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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
121

The importance of poly(A)-binding protein 4 (PABP4) in healthy pregnancy

Hrabálková, Lenka January 2016 (has links)
Healthy pregnancy requires a tightly regulated materno-fetal dialogue for processes such as embryo implantation, endometrial decidualisation (in the mouse), placentation and maternal adaptation to occur. Disruption of placental development as well as maternal adaptation can lead to fetal intrauterine growth restriction (IUGR) which increases the risk of late miscarriage/stillbirth (e.g. 53% of preterm stillbirth and 26% of term stillbirth are found to be IUGR). Furthermore, IUGR is a risk factor for neurodevelopmental conditions in childhood and for a spectrum of related adult health disorders such as cardiovascular disease and type II diabetes, often termed metabolic syndrome. Despite these pregnancy disorders being common (e.g. 1 in 200 pregnancies results in stillbirth in the UK) the molecular lesion(s) underlying their pathophysiology are poorly understood and in particular those with placental and/or maternal aetiologies most frequently remain unexplained. Here we investigate the hypothesis that poly(A)-binding protein 4 (PABP4) is required for healthy pregnancy in mice. PABP4 is an RNA-binding protein and a member of the PABP family which are central regulators of mRNA translation and stability. Using all four permutations of wild-type and knock-out crosses, we find that maternal PABP4-deficiency results in a reduced litter size and IUGR. The number of implantations at e8.5 were not reduced in Pabp4-/- females, implying that the reduced litter size was not a consequence of decreased ovulation, fertilisation or implantation frequency. Further longitudinal analysis (at e13.5, e15.5 and e18.5) reveals that fetal death primarily occurred between e18.5 and birth, suggesting these mice may provide a unique opportunity to inform on the maternal causes of stillbirth. The onset of IUGR, which was found to be symmetrical in nature, was established by e15.5 preceding the majority of fetal death. During pregnancy, a materno-fetal dialogue directs and responds to changes in gene expression to give rise to the placenta and adapt the maternal physiology. Defects in these processes may result in reduced growth and/or fetal death and were examined in Pabp4-/- mice to shed light on the mechanistic basis of these related phenotypes. Fetal to placental (F:P) weight ratio, whose changes can be indicative of placental insufficiency or placental adaptation in an attempt to aid fetal growth, was found to be increased in Pabp4-/- dams at e15.5 and e18.5 due to the presence of IUGR fetuses with placentas of normal weight. Consistent with this observation, placental volume was unchanged at e18.5. Total placental weight and volume alone fails to discriminate potential differences in the individual placental zones which include the labyrinth zone, where materno-fetal gas and nutrient exchange occur; the junctional zone, which has endocrine functions including those that promote maternal adaptation; and the decidua basalis, derived from the maternal endometrium and is the site of trophoblast invasion and maternal vascular remodelling in early pregnancy. Therefore, volumetric analysis of these zones and the maternal blood spaces, which transcend the decidua basalis and junctional zone, was undertaken. This showed no change in the maternal blood spaces or the labyrinth, the latter being the zone whose size is most frequently altered in IUGR. Critically however, the size of the maternally-derived decidua basalis was increased with a concurrent decrease in the size of the junctional zone. These morphological changes may play a causative role either through directly affecting placental function and/or by the reduced junctional zone failing to promote appropriate maternal adaptation. Alternatively, they may reflect compensatory adaptations to a primary defect elsewhere in the mother. Complementing these morphological studies, functional studies were undertaken: remodelling of maternal vasculature and the resistance index of vessels delivering blood to the fetus were assessed; as was delivery of nutrients to the fetus (measured by fetal glucose); and systemic maternal adaptations (maternal hormonal profile, circulating glucose levels and organ weights). Uterine, umbilical and decidual spiral arteries were examined, but displayed no apparent differences suggestive of normal blood supply to the fetus. However fetal blood glucose was reduced suggesting a reduced delivery of nutrients important for fetal growth. This was not due to lower circulating maternal blood glucose levels, and mRNA levels of the placental glucose transporters Glut-1 and Glut-3 were not reduced but upregulated, suggestive of an attempt to compensate for reduced fetal glucose. Furthermore, upregulation of at least one system A amino acid transporter mRNA, Snat-2, was observed. The maternal physiological state of PABP4-deficient dams showed deviations in some organ weights (e.g. spleen weight is reduced at e13.5 and e15.5) and the levels of some circulating hormones (e.g. estradiol is deceased whereas progesterone is increased at e18.5). However, future work will be required to determine which, if any, of these changes are primary defects rather than downstream consequences and to identify which mis-regulated mRNAs/pathways within in the materno-fetal dialogue underlie the phenotype. Taken together, my results suggest that the regulation of mRNA translation/stability by PABP4 is critical to achieving the correct pattern of gene expression within the materno-fetal dialogue to enable appropriate placentation and maternal adaptation. Furthermore, my results suggest that Pabp4-/- mice provide a unique opportunity to further understand the maternal causes of a spectrum of related pregnancy complications including IUGR, late miscarriage and stillbirth.
122

