Neonates are more susceptible to influenza virus infection than adults, resulting in increased morbidity and mortality as well as delayed clearance of the virus. Efforts to improve influenza infection outcomes in neonates typically center on prevention, although current vaccines fall short of complete protection and can only be administered in humans after 6 months of life. We propose that as the neonatal immune system responds differently than the adult immune system, interventions that are efficacious or tolerable in adults cannot be guaranteed to perform the same in neonates. T cell vaccines that target conserved influenza virus epitopes have been proposed for conferring protection to multiple influenza virus strains, but if T cell vaccines will be used in infants and adults, neonates must be able to respond to the same T cell antigens as adults. Mouse pups responded to influenza virus peptide PA224-233 but not NP366-374 during influenza virus infection in contrast to the codominant adult response. Mice infected as pups also generated diminished T cell memory compared to mice infected as adults and displayed skewed immunodominance during secondary infection. Adult bone marrow derived dendritic cells (BMDCs) improved viral clearance when loaded with influenza virus and promoted NP366-374-specific CD8+ T cell responses in infected pups. BMDC peptide vaccination could stimulate PA224-233-specific but not NP366-374-specific CD8+ T cell responses in pups, but, PA224-233 vaccination offered no protection to pups during lethal infection. These data suggest that altered immunodominance must be considered when stimulating CD8+ T cell responses in adults and neonates. Immaturity and active suppression of immune responses are both factors in neonatal vulnerability to disease. Specifically, active suppression of neonatal immunity by regulatory T cells (Tregs) has been proposed as a driving factor in diminished neonatal immunity, but removing these cells can compromise viral defense or increase deleterious inflammation. Mice that lacked Tregs displayed compromised anti-influenza antibody responses and decreased lymph node responses during influenza virus infection. A high proportion of pup Tregs also expressed Gata3. Transgenic pups with a Treg specific Gata3 knockout displayed an increase in Tbet expression in both conventional and regulatory T cells and an increase in IFNγ producing CD4+ T cells in the lungs during infection. These data suggest that Tregs are required for effective humoral responses to influenza virus and that Gata3 expression influences Treg suppressive function in neonates.

Class of 2012 Abstract / Specific Aims: The objective of this study is to evaluate and compare clinical outcomes and economic impact involved with the use of beractant (B) compared to poractant (P) for the treatment of respiratory distress syndrome (RDS) in premature neonates admitted to a neonatal intensive care unit. Methods: Patients were included if they were less than 35 weeks gestational age at birth, survived at least 48 hours, and admitted to the neonatal intensive care unit and treated with P or B for RDS. The primary outcome of this study is the change in the fraction of inspired oxygen (FiO2) over the first 48 hours after surfactant administration. Secondary outcomes were the change in oxygen saturation, time spent on mechanical ventilation and continuous positive airway pressure (CPAP), complication occurrence and mortality of the neonates. Main Results: There were a total of 40 neonates whose charts were reviewed (n= 13 and n=27 in the P and B groups respectively). The mean gestational age of the neonates were 29.2+/-2.9 and 28.8+/-2.9 weeks in the P and B groups respectively. The FiO2 was found to not be lower between the P and B groups (35.5+/-22.2 and 42.4+/-24.2, respectively; p=0.379), as well as the O2 saturation (94.6+/-4.6 and 92.3+/-6.1; p=0.194). Significance was also not found for the other clinical or economic outcomes assessed in this study. Conclusions: There was not a significant difference between poractant and beractant in FiO2, O2 saturation, or in the other clinical outcomes evaluated in this study.

