Philosophiae Doctor - PhD / In the 20th century, where tobacco smoking continues to be the leading preventable cause of death, an alarming number of people continue to smoke, despite awareness of the implications of exposure for themselves and those around them. Campaigns for the promotion of effective tobacco legislation and awareness are continuously being confronted by the tobacco industry's reluctance to put the health of their consumers before company profits, leading to a ripple effect of misinformation, serious health risks and economic implications, at least for the consumers. Pregnant women are especially a concern, because exposure to tobacco smoke affects not only the smoking mother but has serious implications for the health of her unborn child. Therefore, the aim of this study was to investigate the effect of maternal exposure to nicotine during all the phases of lung development, or from the onset of the phase of rapid alveolarisation and, whether copper supplementation will prevent the adverse effects of maternal nicotine exposure, on lung development in the offspring. / South Africa

This resource list is a starting point before working with a mentor in the specialized area of neonatal physical therapy practice.

Bronchopulmonary dysplasia (BPD) is diagnosed in approximately 40% of extremely preterm infants, those born before 28 weeks’ gestational age, and affects roughly 10,000 to 15,000 infants annually in the United States alone. Current treatment of BPD aims to not only aid in the survival of the infant but to also minimize further lung damage and promote physiologic growth to enhance lung development and repair. As the pathogenesis of the disease is multifactorial, including pre-, peri-, and postnatal factors, treatment and prevention approaches to BPD are diverse and include both medical treatment and ventilation strategies. Late postnatal steroids (> 7 days of life) have been proven to facilitate extubation and reduce the incidence of BPD in preterm infants. However, there is evidence that the use of steroids may contribute to increased rates of neurological impairment, including increased incidence of cerebral palsy. Given these findings, the American Academy of Pediatrics (AAP) guidelines recommend against the routine use of systemic steroids in the prevention of BPD and instead argues its use should be limited to infants who are considered extremely high-risk. The aim of this study is to determine whether the use of postnatal dexamethasone decreases the risk of developing BPD in a subset of high-risk infants, those with a concomitant diagnosis of necrotizing enterocolitis or late onset sepsis. A sample size of 200 extremely preterm infants with either necrotizing enterocolitis (NEC) and/or sepsis will be enrolled in a multi-center double-blinded randomized controlled trial comparing a low-dose dexamethasone taper and saline placebo. Infants will be evaluated for the development of BPD based on respiratory support and supplemental oxygen requirement at 36 weeks’ post-menstrual age (PMA). Infants will also be evaluated for presence of neurodevelopmental outcomes at 18- to 22-months follow-up. The results of this proposed study will build the evidence base for the safety and efficacy of postnatal steroids in the prevention of BPD in a subset of high risk, extremely preterm infants. This will help to establish a more detailed characterization of infants for which the benefits of steroids outweigh the risks. The results will enable clinicians to make more informed decisions regarding the medical care of extremely preterm infants and more accurately counsel parents on the incidence of subsequent BPD development, as well as long-term morbidities.

Background: Extrauterine growth restriction (EUGR) is multifactorial in etiology and predisposes infants to multiple morbidities that can be significantly ameliorated by adequate nutrition and appropriate longitudinal growth. Current strategies to reduce the risk of EUGR include optimization of parental nutrition, varying schedules of feeding advances, and caloric supplementation. Very low birthweight (VLBW) preterm infants are particularly affected by EUGR, therefore ensuring adequate postnatal growth is an essential component in improving the long-term health outcomes for VLBW infants. The objectives of this observational study were to examine potential risk factors for growth failure among premature infants that did not respond to caloric and volume supplementation. Methods: We conducted a retrospective chart review of all infants born at the University of Massachusetts level III NICU from January 2016 to June 2020. Growth was tracked using PediTools electronic gestational age and growth calculators. (17) We reviewed the EMRs of infants who met the criteria for EUGR at the time of hospital discharge for a variety of potential factors affecting growth. Results: Overall, a total of 448 infants were screened with a final study cohort of 358 infants, of which 13% were discharge with EUGR. Analysis of demographic and clinical characteristics of infants with EUGR before and after nutritional intervention showed no statistically significant differences between the two cohorts. Pre-protocol, only weight percentiles and z-scores were statistically significant. Post-protocol, the change in z-score was also statistically significant. The only factor found to be statistically significantly different between was Necrotizing enterocolitis (NEC). Timing of EUGR in the pre-protocol groups occurred between 33-35 weeks, while in the post-protocol group EUGR occurred between 32 and 37 weeks (Figure 2). Conclusions: Our findings confirmed the presence of several factors that have been previously shown to increase risk for EUGR, including male sex, lower gestational age, lower birth weight, and the occurrence of NEC. It also identified an additional risk factor, that of being born “constitutionally small”. In the post-protocol cohort, the change in z-score was statistically significant in addition to birth weight percentile and z-score and discharge weight percentile in z-score. The window in which EUGR occurred as well as the interquartile range was significantly widened post-protocol. These data suggest that the volume supplementation protocol successfully addressed the causes of EUGR in some infants, but other mechanisms may have occurred in infants who were still discharged with EUGR post-protocol.