The utilization of the partograph by midwives in Lebowakgomo and Zebediela level 1 hospitals in the Capricorn District of the Limpopo Province, South Africa

Shokane, Morogwana Anna January 2011 (has links)
Thesis (M.Cur.) --University of Limpopo, 2011 / Introduction and aim: Globally it is of paramount importance that all pregnant women in labour are monitored by midwives utilizing a partograph so that a live baby is delivered. Midwives seemed not to utilize the partograph correctly when monitoring women in labour. The purpose of this study was to determine the utilization of the partograph by midwives in the labour wards of Lebowakgomo and Zebediela level 1 hospitals in the Capricorn District of the Limpopo Province, South Africa. The research question was, “What skills and knowledge do midwives have on the utilization of the partograph for monitoring pregnant women in labour”. The objectives of this study were to explore and describe the utilization of the partograph by midwives in Lebowakgomo and Zebediela level 1 hospitals in the Capricorn District of the Limpopo Province, and to develop guidelines that would assist midwives to effectively utilize the partograph hence provision of quality midwifery care. Research Design and method: The research design was qualitative, descriptive, explorative and contextual in nature. The population comprised all midwives registered with the South African Nursing Council and practicing as such in Lebowakgomo and Zebediela level 1 hospitals. A purposive sampling technique was used to select 15 participants. Data were collected using semi-structured in–depth interviews with a guide. The semi-structured in-depth interviews were conducted until data were saturated. Trustworthiness was ensured by credibility, dependability, transferability and confirmability. Ethical clearance to conduct the study was obtained from the University of Limpopo and from the Department Health and Social Development. The principles of informed consent, confidentiality and anonymity were observed during the study. Data were analyzed using the Tesch’s approach as described by Creswell (1994) cited in de Vos (2005:333). Conclusions: The following themes emerged during data analysis: monitoring of foetal status during intrapartum, monitoring of the progress of labour during intrapartum, monitoring of the maternal status during intrapartum, and shortage of staff in the labour wards. Guidelines which aimed at improving midwifery care were formulated.
123

Clinical leadership on the labour ward

Parkin, Julie January 2016 (has links)
Introduction: Clinical Leadership is a way of facilitating change and increasing the quality of care at the front line of practice. However, the failure of midwifery leadership and being designated an oppressed group questions the ability of midwives to practice as clinical leaders in the labour ward environment. Whilst there is some research relating to clinical leadership in nursing, no research exists that investigates the clinical leadership of midwives who are directly involved in giving care to women. Aim: The aim of this research was to explore clinical leadership on the labour ward and to develop an understanding of the associated characteristics of clinical leadership. The attributes that delineated effective clinical leadership were examined in addition to associated professional discourses and relationships of power that existed on the labour ward. Methods: A critical ethnographic approach was undertaken on the labour ward of a district general hospital and a teaching hospital in the North of England, using participant observation and semi-structured interviews. A total of sixty-nine hours of participant observation was undertaken. A purposive sample of 30 midwives were interviewed in the first instance and further interviews were undertaken with 18 midwives who were nominated as effective clinical leaders by the midwives in the initial interviews. Data were examined through the lens of Bourdieu’s Theory of Practice. Findings: Clinical leadership existed at different levels on the labour ward, however, midwives mostly identified LWCs in this role. LWCs’ clinical leadership was necessary, contradictory, gendered, socialised and unsupported within the hierarchical, high-risk and fearful labour ward. A combination of heroic and values-based clinical leadership was required to maintain safety and facilitate productivity. Heroic leadership, the high level of accountability and symbolic capital invested in the LWC led to a loss of autonomy for other midwives, a lack of dissent and difficulty initiating changes in practice. The contradictory nature of the LWCs’ work and a lack of support led to them experiencing both emotional and physical stress. Within an increasingly highrisk labour ward environment the LWC clinical leaders experienced professional misrecognition and discrimination that resulted in dysfunctional inter-professional relationships and keeping the obstetricians away from women. Conclusion: A high level of responsibility invested in the LWC combined with socialisation led to heroic leadership which fostered dependency prevented change and innovation. Inequalities of power and dysfunctional relationships were symptoms of a system failure that does not support midwifery practice or woman-centred care. Recommendations are made for policy, education, practice and future research.
124