Objectives: Transitions of care (ToC) for a high-risk neonatal population, and in some cases inappropriate and early discharge, can have important implications for community and broader population health. As it is a key indicator of the efficiency of the system of health services, the ease of ToC has been a priority for improving care outcomes across all settings in our nation’s healthcare system. Research shows that inappropriate discharges can lead to negative outcomes for patients and their families, health professionals, and the health system. Collaboration amongst the health care professionals, the community, and the patient’s family is needed for an efficient transition. This research examined how interprofessional collaboration (IPC) can act as a catalyst for efficient and effective ToC from a high-risk neonatal unit to care back in the community. Approach: Twelve infants were observed from their admission on the Neonatal Intensive Care Unit (NICU) until their discharge home. The 12 consisted of four patients discharged directly home, four to another unit within the same hospital, and four to another institution. Stage one involved a document analysis of documents related to ToC policy on the NICU. Stage two involved observation. Stage three involved interviews with healthcare professionals (HCPs) in the hospital and community (n=30) and family members (n=12). Stage four consisted of deliberative workshops with the hospital management and research participants to share the results and obtain their feedback. Results: Including parents early in the ToC planning process helps parents feel they’re a part of the interprofessional care team, in-charge of their infant’s care and thus better equipped mentally to handle their infant’s ToC. Knowing early on their infant’s discharge plan allows parents the opportunity to ask questions regarding caring for the infant at home or to meet the new healthcare team at the new site (hospital/floor) prior to the transfer. Mechanisms need to be in place to ensure that communication regarding ToC is consistent and clear to and between all HCPs whether in the hospital (e.g. bedside nurse) or in the community (e.g. family doctor). Having a clear understanding of what information should be transferred during a ToC will prevent unnecessary tests and misunderstandings. Increasing HCPs’ knowledge of available community resources will aide in transitioning infants to community care and thus freeing bed space and decreasing unnecessary costs at the hospital (i.e. A feeding and growing baby can be weighed by family doctor or Rapid Response Nurse and not necessarily the neonatologist). A consistent ToC policy across all NICUs would also be beneficial to ensuring a smoother ToC of infants. Conclusion: It is believed that communication and education in an interprofessional context is critical for more efficient and effective ToC of neonates.

No description available.

Preterm infants are at risk for respiratory distress syndrome (RDS) due to immature lungs, leading to notable neonatal mortality. About 10% of US births are premature. While mechanical ventilation is a common RDS treatment, it can cause complications. If it fails, extracorporeal membrane oxygenation (ECMO) is employed, but standard ECMO devices are not suited for preterm babies. The limitations of hollow fiber membrane oxygenators used in ECMO have spurred interest in an artificial placenta that connects to the umbilical cord and supports lung growth. Microfluidic blood oxygenators, with their biomimetic designs, have being explored for this purpose. This thesis advances microfabrication techniques for Lung Assist Devices (LADs), focusing on two main objectives: I. Improving Throughput for Elevated Blood Flow Rates: This section delves into refining Microfluidic Blood Oxygenators (MBOs) to accommodate greater blood flow rates. By combining parallel units, we increased throughput and optimized LAD designs. Newly designed MBOs, with an expanded gas exchange surface area, can manage blood flow rates up to 60 mL/min. Using these enhanced MBOs, we constructed a novel LAD achieving superior oxygenation compared to predecessors. Our in vitro tests confirmed that this LAD can sustain blood flow rates of up to 150 ml/min, elevating oxygen saturation by approximately 20%—equivalent to an oxygen transfer of 7.48 mL/min, a leading figure for AP-type devices. II. Hierarchically Designed Microchannels: The second objective revolves around developing microchannels with a hierarchical layout to mitigate stagnation and high shear stress regions. Traditional photolithography poses challenges at channel intersections, inducing clotting risks. We pioneered alternative microfabrication methods, yielding diverse microchannels and intricate hierarchical designs that emulate natural vascular networks devoid of dead zones. These advancements have propelled the microfabrication domain for artificial placenta-like LADs. Utilizing our method, we produced channels varying from hundreds to a few microns in height with a single exposure and an opal diffuser. Thin membranes (~60 µm top and ~45 µm bottom) were amalgamated, culminating in a total depth of about 200 µm. Such oxygenators excel in oxygenating blood even at intense flow rates of up to 15 mL/min per unit. Leveraging these hierarchically designed MBOs, we crafted a LAD supporting a flow rate of 100 mL/min, offering an oxygen transfer of 5.21 mL/min. Both LADs developed in this research proficiently support premature neonates weighing up to 2 kg. Notably, the priming volume of the LAD using the enhanced MBOs has been substantially minimized, underscoring its advancements over earlier models. Realizing these objectives can transform neonatal care, addressing respiratory challenges in premature neonates and bolstering their chances for a healthier life. / Thesis / Master of Science (MSc)

No description available.