This research examines the structure of the NICU (neonatal intensive care unit), a venue that juxtaposes a highly technological and medical setting against the care and nurturing of child by her parents. In this site, parents must construct and refine their definition of what it means to be a good parent in the context of the environment, medical professionals' expertise, and their child's hospitalization. At the same time, the health professionals on the unit are also impacted by their own experiences, preconceptions, and faith in medicine. Particularly relevant actors are the registered nurses, who care for babies but interact with parents; how nurses conceive of the parenting role influences the nature of this interaction, and therefore the experience of the parents in the unit. Yet nurses' definition of good parenting in the NICU often contradicts that of parents, and those who fail to meet the nurses' definition may find themselves labeled bad parents. Data for this research was collected in two urban NICUs. Mixed qualitative methods were used in the form of participant observation and in-depth interviews with both parents and staff members at both institutions, to the end of uncovering themes regarding commonalities of characterizations of good and bad parenting. Findings demonstrate that in constructing a definition of good parenting, parents medicalized themselves in the context of the NICU. Many incorporated medicalization into the parental role by accepting the notion that they could help to heal their baby, not just through care work but by actively taking on responsibilities that they felt could be beneficial. Parents' definitions of good parenting also included relying on the opinions of medical experts, which demonstrated a faith in the professionalization of medicine and the medicalization of childbirth and child care. Nurses' conceptions of what made up a good parent included deference. Many believed that parents needed to do what was best for the baby, defining this in part by stating that it meant listening to the experts, including themselves. Taking a Foucauldian approach to examine the position of nurses in the hospital, this fulfilled a need many nurses had to be respected for their skills and feel powerful on the unit. Additionally, nurses would label those whom they did not feel were meeting their parameters for being a good parent as bad parents, which often involved judging parents on the basis of their actions before or during their pregnancy. Parents were also judged based on how they acted in the unit. The bad parent label was applied both to parents who had confidence in their own abilities to parent while in the NICU, and also to mothers with a history of drug abuse. In accordance with labeling theory, once this label was affixed, it impacted the way that nurses and other staff treated parents and viewed all of their activities. The recent nature of this work reflects the impact of the newest technological innovations on the parental experience. This includes the increasingly sophisticated medical equipment in the NICU, what this has meant in terms of pushing the limits of viability, and the ability of parents to access information via the Internet. It also demonstrates the gap in parents' and nurses' ideas in the NICU, validating the place of sociology in discussions of family-centered care. / Sociology

Thermoregulation is considered a top priority in neonatology due to the fact that relative to adults, neonates have a morphological susceptibility to excessive heat exchange with the environment, and exhibit limited physiological/behavioural responses to thermal strain. Consequently, the environmental conditions in which they are nursed must be tightly regulated to maintain body temperature stable. Neonatal intensive care units (NICU) use radiant warmers (RW) to thermally manage many newborns. However, recent evidence suggests that RW induce intermittent bouts of thermal strain that could adversely affect patients. This warrants further investigation of neonatal heat balance and the pertinent factors affecting it. Conducting an exhaustive audit of heat exchanges affecting the body during standard care under a RW could yield important information that would lead to the improvement of clinical practice in NICUs. The present thesis focuses on neonatal thermoregulatory responses, various body heat exchange mechanisms and processes during standard care under RW.

