 0.07). The DNA modification 5-hydroxymethylcytosine (5hmC) is a stable modification in its own right and is also thought to be an intermediate step in DNA demethylation. 5hmC is abundant in the placenta but has not been studied in the context of fetal programming. Additionally, previous research using methods such as bisulphite conversion would not have discriminated between 5mC and 5hmC and therefore the role of 5mC may not have been accurately measured. To study the relationship between 5mC, 5hmC and fetal growth, gene expression of candidate imprinted and non-imprinted genes in full term placental samples from the Edinburgh Reproductive Tissue BioBank was analysed. 5mC and 5hmC within the IGF2/H19 and KvDMR (controlling CDKN1C) loci was estimated using chemical capture and immunoprecipitation techniques that discriminate between modifications. Relationships between the expression of IGF2 (r = 0.3, p = 0.02) and CDKN1C (r = -0.3, p = 0.01) and birth weight across the normal range were found and in keeping with the known action of these genes. 5mC at IGF2 DMR0 (β = 0.3, p = 0.02) and KvDMR (β = 0.3, p = 0.02) and 5hmC at H19 gene body (β = 0.2, p = 0.04) associated with birth weight. Thus, DNA modifications at imprinted DMRs may modulate environmental influences on fetal growth across the normal range. DNA methylation at IGF2/H19 can be influenced by early life events. It remains to be seen whether any changes are present later in childhood and whether they associate with risk factors for the metabolic syndrome.

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Ansai Pereira de Castro - 12-04.pdf: 1164263 bytes, checksum: b49eb19a6a2a971e2f6eb0a32c2114a9 (MD5) / Approved for entry into archive by LUIZA DE MENEZES ROMANETTO (luizamenezes@reitoria.unesp.br) on 2017-04-13T13:15:43Z (GMT) No. of bitstreams: 1 castro_rsap_me_bot.pdf: 1164263 bytes, checksum: b49eb19a6a2a971e2f6eb0a32c2114a9 (MD5) / Made available in DSpace on 2017-04-13T13:15:43Z (GMT). No. of bitstreams: 1 castro_rsap_me_bot.pdf: 1164263 bytes, checksum: b49eb19a6a2a971e2f6eb0a32c2114a9 (MD5) Previous issue date: 2017-04-12 / Introdução: A sepse e choque séptico são importantes causas de morbimortalidade no período neonatal. A implantação de protocolos permite uma condução sequencial e rápida na sepse/ choque, o que pode melhorar o prognóstico desses pacientes. Objetivo: Investigar nos prematuros de muito baixo peso (PT-MBP) se o quadro séptico está sendo conduzido de forma sistematizada de acordo com o protocolo e se essa sistematização melhorou o prognóstico em curto prazo. Métodos: Estudo retrospectivo, do tipo coorte realizado na UTI Neonatal do Hospital das Clinicas da Faculdade de Medicina de Botucatu no período de janeiro de 2013 a dezembro de 2015, após aprovação do CEP. Foram selecionados todos os recém-nascidos (RN) prematuros com peso ao nascer inferior a 1500g (muito baixo peso), internados na UTI, nascidos ou não no Serviço, que sobreviveram por mais de 72 horas de vida. Foram incluídos todos os prematuros menores de 34 semanas e que apresentaram diagnóstico de sepse / choque séptico na Unidade. Não foram incluídos aqueles com malformações múltiplas e infecções congênitas. Variáveis estudadas: maternas, gestacionais, neonatais e variáveis do protocolo de choque da Unidade. Os recém-nascidos (RN) foram comparados inicialmente em dois grupos: sepse e choque séptico; para a avaliação do protocolo foram estudados apenas os que evoluíram para choque: com protocolo VS sem protocolo. Desfechos: displasia broncopulmonar (DBP), hemorragia periintraventricular (HPIV) grave, retinopatia da prematuridade (ROP) ≥ estágio 2 e óbito. Estatística: testes paramétricos e não paramétricos, com significância se p<0,05. Resultados: Dentre os 271 PT-MBP admitidos, a incidência de sepse tardia foi de 34%, e do choque séptico foi de 14%. A mortalidade entre os pacientes sépticos foi de 27,5%, e no choque foi de 61%. Abordagem sistematizada do choque de acordo com o protocolo ocorreu em 61% dos casos e os prematuros que não seguiram protocolo apresentaram maior mortalidade (80% x 48%; p=0,047). Não houve diferença significativa em relação às demais comorbidades, porém elas foram mais frequentes no grupo não seguiu o protocolo: DBP (75% vs 33%; p=0,262), HPIV grave (40% vs 22%; p=0,225), ROP ≥ 2 (50% vs 29%; p=1,000). Conclusão: Prematuros com choque séptico apresentaram alta mortalidade e pior prognóstico. Não seguir