Medicine Theses

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This collection is made up of doctoral and master theses by research, which have been received in accordance with university regulations.

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Now showing 1 - 5 of 33
  • Publication
    An Investigation into the Impact of Maternal Dietary Intakes, Well-being and Breastfeeding on Longitudinal Child Health
    (University College Dublin. School of Medicine, 2022) ;
    0000-0002-6979-756X
    Pregnancy is a unique time in that the health and behaviour of one individual can have a lasting impact on the offspring, from infancy through to adulthood. Therefore, understanding maternal health factors during pregnancy and how they underpin offspring health is critical. This thesis uses data from 3 studies carried out during pregnancy; the ROLO longitudinal birth cohort study, the PEAR Study, and the MicrobeMom trial, to explore maternal health factors and their impact on infant and child health using cohort analysis. Maternal well-being was overall found to be reduced in early pregnancy. Increased maternal dietary intakes during pregnancy of fibre, magnesium and B vitamins were noted to be associated with increased maternal well-being. This may be facilitated by the beneficial effect of fibre on the gut-brain axis. It was interesting to note that maternal well-being was not associated with breastfeeding practices. Despite low well-being during pregnancy, mothers are still breastfeeding. Considering the low rates of breastfeeding, specifically in Ireland, it is important that modifiable risk factors for breastfeeding are addressed. Fetal growth is a complex, dynamic process that requires appropriate modelling. This work used growth trajectories of offspring from 20 weeks’ gestation until 5 years of age, which appropriately modelled longitudinal offspring growth. Blood lipid profiles in early and late pregnancy, and adherence to national dietary allowances, were not found to be associated with offspring growth in our cohort which featured predominantly infants with an average birthweight of 4.1 Kg. Modelling fetal and infant growth appropriately is essential to further understand how the maternal environment can alter offspring growth and development. Microbial dysbiosis may play a role in the development of obesity. Infant gut microbiome diversity at 1 month of age was assessed using alpha and beta diversity, determined using metagenomic shotgun sequencing. This research did not find any association between probiotic supplementation during pregnancy or dietary intakes and offspring gut health. However, well-being in late pregnancy and breastfeeding practices at 1 month postpartum were found to be beneficial for improving infant microbial diversity. Breastfeeding initiation and breastfeeding duration were also found to be associated with healthy eating behaviours in children at 5 years of age, as were maternal eating behaviours. Encouraging healthy breastfeeding practices is paramount for improving health outcomes of offspring. This thesis provides novel insights into maternal health factors that shape the pregnant environment, and how these may influence offspring health and play a role in childhood obesity. Public health policy should prioritise maternal mental health and dietary intakes, as well as encouraging women to continue with prolonged breastfeeding. Unique opportunities for intervention during pregnancy are presented. The importance of longitudinal follow-up studies after pregnancy and the use of cohort analysis to define correlations that can inform future clinical trials is explored. Optimising the health of mothers is crucial to improve long-term health outcomes of future generations.