Worldwide, more than 1 million infants die as a result of premature birth. In the United States, where 1 in 10 births occurs preterm, premature birth is the leading cause of infant mortality. Premature infants have high rates of mortality and morbidity, with the highest rates seen in those infants born extremely preterm -- prior to 30 weeks gestation. Severe morbidity in these infants often contributes to life-long health problems. Maternal hypertension (HTN) is one contributor to preterm birth and also contributes to fetal growth restriction, resulting in birth weights which are small for gestational age (SGA, and generally within the lowest 10th percentile). Within this high risk population, SGA infants have increased risk of mortality compared to appropriate for gestational age infants. Therefore the impact of maternal HTN on neonatal outcome might be presumed to be negative. Previous studies however, have been contradictory, with both higher and lower rates of infant mortality reported in infants born to mothers with HTN, as well as differing reports analyzing the relationship between serious morbidity and maternal HTN. Utilizing the Vermont Oxford Network Very Low Birth Weight database, a collaborative database of Level III Neonatal Intensive Care Units across the world, 88,275 North American infants born between 22+0 and 29+6 weeks gestational age between 2008 and 2011 were identified. This dissertation explores the relationship between maternal HTN and gestational age at time of birth within this population, and the reported rates of morbidity and mortality in infants born prior to 30 weeks gestation. The independent contributions of maternal HTN with neonatal morbidity and mortality in our population were estimated using logistic regression and adjusting for factors previously known to be associated with risk, including birth weight, antenatal steroid exposure, infant sex, maternal race/ethnicity, prenatal care, inborn/outborn status, and birth year. We hypothesized that mortality rates would be lower for infants born to mothers with HTN compared to those born due to other factors, when corrected for the noted confounding variables and surviving infants would have better prognoses, as evidenced by lower rates of severe morbidity, including bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, and infection. Within the higher-risk SGA population, we hypothesized that mortality rates would be higher than observed in appropriately grown infants, but decreased in those born to mothers with HTN, despite the association between maternal HTN and SGA. This dissertation begins with an explanation of current knowledge about preterm birth, maternal HTN, and their associations. Chapter 2 focuses on the relationship between maternal HTN and infant mortality in extremely preterm infants. Chapter 3 examines the risk associated with severe morbidities in surviving infants. In addition, we also use a combined morbidity risk assessment score which has previously been used to determine future risk of long term disability. In Chapter 4, SGA infants are separately evaluated for their risk of mortality and the association with maternal HTN. These analyses support the high mortality and morbidity rates seen in extremely preterm infants. Maternal HTN, after adjustment, results in reduced risk of both mortality and severe morbidities in infants compared to infants born to mothers with other underlying contributors to preterm birth. This suggests that clinical practices and parental counseling should reflect differing risk profiles in sub-populations of extremely preterm infants.

Orientador: Simone Biagio Chiacchio / Resumo: A bubalinocultura tem assumido cada vez mais importância econômica devido às suas características zootécnicas como a rusticidade e melhor qualidade do leite para a fabricação de derivados lácteos quando comparada ao leite de vaca. A morte embrionária e fetal é um importante fator de diminuição da eficiência reprodutiva pois aumenta o intervalo entre partos e causa perdas econômicas pela diminuição da lactação. O eletrocardiograma materno-fetal permite a avaliação da frequência cardíaca fetal (FCF) e variabilidade da frequência cardíaca (VFC) mediante análise de indicadores da VFC (HR, RR, RMSSD, SDNN, LF, HF e a relação LF/HF). Foram avaliadas semanalmente nove búfalas e neonatos saudáveis da raça murrah, nos momentos -28, -21, -14, -7 dias antes do parto e nos dias 7, 14, 21 e 28 dias após o parto. Nas búfalas foi observada diferença significativa na frequência cardíaca na fase pré-parto e com diminuição gradual conforme proximidade do parto. Já os índices RMSSD e SDNN não apresentaram diferença significativa mas demonstraram predomínio parassimpático. O componente de baixa frequência (LF) apresentou aumento significativo na fase pré-parto e o componente de alta frequência (HF) apresentou diminuição significativa, compatível com predomínio simpático. Embora não significativa, a relação LF/HF apresentou aumento na fase pré-parto e equilíbrio vagal pós-parto. Já os bezerros apresentaram variação significativa na fase pré-parto, com aumento gradativo conforme a proximidade dest... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Bubalinoculture has become increasingly important economically due to its zootechnical characteristics such as the rusticity and better quality of milk for the manufacture of dairy products when compared to cow's milk. Embryonic and fetal death is an important factor in decreasing reproductive efficiency because it increases the interval between births and causes economic losses due to decreased lactation. The maternal-fetal electrocardiogram allows the assessment of fetal heart rate (HRF) and heart rate variability (HRV) by analyzing HRV indicators (HR, RR, RMSSD, SDNN, LF, HF and the LF / HF ratio). Nine murrah buffaloes and healthy newborns were evaluated weekly at -28, -21, -14, -7 days before delivery and at 7, 14, 21 and 28 days after delivery. In buffaloes, a significant difference in heart rate was observed in the pre-partum phase and with a gradual decrease as the childbirth approached. The RMSSD and SDNN indices did not present significant difference but showed a parasympathetic predominance. The low frequency component (LF) showed a significant increase in the prepartum phase and the high frequency component (HF) showed a significant decrease, compatible with sympathetic predominance. Although not significant, the LF / HF ratio showed an increase in the prepartum phase and postpartum vagal balance. Calves, on the other hand, presented significant variation in the pre-partum phase, with gradual increase according to its proximity, with subsequent postpartum fall. Th... (Complete abstract click electronic access below) / Mestre