Women's decisions to exercise in pregnancy : negotiating conflicting identities

Hassall, Jenny Louise January 2016 (has links)
Substantial benefits can be gained by participating in regular physical exercise, however only a minority of women meet current pregnancy exercise recommendations and there is limited understanding of women’s decision-making regarding exercise in pregnancy. The purpose of this constructivist grounded theory study was to develop a theoretical insight into the factors that influence women’s decisions regarding exercise in pregnancy and how they process the influences and multiple alternatives they encounter. The constructivist approach drew on the subjective researcher/participant interrelationship to co-construct meaning from the data and ultimately render the women’s experiences into theoretical interpretations. The theory presented was built inductively from the experiences of 10 pregnant women who exercised regularly, supplemented by insights from theoretical sampling of fitness experts, internet forums and extant literature. Longitudinal, audio-recorded semi-structured interviews occurred twice during each pregnancy and 6-8 weeks postnatal. Data generation and data analysis ran concurrently and iteratively using the constant comparative method of analysis. Theoretical constructs generated by the data were progressively amplified and clarified through a series of inductive-deductive cycles and theoretical sampling that drove the evolving interview schedules. Theorising ideas in the form of detailed memos was a fundamental part of the analysis and enabled a detailed audit trail to be established. The resultant substantive theory of ‘Accommodating the pregnant self’ conceptualises pregnancy as a transitional period during which women’s self-identity is modified. ‘The exercising self’ was a salient and valued facet of the women’s self-identity and continuing to exercise enabled women to maintain a degree of continuity and control that was integral to their sense of maintaining and to a degree regaining their past valued self. Decisions regarding exercise were influenced by a complex interplay of contextual factors that simultaneously encouraged exercise and rest. This consequently triggered a degree of identity conflict between two domains of their self-identity, ‘the exercising self’ and ‘the pregnant self’. The women reacted to the challenges to their identity through the process of self-identity regulation. Through this process they gradually re-constructed their self-identity to accommodate their pregnant self while contemplating possible future selves against various self and social normative standards. Negotiating conflicting identities was an integral component of the decision-making process, and ultimately resulted in many of the women modifying their activities to accommodate the pressures they faced to conform to social ideologies of ‘the pregnant self’. The theory explores a range of strategies that the women used to deal with identity conflict, particularly drawing on selective perception and self-justification to resolve cognitive dissonance. It also highlights a duality in the factors that influenced their decisions which suggests women’s identity characteristics resulted in a propensity for behaviour to be steered by either internal (personal) or external (relational and environmental) influences. The substantive theory underscores the significance of self-identity in steering the decisionmaking process. The findings provide insight into how women might be better supported to make informed and assured decisions regarding lifestyle choices. The theoretical potential to inform interventions to enhance activity levels in a wider population is highlighted.
125

Maternal self-efficacy in mothers of children with and without clinical feeding problems