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  • Publication
    Fertility Preservation in Young Women at Risk of Ovarian Insufficiency due to Malignancy or Endometriosis
    (University College Dublin. School of Medicine, 2022) ;
    0000-0003-3684-6860
    Advances in science have afforded women the opportunity to avail of resources which has the potential to prolong their reproductive lifespan. Unfortunately predicting those who may need fertility preservation most, is not always feasible. We identified two cohorts of women, potentially at high risk of impaired ovarian reserve and therefore could benefit most from availing of assisted reproductive therapy (ART), including fertility preservation, with the potential to mitigate the negative fertility consequences of their underlying conditions and prevent unintended childlessness. The research presented in this study takes us firstly through the implementation and development of the first National Program for fertility preservation services for female adolescents and young adults with cancer, and for female survivors of childhood cancer in Ireland. We describe the processes navigated to provide an essential fertility counselling, surveillance and assessment service for this vulnerable cohort of survivors. A service which should be provided as standard by the Health Service Executive in Ireland, to match the standards of care available across Europe and in the U.K. We then present our work which explored doctors attitudes and practices in the management and optimisation of fertility in women with moderate to severe endometriosis and endometriomas, and our findings on how these patients described their experienced of the care and counselling they received as part of the surgical management of endometrioma, moving on to the assessment of ovarian reserve in women who have undergone surgery for endometrioma. Finally through the analysis of RNA sequencing studies, we sought to further the knowledge of potential biomarkers of oocyte quality and competence in women with endometriosis. The identification of such biomarkers, in either the form of differentially expressed genes or enriched biological pathways aims to provide potential therapeutic targets in the treatment of endometriosis related sub-fertility, and aid in providing a personalised and individual approach to their care, specifically those undergoing ART. The findings presented in this thesis have built upon the growing body of evidence that fertility preservation resources should be available, and discussed with women who are at risk of impaired fertility due to current or prior history of malignancy, or benign diseases such as diagnosis of moderate to severe endometriosis, and in particular endometrioma which are known to negatively impact upon fertility. An individualised approach to fertility assessment, optimisation and prioritization should be strongly considered as the standard of care for women with endometriosis, particularly with endometriomas. For endometriosis, and other diseases which we know can negatively impact future reproductive capacity, such as treatment with gonadotoxic therapies, fertility preservation should be considered and included in pre-treatment counseling for those who have not yet completed their family, and for young girls undergoing gonadotoxic therapies who can be afforded a short window of time to avail of this. We believe the education of doctors working with young women with cancer, and those caring for women with moderate to severe endometriosis, will lead to an improvement in the dissemination of knowledge of, and uptake in and accessibility of these specialised services in those who need them most. Going forward, the identification of a clinical biomarker for oocyte quality and oocyte developmental competence, particularly in women with endometriosis will further streamline the approach to and counselling for fertility preservation procedures for this cohort of women. The mechanisms leading to poor oocyte quality remain largely unknown and multifactorial, as such, the identification of pathways or genes that might shed further light on this topic is hugely beneficial, and will facilitate essential advances in the world of ART.
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  • Publication
    Preparing for Group B Streptococcus Vaccine: Global perspectives on maternal immunisation
    (University College Dublin. School of Medicine, 2022)
    There are vaccines in clinical trials that target the bacterium Group B Streptococcus (GBS). Group B Streptococcus is a leading global cause of sepsis and meningitis in young infants. GBS is estimated to cause nearly 100,000 newborn deaths and 50,000 stillbirths per year globally, and GBS infection is an important cause of long term neurodisability. Group B Streptococcus vaccines are intended to be given to pregnant women to prevent infection in their infants. The success of any vaccine will depend on its uptake in the target population. Experience with prior maternal vaccines, e.g. influenza and COVID-19 vaccines, teaches us that acceptance of vaccines, especially if novel, is challenging for pregnant women. The objective of this thesis is to identify potential facilitators and barriers to acceptance of a future antenatal GBS vaccine across different healthcare settings. Research in three countries; the United States (US), Ireland and the Dominican Republic (DR) investigates how current maternal immunisation practices and approaches to GBS management during pregnancy may influence how a GBS vaccine might be accepted and integrated into routine antenatal care in different regions. I present the results of four studies: i) a narrative synthesis of the global literature on facilitators and barriers to maternal immunisation ii) a mixed methods survey and discrete choice experiment with 502 pregnant women in the US and Ireland iii) a survey with 300 pregnant women in the DR, and iv) a multicentre qualitative study with 70 maternity care providers in the US, Ireland, and the DR. Knowledge of GBS was poor among pregnant women in all three countries, 53% of US women, 30 % of Irish women and 1.7 % of DR women reported both an awareness and understanding of GBS. Pregnant women placed most importance on perceived infant benefit and provider endorsement when considering a future GBS vaccine. Among health care providers interviewed, there was variability in knowledge and beliefs pertaining to GBS, maternal vaccines and approaches to vaccine communication. Knowledge and beliefs differed by country and by provider type and impacted strength of provider endorsement of maternal vaccines. When considering novel vaccines, such as a GBS vaccine, pregnant women will be guided by their maternity care providers. However, this guidance may vary between providers. Taken together the results in this thesis highlight an urgent need for the inclusion of vaccinology, including content, specifically related to maternal immunisation, in the undergraduate, postgraduate and professional competence training of all healthcare professionals caring for pregnant women.