Thesis (MEng) -- Stellenbosch University, 2014. / ENGLISH ABSTRACT: The thermal regulation response of a neonate has to maintain temperature homeostasis, thus resisting the changes to core temperature caused by the unstable external environment. In this thesis a theoretical thermal regulation response model for human infants subject to a well-defined environment is presented. This model will aid in understanding the influences of environmental effects on core and skin temperature. The respiratory system was also included in the thermal regulation response model. A literature study was undertaken emphasising thermal regulation of neonates. The blood circulation system, skin tissue physiology and the respiratory system physiology were reviewed and helped to provide a better understanding of the thermal regulation mechanisms and how heat transfer theory can be used to analyse heat loss in neonates. The thermal heat transfer properties of skin tissue was specified and used in the development of the theoretical simulation model. The bioheat equation developed by Pennes was reviewed as well as a mathematical model developed by Fiala et al. The theoretical model was developed by applying the conservation of energy and the applicable properties to one dimensional layers to generate a set of time dependent differential equations. The set of equations was solved using an explicit numerical finite difference method, given the initial conditions. The mathematical model included heat loss through the skin, heat loss through the respiratory system, as well as the effect of environments (in incubator or in a bassinette) with different temperatures, relative humidity’s and air velocities. Clothing was also incorporated. A clinical trial was conducted to facilitate a better understanding of thermal stability in neonates. The data acquired during the clinical trial was also used to verify/validate the theoretical simulation model. The results from the simulation temperatures were compared with the average outer skin layer temperature measured during the clinical trial and an average deviation of only 0.22 °C was found, thereby proving that the simulation model gives realistic results. An experimental respiratory model was designed to simulate the respiratory system and illustrate the functioning thereof with regards to heat transfer. This was done by designing an experimental mechanical lung apparatus. The apparatus was tested and successfully imitated the respiratory system with regards to heat transfer. The results obtained from this experiment indicated that the trachea must be moistened continuously in order to condition inhaled air. The outcome of this project identified two possible applications. For the first application it can be used as a test tool for quickly evaluating the influence of different environmental conditions in the transient temperature distribution of neonates. The second application would be to enable medical professionals to monitor the influence of the thermal environment, including the temperature, relative humidity and air velocity, on the neonate’s temperature change to allow for a speedier thermal intervention strategy. / AFRIKKANSE OPSOMMING: Die hitte regulering reaksie van 'n pasgebore baba moet temperatuur homeostase handhaaf, en sodoende die veranderinge aan die kern temperatuur weerstaan wat veroorsaak word deur ‘n onstabiele eksterne omgewing. In hierdie tesis word 'n teoretiese hitte regulerings reaksie model vir menslike babas, onderhewig aan 'n goed-gedefinieerde omgewing, aangebied. Hierdie model sal help met die verstaan van die invloed wat omgewings effekte het op die kern en vel temperatuur. Die respiratoriese sisteem is ook ingesluit in die hitte regulering reaksie model. 'n Literatuurstudie is onderneem met die klem op hitte regulering van pasgebore babas. Die bloed sirkulasie sisteem, vel weefsel fisiologie en die respiratoriese sisteem fisiologie is hersien en help met beter begrip van die hitte regulering meganismes en hoe hitteoordrag teorie kan gebruik word om hitte verlies in pasgebore babas te analiseer. Die hitte-oordrag eienskappe van vel weefsel is gespesifiseer en word gebruik in die ontwikkeling van die teoretiese simulasie model. Die ‘bioheat’ vergelyking ontwikkel deur Pennes is hersien asook 'n wiskundige model wat ontwikkel is deur Fiala et al. Die teoretiese model is ontwikkel deur die toepassing van die behoud van energie tesame met die gebruik van toepaslike eienskappe en een dimensionele lae om 'n stel tyd afhanklike differensiaalvergelykings op te wek. Die stel vergelykings is opgelos met behulp van 'n eksplisiete numeriese eindige verskil metode, gegewe die aanvanklike toestande. Die wiskundige model sluit in die hitte verlies deur die vel, hitte verlies deur die respiratoriese stelsel, sowel as die effek van die omgewing (broeikas of in 'n bassinette) met verskillende temperature, relatiewe humiditeit en lug snelhede. Klere is ook in ag geneem. 'n Kliniese proef is gedoen om 'n beter begrip van termiese stabiliteit in pasgebore babas te fasiliteer. Die data wat tydens die kliniese proef verhaal is, is ook gebruik om die die teoretiese simulasie model te verifieer. Die resultate van die simulasie temperature is vergelyk met die gemiddelde buitenste vel laag temperatuur gemeet tydens die kliniese proef en 'n gemiddelde afwyking van slegs 0.22 °C is gevind, wat dus bewys dat die simulasie model realistiese resultate gee. 'n Eksperimentele respiratoriese model is ontwerp om die respiratoriese stelsel te simuleer en die funksionering daarvan te illustreer met betrekking tot hitte-oordrag. Dit is gedoen deur die ontwerp van 'n eksperimentele meganiese long apparaat. Die apparaat is getoets en slaag daarin om die respiratoriese stelsel suksesvol na te boots met betrekking tot hitteoordrag. Die resultate verkry uit hierdie eksperiment het aangedui dat die tragea kostant klam gemaak moet word om ingeasemde lug te kondisioneer. Die uitkoms van hierdie projek het twee moontlike toepassings geïdentifiseer. Die eerste is dat dit as 'n toets instrument vir die vinnige evaluering van die invloed van verskillende omgewingsfaktore in die temperatuur verspreiding van pasgebore babas gebruik kan word. Die tweede toepassing sal wees om medici in staat te stel om die invloed van die termiese omgewing te monitor, insluitend die temperatuur, relatiewe humiditeit en lug snelheid, om die neonaat se temperatuur verandering te monitor en voorsiening te maak vir 'n vinniger verwarmings intervensiestrategie.