Com o objetivo de avaliar os parâmetros clínicos e zootécnicos dos efeitos da substituição do leite in natura por colostro na alimentação de bezerros até 60 dias de vida, foram utilizados bezerros machos Holandeses, do nascimento aos 60 dias de vida. Os animais, em número de 24, foram trabalhados dentro de um delineamento em blocos casualizados, formando-se quatro blocos de seis animais, com repetição dentro de blocos, para atender a três tratamentos. Os blocos foram formados com neonatos, cuidando-se para que a diferença de idade dentro de bloco não superasse 21 dias. Os tratamentos compreenderam em misturas iniciadoras idênticas e feno de coast cross, fornecidas desde a primeira semana de vida, e leite mais colostro nas seguintes formas: Grupo 1, colostro diluído em água na proporção 2:1 até os 60 dias de idade, Grupo 2, colostro diluído em água na proporção 2:1 até os 30° dia de idade e leite in natura do 30° ao 60° dia, Grupo 3, leite in natura até os 60° dia de idade. Todos os animais receberam colostro materno (4,0 kg por animal/dia) durante os três primeiros dias de vida. Amostras de sangue foram colhidas nas idades de 0, 24, 48, 72 horas, 5° dia, 7° dia, 15° dia, 30° dia, 60° dia para avaliação do proteinograma. Semanalmente foi executadas pesagens para avaliar ganhos de peso. Não foi encontrado nos diferentes tratamentos alterações significantes no proteinograma e ganho de peso dos animais. Conclui-se que a diluição de colostro nos tratamentos estudados é viável na alimentação dos bezerros. / In order to evaluate clinical and zootechinical effects of the use of diluted colostrum as maternal milk replacement on Holstein Friesian calves feeding on the first 60 days of life, twenty four new born male calves were enrolled and randomly allocated on 4 blocks of six animals, with repetition of blocks in order to attend to three treatments. Animals from the same block should not have more than 21 days of age difference. Treatments consisted on starter mix, coast cross hay and liquid diet presented as: Group 1 diluted colostrum on water (2:1) for 60 days; Group 2 diluted colostrum on water (2:1) until 30 days and milk from 31 to 60 days, and Group 3 milk for 60 days. Blood samples were collected on 0 h, 24 h, 48 h, 72h and on days 5, 7, 15, 30, and 60 in order to evaluate serum protein. Weight gain and was evaluated every weekly. Solid and liquid intakes were evaluated daily. No significant difference was found among the treatments for serum protein and weight gain. Therefore, the colostrums dilution is viable option on calf feeding.

Com objetivos de validar o modelo de anóxia neonatal apresentado e analisar a distribuição de neurônios imunorreativos à proteína Fos (IR-Fos) no encéfalo de ratos neonatos submetidos ao insulto anóxico, foram utilizados 24 ratos wistar neonatos machos divididos em dois grupos: Anóxia (n=12) e Controle (n=12). O grupo Anóxia apresentou decréscimo de 75% no valor da saturação periférica de oxigênio durante a exposição ao nitrogênio, enquanto o Controle não apresentou alterações nos valores (97%±0,5). A análise do número de células IR-Fos mostrou ativação de áreas encefálicas relacionadas ao controle da respiração, estruturas límbicas e núcleos da rafe. Tais dados sugerem que o modelo experimental de anóxia neonatal utilizado é eficiente em produzir privação temporária de oxigênio em ratos neonatos, levando a respostas condizentes com a anóxia. Espera-se, com estes resultados, facilitar a compreensão dos eventos relacionados à neurodegeneração e neurorregeneração após anóxia neonatal e, se possível, abrir caminho para novas abordagens e perspectivas terapêuticas. / The aim of this study is to validate the experimental model of neonatal anoxia and evaluate by Fos imunoreactivity (Fos-IR) the effects of anoxic insult. Twenty-four male wistar neonates (weighting 6-8g) were divided in two groups: Anoxia (n=12) and Control (n=12). The anoxic group presented decrease of 75% in the value of the peripheric saturation of oxygen during exposure to the nitrogen while control group did not present alterations in the values of the peripheric saturation of oxygen during the studied time (97 % ± 0,5). These data suggest that the experimental model of neonatal anoxia presented is efficient in producing temporary deprivation of oxygen in neonates rats, leading to responses that characterize anoxia. Fos-IR neurons analisis showed important activation of respiratory regions, limbic strutures and raphe nuclei in anoxic group when compared to control group. We hope facilitate the understanding of neonatal anoxia neurodegeneration and neuroregeneration and possibly contribute for new approaches and therapeutic perspectives.