      27
  • Publication
    High-fibre diet affects gut microbiome and prevents the development of hypoxia-induced pulmonary hypertension
    (University College Dublin. School of Medicine, 2022)
    Pulmonary hypertension due to chronic lung diseases, including chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis, is one of the major causes of death worldwide. This pathology is characterised by structural changes in the pulmonary vasculature and sustained vasoconstriction. Treatment options for pulmonary hypertension are based on the regulation of vascular tone but does not demonstrate high efficacy and new ways for controlling disease are needed. Little is known about the role of the gut microbiota and their metabolites in the development of pulmonary hypertension. Recent studies demonstrated that systemic hypertension can be attenuated by gut microbiota intervention. Gut microbes can promote the development of systemic hypertension and can also be a therapeutic target to reduce blood pressure. The aim of this study was to determine if modification of the gut microbiome using a diet that is rich in soluble fibre could prevent the development of hypoxia-induced pulmonary hypertension. The high-fibre diet decreased adverse pulmonary vascular remodelling and decreased right ventricular systolic pressure in mice exposed to hypoxia. These changes were associated with increased abundance of short chain fatty acid-producing bacteria in the gut. Further analysis showed that soluble fibre consumption affected lung myeloid cell populations that were previously recognised as important players in the pathogenesis of pulmonary hypertension. Untargeted proteomic analysis of the right ventricle and the lungs revealed potential molecular pathways that may be affected by soluble fibre supplementation. In the right ventricle these pathways were associated with cardiac hypertrophic changes and glucose metabolism. Diet-induced alterations in inflammatory pathways and pathways related to vessel remodelling were found in the lungs of experimental mice. These data demonstrate for the first time that a high-fibre diet can act on the gut microbiome in the mouse model of hypoxia-induced pulmonary hypertension and prevent disease progression. Soluble fibre can significantly supress structural vascular remodelling and affect pulmonary immune system similar to previous published studies that were obtained in models mimicking left ventricular and systemic circulation dysfunction. Supplementation with high fibre diet could be considered as a supportive lifestyle modification for patients with pulmonary hypertension or subjects that have a high risk of pulmonary diseases.
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  • Publication
    Sex differences in the pulmonary microvascular endothelial responses to hypoxia under physiological shear stress
    (University College Dublin. School of Medicine, 2022) ;
    0000-0003-0842-2526
    Chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), are commonly complicated by the development of pulmonary hypertension (PH), which significantly increases the morbidity and mortality. Sexual dimorphism exists in PH. Females with PH due to lung diseases and/or hypoxia have higher pulmonary vascular resistance than males. However, females have better survival with PH than males. Recent studies suggest that sex hormone independent mechanisms contribute to the protection of males from the development of pulmonary arterial hypertension. However, it remains unknown whether sex hormone independent mechanisms contribute to the sex bias in PH due to lung diseases and/or hypoxia. Pulmonary endothelial cells play a crucial role in the pulmonary vascular remodelling and vasoconstriction in the response to hypoxia. Commonly, endothelial cell responses are studied in vitro in static conditions, i.e., without flow-induced shear stress. However, in vivo endothelial cells constantly experience shear stress, which regulates endothelial cell phenotype and function. The aim of the studies reported in this thesis was to examine the sex differences in the responses of human pulmonary microvascular endothelial cells (HPMEC) to hypoxia, cultured under physiological shear stress, that are independent of the sex hormone environment. In order to expose HPMEC to the hypoxic environment in the conditions of physiological shear stress a novel approach was established. In these conditions sex differences between male and female HPMEC were identified on the RNA and protein levels. Endothelial to mesenchymal transition was higher in female cells and proliferation rate was higher in male cells. The identified sex different pathways might contribute to the sex bias in pulmonary hypertension.
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