Jordan, Caroline January 2016 (has links)
The understanding of maternal factors associated with child feeding problems is limited due to a lack of research which has examined a comprehensive range of maternal factors and the existing literature focussing on a narrow range of ideas about the wider familial context in which feeding problems occur. The broad aim of this thesis is to investigate maternal parenting of children with and without clinical feeding problems to provide insights into the wider context in which feeding problems occur. In study 1, thematic analysis of interviews with 10 mothers of children with, and 10 mothers of children without, clinical feeding problems revealed that mothers of children with clinical feeding problems appeared to have less maternal self-efficacy for managing parenting challenges than mothers in the non-clinical group. A template analysis found that these perceptions seemed to be informed by four theoretical sources of self-efficacy: mastery experiences, verbal persuasion, vicarious experience and physiological state. In study 2, 278 mothers of children with and without clinical feeding problems completed existing self-report measures of maternal self-efficacy. It was found that lower levels of maternal self-efficacy for establishing structure and routine around instrumental child care tasks and for implementing discipline and setting limits for the child was predictive of problematic child feeding behaviour and maladaptive maternal responses to child feeding problems. In study 3, 215 mothers of children with and without feeding problems completed self-report measures of the theoretical components of self-efficacy (mastery experiences, verbal persuasion, vicarious experience, physiological state). Physiological state was found to be the strongest predictor of maternal self-efficacy for establishing structure and routines as well as for providing discipline and setting limits for the child. Maternal self-efficacy mediated the relationship between physiological state and problematic child feeding behaviour and the relationship between parenting stress and maladaptive maternal responses. The final study was a pilot study using autophotography. This study explored parenting dimensions and tasks which contributed towards perceptions of maternal self-efficacy in 13 mothers of children without clinical feeding problems. Findings suggested that child feeding was an especially difficult and complex task for mothers to manage, with many mothers reporting perceptions of low efficacy for managing mealtimes. This appeared to be due to the large number of health related concerns and the worry mothers felt when children did not eat a healthful diet. Overall, results of this thesis suggest that mothers who lack confidence in their ability to manage child behaviour report more problematic child feeding behaviours and use more maladaptive strategies for managing feeding problems. Findings of the studies in this thesis suggest that mothers of children with feeding problems, and who are experiencing high levels of stress, may be especially vulnerable to lower levels of maternal self-efficacy which may exacerbate difficulties. Increasing maternal self-efficacy for providing structure, routines and discipline in mothers experiencing feeding problems in their children may improve outcomes for those affected.
126

Predicting and understanding physical activity behaviour during pregnancy : a multiphase investigation

De Vivo, Marlize January 2017 (has links)
Background: The benefits of physical activity during pregnancy extend to both mother and baby, however, little is known about the reasoning behind expecting mothers' decision to initiate or maintain regular participation during this period. Objective: The main purpose of this research project was to investigate the socio-cognitive determinants of pregnant women's physical activity behaviour. Method: A mixed methods research approach using a multiphase design with the Theory of Planned Behaviour (TPB) as conceptual framework guided the investigation. Application of the TPB required both qualitative (Study One; n = 18) and quantitative (Study Two; n = 78) cross-sectional data to be collected which addressed the aims of understanding and predicting physical activity behaviour during pregnancy. A further qualitative study (Study Three; n = 10) involving semi-structured interviews with community midwives augmented the investigation. Results: Whilst findings from individual studies have merit, a major strength of this study pertain to the 'meta-inferences' drawn from the combination of studies. Specifically, findings suggest that (1) pregnant women do not have access to the necessary information that would allow them to make informed decisions regarding their engagement in physical activities; (2) a co-ordinated effort is required to support pregnant women in overcoming barriers associated with regular exercise participation; and (3) profiling pregnant women according to motivation and behaviour status could serve as a useful and manageable starting point for intervening to produce positive changes in pregnant women's physical activity behaviour. Conclusion: In achieving better health and ensuring greater health outcomes for mothers and babies it is necessary to consider the factors involved in behaviour change, identify opportune moments to intervene, and involve health professionals in facilitating and supporting the lifestyle changes that may be required.
127

An analysis of the meaning of confidence in midwives undertaking intrapartum care

Bedwell, Carol January 2012 (has links)
Midwives are often the lead providers of maternity care for women. To provide the variety of care required by women, they need to be confident in their role and practice. To date, only limited evidence exists in relation to confidence as experienced by midwives. This thesis aims to explore the phenomena of confidence through the lived experience of midwives. In particular, this will encompass confidence in the context of the intrapartum care setting. The theoretical basis for the study was hermeneutic phenomenology, guided by the work of Heidegger and Gadamer. Midwives were recruited from three clinical settings to obtain a diversity of views and experiences. Rich data from diaries and in-depth interviews, from twelve participants, provided insight into the phenomena of confidence and the factors midwives encountered that affected their confidence. The phenomena of confidence consisted of a dynamic balance, between the cognitive and affective elements of knowledge, experience and emotion. This balance was fragile and easily lost, leading to a loss of confidence. Confidence was viewed as vital to midwifery practice by the participants of the study; however, maintaining their confidence was often likened to a battle. A number of cultural and contextual factors were identified as affecting confidence within the working environment, including trust, collegial relationships and organisational influences. Midwives also described various coping strategies they utilised to maintain their confidence in the workplace environment. This study provides unique insight into the phenomena of confidence for midwives working in intrapartum care, resulting in a number of recommendations. These highlight the importance of leadership, education and support for midwives in the clinical environment in enabling them to develop and maintain confidence in practice.
128