The UK currently has the highest number of premature births (babies born before 37 weeks gestation age and below 2.5kg) in Europe affecting around 70,000 babies and their caregivers each year. Consequently many interventions have been created to support the development of the preterm newborn and minimise the complications of prematurity. Many of the interventions developed have been predominantly tactile and have almost exclusively focused upon their effect upon the baby and not, for example considered the effect that this type of intervention might have upon the parents; specifically the mother, when they are the ones who perform the therapy. In fact there is a severe lack of systematic studies investigating the latter. Hence, the aim of this thesis was to search for research-based evidence on the benefits of environmental support to both babies (e.g. increased weight gain or awake periods) and their mothers (e.g. higher perceptions of themselves as a mother) during hospital confinement and within the context of Neonatal Health Psychology (NNHP). For this reason, the main hypothesis investigated whether mothers’ cognitions and emotions; specifically Maternal Self-Efficacy, Self-Esteem and Attachment, would be affected by environmental mediators in the form of structured or non-structured tactile sensory nurturing interventions. The empirical work reported in this thesis is divided into 3 distinct phases. Firstly, as their was no appropriate measure of maternal Self-Efficacy for mothers of hospitalised preterm neonates the main aim of Phase-1 was to develop and validate an appropriate measure. Using a prospective survey method and a mixed design (between/within and correlational) a total of 160 mother-preterm dyads (pooled from 2 cohorts; cohort 1, N=100; cohort 2, N=60) were recruited. The results demonstrated that the Perceived Maternal Parenting Self-Efficacy (PMPS-E) tool had good initial psychometric properties (including internal/external reliability and construct validity) for its use with mothers of relatively healthy hospitalised preterm neonates. Secondly, in order to investigate mothers’ perceived maternal parenting self-efficacy beliefs further Phase-2 examined whether the type of feeding a mother chose to give to her baby mediated her self-efficacy beliefs. The results suggested that breastfeeding a preterm neonate during hospital confinement may adversely affect mothers’ perceptions of their efficacy in all aspects of parenting. Finally, using an experimental method Phase-3 tested the main hypothesis of this thesis and used a randomised cluster control trial (RCCT) design to allocate 60 mothers and their preterms equally to one of three cluster groups; consisting of either structured (e.g. TAC-TIC therapy or Using a Toy) or non-structured (Placebo/Control) tactile sensory nurturing interventions. The main findings illustrate that tactile sensory nurturing interventions do mediate maternal cognitions and emotions, preterm weight gain and behavioural state. In particular, mothers who performed TAC-TIC demonstrated significantly higher self-reported perceptions in their self-efficacy, self-esteem and attachment, which was attributed to the fact that these babies spent increased amounts of time in an alert and responsive behavioural state, and gained more weight throughout the study period. Thus, the work presented throughout this thesis has implications for Neonatal Health Psychologists and other Health Care professionals’ practice within neonatal units, the use of Neonatal Health Psychology as a framework to study the preterm neonate and their family, and also the way in which both mothers and their hospitalised preterm neonates are supported during hospital confinement.