protocolo aumentou o percentual de morte. Prematuros com choque séptico sem abordagem sistematizada apresentaram pior prognóstico em curto prazo, embora sem diferença significativa, porém com alta relevância clínica. Assim, a abordagem sistematizada do choque pode melhorar o prognóstico desses RN. / Introduction: Sepsis and septic shock are important causes of morbidity and mortality in the neonatal period. Protocol implantation allows sequential and rapid conduction of sepsis / shock, which may improve patient prognosis. Objective: To investigate in the very low birth weight preterm infants if septic disease is being conducted in a systematized manner according to the protocol and if this systematization has improved the prognosis in the short term. Methods: Retrospective cohort study performed at the neonatal intensive care unit (NICU) of the Clinic Hospital Botucatu Medical School from January 2013 to December 2015. All preterm infants with birth weight less than 1500g, admitted in the NICU with more than 72 hours of life were selected and included whose with diagnosis of sepsis / septic shock. Those with multiple malformations and congenital infections were excluded. Variables studied: maternal, gestational, neonatal and variables of the shock protocol. The neonates were initially compared in two groups: sepsis and septic shock; for an evaluation of the protocol it was studied only those who evolved to shock: protocol VS non-protocol. Outcomes: Bronchopulmonary dysplasia (BPD), Grade III or IV intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP) ≥ stage 2 and death. Statistical: parametric and non-parametric tests, with significance if p <0.05. Results: Among the 271 very low birth weight preterm admitted, the incidence of late onset neonatal sepsis and septic shock was 34% and 14%, respectively. Mortality among sepsis neonates was 27.5%, while in the shock group was 61%. Systematic approach according to the protocol occurred in 61% of the cases and the preterm infants who did not follow the protocol presented higher mortality (80% x 48%, p = 0.047). There were no statistically difference in the others comorbidities, but they were more frequent in the non-protocol group: BPD (75% vs 33%; p=0,262), Grade III or IV IVH (40% vs 22%, p = 0.225), ROP ≥ 2 (50% vs 29%, p = 1,000). Conclusion: Preterm infants with septic shock had high mortality and worse prognosis. Not following the protocol increased the percentage of death. Preterm infants with septic shock without systematic approach had worse prognosis in the short term, although without significant difference. Therefore, sequential conduction may be useful to improve prognosis in neonates.

Orientador: Lígia Maria S. S. Rugolo / Banca: Cleide Enoir Petean Trindade / Banca: José Carlos Peraçoli / Banca: Maria Fernanda Branco de Almeida / Banca: Lilian dos Santos Rodrigues Sadeck / Resumo: A rotura prematura de membranas pré-termo (RPM-PT) é uma das principais causas de morbimortalidade perinatal e fator de risco para infecção neonatal precoce. As citocinas pró-inflamatórias TNF-α, IL-8 e a antiiflamatória IL-10 são importantes mediadores da resposta imune, e na situação de risco infeccioso podem ser adjuvantes úteis no diagnóstico de infecção neonatal. Investigar se os níveis de TNF-α, IL-8 e IL-10 em sangue de cordão umbilical são marcadores de infecção precoce em prematuros advindos de gestações com RPM-PT. Estudo clínico, prospectivo e do tipo teste diagnóstico, realizado no Serviço de Obstetrícia e Neonatologia da Faculdade de Medicina de Botucatu, envolvendo prematuros de gestantes com rotura de membranas ≥ 12 horas. As citocinas TNF-α, IL-8 e IL-10 foram dosadas em sangue de cordão umbilical pelo método ELISA. Conforme a evolução clínica e laboratorial dos recém-nascidos foram constituídos dois grupos: Infectado e Não infectado, os quais foram comparados quanto às variáveis perinatais e neonatais por análise estatística univariada; com significância em 5%. A acurácia do teste diagnóstico foi obtida pela curva ROC, sendo calculados: sensibilidade, especificidade, valor preditivo positivo (VPP) e negativo (VPN). Foram estudados 55 prematuros: 27 infectados e 28 não infectados. O tempo de rotura não diferiu entre os grupos (54 x 29 hs; p=0,102) mas, no grupo infectado corioamnionite clínica e histológica foi mais frequente; a idade gestacional (31 x 33 semanas; p<0,001) e o peso de nascimento (1707 x 2109g; p=0,003) foram menores; a morbidade foi maior desde o nascimento com necessidade de assistência mais intensiva e o óbito ocorreu somente nesse grupo. As medianas de TNF-α (3.67 vs 1.76 pg/ml; p =0.084) e IL-10 (0 vs 4.10 pg/ml; p=0.291)... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Preterm premature rupture of membranes (PPROM) is one of the major causes of perinatal morbidity and mortality, and an important risk factor for early-onset neonatal infection. The pro-inflammatory cytokines TNF-α, IL-8 and anti-inflammatory cytokine IL-10 are mediators of immune response and may be helpful as early indicator of neonatal infection in the presence of perinatal risk factor. To evaluate umbilical cord blood levels of TNF-α, IL-8 and IL-10 as markers for early-onset infections in premature infants from pregnancies complicated by PPROM. Clinical, prospective and diagnostic test study performed at Obstetrician and Neonatal Unit of Botucatu School of Medicine, enrolling premature infants from pregnant women with ≥ 12 hours of premature rupture of membranes. TNF-α, IL-8 and IL-10 cytokines were measured in umbilical cord blood by ELISA. According to clinical and laboratorial evaluation patients were classified into two groups: infected and noninfected. Perinatal and neonatal variables were studied. Comparisons between groups were performed by univariate statistical analysis; significance at p <0.05. The diagnostic test accuracy was obtained by ROC curve. Sensibility, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated by comparing infected with noninfected group. 55 premature infants were studied: 27 infected and 28 noninfected. There was no difference between the groups in the latency period (54 x 29 hours; p=0,102). In the infected group, clinical and histological chorioamnionitis were more frequent, gestational age (31 x 33 weeks; p<0,001) and birth weight(1707 x 2109g; p=0,003) were lower. Morbidity, mortality and resource use were higher among infected premature infants. The median levels of TNF-α (3.67 vs 1.76 pg/ml; p=0.084)... (Complete abstract click electronic access below) / Doutor

nÃo hà / Os riscos podem ser conceituados como os problemas ocorridos na gestaÃÃo e parto, quanto pelas patologias desenvolvidas durante o perÃodo de hospitalizaÃÃo. Atualmente os cuidados a esses recÃm-nascidos de risco sÃo realizados por uma equipe composta de vÃrios profissionais, entres eles, o fonoaudiÃlogo, tendo por objetivo melhorar as condiÃÃes de saÃde desses recÃm-nascidos, procurando a diminuiÃÃo da mortalidade e morbidade tardia (MODES; ALMEIDA, 2005). Desta Forma, esta pesquisa teve como objetivo avaliar os fatores associados à perda auditiva em recÃm-nascidos prÃ-termos submetidos à amicacina atravÃs de respostas obtidas por meio de exames eletrofisiolÃgicos. A pesquisa tratou-se de um estudo de coorte, quantitativo, descritivo de seguimento prospectivo e longitudinal realizado com 299 RN prÃ-termos, dos quais 254 recÃm-nascidos fizeram uso de amicacina e 45 recÃm-nascidos nÃo fizeram uso de amicacina. A associaÃÃo entre cada fator de risco e a ocorrÃncia de alteraÃÃo auditiva na avaliaÃÃo com EOAT foi significativa para UTI, Incubadora, Peso, PIG, AnÃxia, Hiperbilirrubinemia e VentilaÃÃo MecÃnica, e ainda para MÃ-formaÃÃo e HistÃrico Familiar. A associaÃÃo entre cada fator de risco e a ocorrÃncia de alteraÃÃo auditiva pela avaliaÃÃo do PEATE-A foi significativa para UTI, Incubadora, Peso, PIG, AnÃxia, Hiperbilirrubinemia e VentilaÃÃo MecÃnica. Em relaÃÃo Ãs alteraÃÃes avaliadas pelo PEATE-A em conjunto, a AnÃxia foi significativamente associada, indicando que a existÃncia da AnÃxia aumenta a chance de alteraÃÃo auditiva em aproximadamente 10 vezes. A variÃvel ototÃxico nÃo foi associada significativamente à ocorrÃncia de alteraÃÃo auditiva, nem individualmente, nem em conjunto, demonstrando que nÃo se pode afirmar que o ototÃxico tem efeito na alteraÃÃo auditiva quando avaliada pela tÃcnica do PEATE-A. A partir dos dados obtidos podemos concluir que a AnÃxia foi o Ãnico fator de risco estatisticamente significante nos recÃm-nascidos prÃ-termos, quando avaliado pelas EmissÃes OtoacÃsticas Transientes (EOAT) e pelo Potencial Evocado Auditivo de Tronco EncefÃlico AutomÃtico (PEATE-A). / The risks can be described as problems during pregnancy and labor, and by the pathologies during hospital time. Nowadays a team of several professionals, among them, the fonoaudiologist, take care of these newborn babies, having as an objective improve the health conditions of these babies, trying to low mortality rates and late morbidity.