Assessment of risk of drug exposure in early pregnancy in women in a rural community in Malawi

Kabuluzi, Ezereth January 2012 (has links)
Introduction: Medication use by women of childbearing age is common. During pregnancy, medications should be used cautiously because some are teratogenic and/or feto-toxic, especially during the first trimester. Few studies have assessed exposure to contraindicated medications in developing countries. Aims and objectives: The overall aim was to assess the risk of exposure to contra-indicated medicines in early pregnancy (less than 13 weeks gestation) in Malawi. Specific objectives were to (i) determine the proportion of women inadvertently prescribed contraindicated medicines in the first trimester of pregnancy in a general outpatient clinic; (ii) explore women's beliefs, views and practices concerning medication use during pregnancy; (iii) determine the prevalence of congenital abnormalities by review of records at community and central hospital sites; (iv) to make appropriate recommendations for policy and practice in Malawi relating to medication use in pregnancy. Methods: A mixed methods approach was used. Survey data were collected at an outpatient clinic at Mitundu Community Hospital (MCH) between 1st February 2010 and 30th July 2010 to determine the range of medicines taken by potentially pregnant women. A pregnancy test established the pregnancy rate in this group. These data were summarised using descriptive and inferential statistics, and the proportions of exposed women who were pregnant were estimated. To understand women's beliefs, views and practices, semi-structured interviews were held with 21 pregnant women at their first visit to an antenatal clinic at MCH. The main themes were identified by Framework analysis. Retrospective data were abstracted from birth registers at MCH and Kamuzu Central Hospital (KCH) to estimate the prevalence of congenital abnormalities. Results: Of 1103 women prescribed contraindicated medicines in the outpatient clinic, 272 were potentially pregnant. Of the 63 (23.2%) confirmed pregnant (95% CI 18.3%-28.6%), 20 knew or thought they were pregnant, 22 were not sure and 21 did not think they were pregnant. Only 153 (55.9%) were asked about pregnancy by a medical officer before prescription. 3.2% of all pregnant women (95% CI 2.5%-4.1%) attending the clinic were estimated to have been prescribed contraindicated medicines. Eight pregnant women also self-prescribed unsuitable modern medications. Women accepted as safe any medications prescribed in the clinic. They also accepted potions given by traditional birth attendants to counter witchcraft, which they believed caused pregnancy loss. They did not associate use of these medicines with congenital abnormalities, the prevalence of which (6.58/1000 births at MCH, 14.55/1000 births at KCH) was similar to international figures. Conclusion: The study highlights areas of concern for practice, policy and research relevant to maternal health care in Malawi. Clinicians need to reduce the rate of exposure to potentially harmful medicines by paying attention to the possibility of pregnancy in women of childbearing age. There is also a need to facilitate public awareness especially among women about dangers of taking medicines.
129

Testing HIV positive in pregnancy : a study of women's experience and personal testimony following a positive human immunodeficiency virus (HIV) antibody test result during pregnancy

Lingen-Stallard, Andrew January 2013 (has links)
Midwives recommend antenatal HIV testing in pregnancy for all women. However,limited information is available on the experience of testing HIV positive in pregnancy.This thesis explored women’s experiences of receiving a positive HIV test resultfollowing antenatal screening in United Kingdom (UK). Black Africa women have highlevels of HIV infection in the UK and notably all participants were African in origin.The theoretical basis for the study was hermeneutic phenomenology, proposed byHeidegger (1962) and further guided by van Manen (1990), exploring essence andmeaning of this lived experience. Thirteen women were recruited and participated in asemi-structured interview. Participants were recruited from two NHS sites, several HIVsupport organisations and a national advert, in order to obtain diversity of this livedexperience.The emergent phenomenon is transition and transformation of “being,” as womenintegrated HIV into their lives. As women transformed with the HIV diagnosis theybalanced major themes. The major themes consisted of shock and disbelief; anger andturmoil; loss of old self; stigma and confidentiality issues and acceptance and resilience.Primary and secondary themes included: extreme reaction on being given a diagnosiswith a cultural belief that they would die; disbelief as the result was unexpected;sadness and loss of their old self; turmoil wanting to terminate the pregnancy; isolationfrom significant others; breakdown of their relationship and considering suicide and selfharm. Most reported the pervasiveness of stigma, and how they managed both thisstigma and HIV in their lives; growing resilience was apparent with time. Copingstrategies included keeping HIV “secret” and their child or children becoming the primefocus of life, with less importance on self.This study gives midwives a unique understanding of the complexities for womentesting HIV positive and supports Bonanno (2009) and Kübler Ross’ (1969 & 2005)findings on personal loss. Additionally this study provides a unique insight into thephenomenon of transition and transformation for women who tested positive inpregnancy and explores the factors and impact of testing HIV positive. The impact of anHIV diagnosis is culturally difficult for African women and had major implications andchallenges for their future life. Midwives are crucial in supporting and improving theexperience of women when they test HIV positive.
130

