The aim of this thesis was to strengthen understanding of self-reported sleep in pregnancy by drawing together evidence from: previously published research; de novo analyses of existing and novel datasets; and the lived experience of pregnant women themselves. This mixed- methods approach found that: a lack of standardisation and potential flaws in the design of previous studies do not yet permit a formal meta-analysis to be performed; and previous findings remain vulnerable to error and publication bias. The three de novo quantitative analyses of self-reported sleep conducted for this thesis sought to address many of the flaws in previous research. These analyses indicate that: several pre- existing/pre-pregnant sociodemographic and health characteristics contribute to the less favourable sleep commonly reported by pregnant women (as compared to age-matched non- pregnant women); and that variation in these and (un)related lifestyle and behavioural factors during pregnancy also contribute to variation in self-reported sleep amongst pregnant women. However, the last of these analyses provides evidence that variation in a commonly experienced phenomenon (glucose intolerance and, at its extreme, gestational diabetes) is associated with less favourable sleep in what appears to be a dose-response relationship. Analysis of posts to web-based forums by women with first-hand experience of sleep in pregnancy confirm that pregnancy-specific somatic changes were experienced/understood to be the principal causes of less favourable sleep; although the advice offered to others facing similar problems tended to focus on behavioural and situational factors as suitable avenues for intervention. On the basis of this evidence, it is clear that none of the self-administered sleep instruments/items available, and used, to-date are capable of comprehensively assessing the sleep of pregnant women. Future research must develop/use a dedicated sleep instrument to improve our understanding of the range, prevalence and likely determinants of the less favourable sleep more commonly reported by pregnant women.

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The liver is known to increase in size in the mouse during pregnancy; however, the mechanisms behind this are not fully understood. There are inconsistencies in the literature, which argue whether hyperplasia or hypertrophy is responsible. The aim of this thesis was to investigate the possible mechanisms and to explain some of the molecular processes, which bring these adaptations about. To address this, virgin female C57Bl/6 mice were mated and culled at 3 time points during pregnancy and their livers analysed. Non-pregnant, age matched mice were analysed as controls. Phenotypic measurements of the mice were taken in order to make sure the model represented known changes seen during mouse pregnancy. Haemotoxylin and eosin staining showed that there is an increase in cell size from day 14 of gestation. Staining for Ki67, a cell cycle marker, suggested that cell proliferation was also increased at day 14 and day 18 of gestation. This was further supported by gene expression analysis of Ki67 and cyclin B1. Transcriptome analysis was carried out on the livers at both day 14 and day 18 of gestation. Pathway analysis predicted an increase in cell proliferation at both time points and a decrease in apoptosis at day 18 of gestation. These pathways were further validated by analysis of a previously published array data set, showing the same pathway changes at all time-points measured. Gene expression of the apoptosis markers p53, Fasand Casp6 were used to strengthen the evidence for down regulation of apoptosis in pregnancy. Fas and p53 expression was supressed at all pregnancy time points measured and Casp6 was down regulated at both day 14 and day 18 of gestation. It was hypothesised that changes in expression may be regulated by changes to DNA methylation. Global methylation measurements and expression of DNA methylation associated enzymes (Dnmt1, 3a, 3b, Tet1, 2 and 3) initially suggested a decrease during pregnancy, supporting this hypothesis. However, methylated DNA immunoprecipitation sequencing showed that there were only 6 differentially methylated regions in the liver during pregnancy and only one of these corresponded to a change in gene expression. This suggests that DNA methylation was unlikely to be the mechanism responsible for the changes in gene expression observed. It was thought that the changes in the mouse liver during pregnancy might be brought about by exposure to pregnancy-associated hormones. To test this, mouse Hepa1-6 liver cells were exposed to a range of concentrations of oestrogen, mouse prolactin, human prolactin and human placental lactogen. No change was found in global DNA methylation and the expression of the Dnmt and Tet genes showed large variation. However, treatment with specific concentrations of the hormones reduced the variation seen in expression in these genes. As Dnmt expression has been shown to vary with the cell cycle, it was hypothesised that exposure of the cells to hormones at these concentrations led to an alignment of the cell cycle and, therefore, reduced the variation in expression. Flow cytometry was used to identify the proportion of cells at each stage of the cell cycle. It was found that treatment with human prolactinreduced the proportion of apoptotic cells and altered the distribution of cells at other points in the cell cycle. Having observed the response of the mouse liver to normal pregnancy, showing increased proliferation and decreased apoptosis, it was hypothesised that changing the maternal diet may disrupt this response. Female mice were fed increasing fat content diets (with reciprocal decrease in carbohydrate) and the expression of Ki67, cyclinB1, Fas, p53 and Casp6 measured. There were no significant changes in the expression of these genes. Phenotypic analysis of the mouse liver showed that both hypertrophy and hyperplasia play a role in the increase in size seen during pregnancy. Gene expression analysis added strength to this, as well as showing that a reduction of apoptosis provides an additional mechanism suggesting how this tissue growth is maintained. Use of an in vitro cell model showed that stimulation with prolactin may cause the decrease in apoptosis and at least contribute to the stimulation of cell proliferation. Together, these findings provide novel insights into the mechanisms that underlie the expansion of the mouse liver in pregnancy. The findings may also have implications in identifying targets for treatment in diseases such as hepatocellular carcinoma and obstetric cholestasis.