(MODES;ALMEIDA, 2005). This way, this research had as an objective to evaluate the factors associated to hearing loss in premature babies treated with amikacin using results obtained through electrophysiological examination. The research was a quantitative , descriptive, prospective and longitudinal cohort study that was performed with 299 premature newborn babies. In the study, 254 babies were treated with ototoxic and 45 were not. The risk factors found in the newborn babies were: Ototoxic, Mechanical Ventilation, Hyperbilirubinaemia, PIG, PN<1500g , Family history for hearing disturb, ICU, Incubator time, Anoxia and Malformation. The detection of hearing disturb in the techniques used, shows that the PEATE-A is more specific to detect hearing disturb than EOAT. The association among each risk factor and the ocurrence of hearing disturb when EOAT was used was significant for IUC, Incubator, Weight, PIG, Anoxia, Hyperbilirubinaemia and Mechanical Ventilation. Regarding the disturbs analyzed by PEATE-A, Anoxia was significantly associated , showing that the presence of anoxia increases the chance of hearing disturb in about 10 times. The variable Ototoxic was not significantly associated to hearing alteration, neither individually or in group, showing that it is not possible to affirm that ototoxic has effect in hearing alteration when evaluated by PEATE-A. Analyzing the data obtained we can conclude that anoxia was the single significantly risk factor to the newborn premature babies when evaluated by Transient Otoacoustic Emissions (TOAE) and Brainstem Auditory Evoked Potential (BAEP).

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).

Abstract The aim of this study was to examine the effect of preterm birth on the development of the dentition. The spesific aims were to examine the effect on deciduous and permanent tooth crown dimensions, the eruption of permanent teeth and the sagittal occlusal relationships within the dentition. The subjects consisted of 328 prematurely born (&lt; 37 gestational weeks ) white and black children and 1804 control children, who participated in the cross-sectional study of the Collaborative Perinatal Project (USA) in the 1960's and 1970's. Dental examinations, including dental casts were performed at the age of 6–12 years. Tooth crown size measurements, recording of the sagittal occlusal relationships and tooth eruption stages were performed by examining the dental casts. In general larger permanent tooth crown dimensions were found in preterm white boys and black girls and smaller permanent tooth crown dimensions in preterm white girls and black boys. There were both increased and decreased deciduous tooth crown dimensions in preterm children compared to controls, but no significant differences were found. Boys had larger tooth crown sizes than girls within all preterm and control groups showing sexual dimorphism. The results showed earlier eruption of permanent incisors and first molars in all preterm children compared to controls and also according to sex and race. Concerning the sagittal occlusal relationships, the results showed greater prevalence of prenormal canine relationships in preterm group than in the controls. When the molar relationships were concerned, the prevalence of mesial molar occlusion was greater in the preterm group. The incidence of bilateral symmetrical canine relationship was the same in both preterm and control groups, but inside the preterm group the girls had better symmetry than the boys. The findings of this research suggest that short gestation is not associated with reduced permanent and deciduous tooth crown dimensions in prematurely born children and also confirm the presence of the sexual dimorphism in tooth crown size. The studies also indicate that the clinical tooth eruption is accelerated in all observable permanent teeth in prematurely born children. The findings of occlusal morphology indicated that premature birth may effect the sagittal occlusal development. General health condition, neonatal and postnatal factors like intubation, postnatal molding of head shape and the importance of catch-up growth and early functional activity should be considered as possible influencing factors. Preterm birth may also interfere with the development of symmetry and lateralization.