The purpose of this dissertation is to explore potential barriers nurses experience in providing effective pain management for preterm and critically ill infants in neonatal intensive care units (NICUs). The specific aims of the study conducted are to examine (a) NICU caregivers’ knowledge about pain, (b) scales used to evaluate pain in infants, (c) NICU nurses’ documented pain practices, and (d) bias in treating pain of certain types of infants. This dissertation is comprised of three manuscripts. The first manuscript is an integrated review of the literature describing caregiver knowledge, barriers, and bias in the management of pain in neonates. The second manuscript is a systematic review of multidimensional pain scales developed for use in preterm and critically ill infants. The final manuscript reports a descriptive exploratory study designed to examine nurses’ knowledge of pain, knowledge of intensity and appropriate management of procedural pain, bias in treating pain of certain types of infants, and documented pain management practices. Over the past 25 years, caregiver knowledge of pain in preterm and critically ill infants has advanced from beliefs that neonates do not feel pain, to the knowledge that preterm infants experience more pain than term infants, older children, and adults. Nine multidimensional pain scales with varying levels of reliability and validity have been developed, yet a gold standard for pain assessment in preterm and critically ill neonates has not emerged. In this study, baccalaureate prepared nurses (BSN) and nurses with higher total years of nursing experience had better knowledge of pain in this population than associate degree nurses (ADN). However, pain management was inconsistent, resulting in pain that was untreated as often as 80% of the time. Nurses reported that physician practice was the primary obstacle to providing effective pain management. Additional concerns included knowledge deficits of nurses and physicians, lack of communication and teamwork, and rushed care. Nurses reported biases in managing pain and were less likely to invest time and energy treating the pain of infants experiencing neonatal abstinence syndrome.

Les nouveau-nés et jeunes enfants forment une population spécifique pour laquelle les études cliniques sont rares et difficiles à mettre en œuvre. La modélisation pharmacocinétique permet de réaliser des études non invasives et est donc particulièrement bien adaptée à cette population. Tout comme pour l'expérimentation scientifique qui nécessite plusieurs études pour conduire à un consensus, plusieurs bases de données pharmacocinétiques sont nécessaires afin d'arriver à un modèle optimal généralisable. Néanmoins, de nombreux modèles pharmacocinétiques sont publiés pour une même molécule, indépendamment les uns des autres, sans que l'on sache clairement lequel est le plus adapté. Inversement de nombreuses molécules ne sont pas ou peu étudiées et ne permettent pas de conduire à des recommandations fiables.L'objectif de ce travail de thèse était de rechercher une stratégie pour privilégier un modèle par rapport à un autre et ainsi, conduire à un modèle optimal permettant d'émettre des recommandations. Nous avons choisi de centrer notre intérêt sur les études pharmacocinétiques de population en néonatalogie et plus précisément sur deux molécules: la vancomycine et le phénobarbital. / Neonates and young infants are a specific population in which clinical studies are rare and difficult. Pharmacokinetic modeling allows to realize non invasive studies and is therefore particularly well suited for this population.As well as for scientific experimentation which requires several studies to lead to a consensus, several pharmacokinetic databases are needed to achieve a generalizable optimal model.Nevertheless, many pharmacokinetic models are published for the same molecule, independently of each other, without knowing clearly which is the most suitable. Conversely many molecules are not or little studied and can not lead to reliable recommendations.The aim of this thesis was to find a strategy to prefer a model over another, and thus lead to an optimal model to make recommendations. We chose to focus our interest on population pharmacokinetic studies in neonatology and more specifically on two molecules: vancomycin and phenobarbital.