‘Inappropriate behaviour’ can be described as the thousand ‘slings and arrows’ that, on a daily basis, eat away at civility; such behaviours may be one-off events, or individual put-downs, that nevertheless cause the receiver significant harm. In this thesis, inappropriate behaviour is conceptualised as different from bullying, which involves the repetition of behaviours and is defined and supported within various legislation. Whilst there is research that focuses on the nature and impact of workplace bullying, there is very limited research that considers the impact that inappropriate behaviours can have on an individual. This interpretive phenomenological investigation, whereby Heidegger’s philosophical approach to phenomenology was used as a methodological framework support, explored the lived experiences of eight student midwives, who had experienced inappropriate behaviour within their academic and clinical environments. The research illustrates the nature of such experiences and further explores the resulting effects. The experiences disclosed by individual participants were initially identified as struggling, being out of sight out of mind and loss and bereavement. The main findings revealed three interpretative themes that described what inappropriate behaviour represented for the participants and how it impacted upon them. These were: ‘Breaching Covenant’, ‘Dispossession’ and ‘Liminality’. Each theme incorporated one super-ordinate theme, betrayal and struggling (Breaching Covenant), loss and bereavement (Dispossession) and finally angst and anonymity (Liminality). For the participants, inappropriate behaviour was seen as single acts most commonly perpetrated by clinical midwives, without a sense of malice or intention to cause harm. It is important that the difference between bullying and inappropriate behavioural acts become known by of all those involved with student midwives’ education and a concerted effort in changing attitudes is made to enable the development of both clinical and academic environments, where inappropriate behaviour is strongly contested and vigorously opposed.

Background: This research is about midwifery one-to-one support in labour. One-to-one support in labour is associated with improved birth outcomes. Uncertainty exists however as to what it is that produces such positive birth outcomes. UK publications advocate the midwife to provide one-to-one support in labour, but research findings question their ability to focus entirely on women due to their medical, technological and documentation responsibilities. All of these studies were based within hospital environments and none were completed in the UK. This indicates a gap in knowledge concerning how midwifery one-to-one support translates into practice in the UK and within midwife–led environments. Methods: The aim of this research was to explore midwifery one-to-one support in labour in a real world context of midwife-led care. An ethnographic approach was completed over three case study sites (Alongside midwife-led unit, freestanding midwife-led unit and women’s homes) each including ten labouring women receiving midwifery one-to-one support in labour. Findings: Two main themes: Balancing the needs of the woman and balancing the needs of the NHS organisation. Inside the birth environment midwives used their knowledge, experience, intuition and motivation to synchronise six components. These included presence, midwife-woman relationships, coping strategies, labour progress, birthing partners and midwifery support. Outside the birth environment midwives experienced surveillance and territorial behaviours which were heightened during transfer from a midwife-led birth environment to the labour ward. Conclusion: When a ratio of one midwife to one woman was achieved, midwives were 100% available for a woman in their care. This enabled midwives to be constantly present when required and provide total focus to tune into the needs of women and synchronise their care. Although midwives balanced the needs of the NHS organisation this did not impact on midwives capability to be present with women in labour.

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