Parturition, oxytocin, inflammation, myocyte damage and obesity : a study of myometrium and haematological parameters in human pregnancy and labour at term

Higgins, Claire Angela January 2013 (has links)
The process of parturition resulting in the delivery of a newborn is a fundamental event ensuring survival of the species. In humans, the main clinical problems of parturition include activation of the process too early or too late resulting in the delivery of pre-term and post-term infants, both with their own implications for future health for the mother and baby. Additionally, where parturition systems are not activated correctly, dysfunctional labour with the resulting need for caesarean delivery (CS), in addition to atonic post-partum haemorrhage can also ensue. Overall, in the UK up to 40% of pregnancies are affected by one of these problems. However, the exact processes involved in the initiation and maintenance of parturition in the human are not fully understood. With such an important event, influences are most likely to be multi-factorial, with hormonal, mechanical, inflammatory, biochemical and maternal environmental factors playing a part. The aims of this thesis were to investigate influences on parturition in human pregnancy. Firstly, the myometrial transcriptional effects of long term exposure to the uterotonic oxytocin (OT) were examined. Further investigation of the myometrial and maternal peripheral response to uterine contractions in-vitro and in-vivo was also made with particular reference to the role of inflammation and myocyte damage. Additionally, the influence of maternal factors, particularly obesity, on the myometrial in-vitro contractile function and response to OT was studied. Initially, 150 gene arrays were produced using the Illumina platform. The samples were derived from myometrium taken at pre-labour CS which subsequently underwent functional contractility experiments in an organ bath. Five drug environments were studied, namely OT, acetic acid (OT vehicle), ML7(a tocolytic acting via inhibition of myosin light chain kinase), ML7 & OT and finally DMSO (ML7 vehicle). Additionally, five time-points of 0, 1, 2, 4, and 6 hours after drug addition were used, resulting in 5 samples for each drug and time combination. The results indicated that despite a clear enhancement of myometrial contractile activity by OT, this functional response does not appear to be mediated by cellular transcription. However, there was a clear contraction and time dependent transcriptional wave, with overrepresentation of genes associated with inflammation and cellular damage/apoptosis, and down-regulation of pathways concerning cellular metabolism. These findings were confirmed by QPCR on further myometrial samples undergoing additional in-vitro functional studies. In addition to the temporal and contractile association with the inflammatory response, our data suggest inflammation occurs in response to myocyte cellular damage regardless of mode of damage e.g. contractile or chemically induced. This was demonstrated by inflammatory upregulation in myometrium exposed to the tocolytic agents nifedipine and ritodrine, which is not seen in response to ML7. Additionally, the myometrial inflammatory response was enhanced by the infective agent LPS. However, contrary to other proposals, the enhanced inflammatory response of the myometrium did not alter or promote the in-vitro contractile ability of the myometrium or its response to OT. This myometrial transcriptional data therefore suggests that the inflammatory response of labour is associated with contraction, chemical or infection induced myometrial cellular damage, but would not be considered necessary for a contractile response. Our in-vivo study of peripheral changes in the maternal circulation again supported our in-vitro myometrial data. Data showed that the effect of pregnancy at term was limited to increased white cell count driven by a neutrophilia, with no suggestion of leukocyte priming prior to labour. Additionally, term pregnancy is associated with an increase in CRP, an increase in GCSF (corresponding with the neutrophilia) in addition to suppression of the chemokines CCL11 and CCL22. Subsequently, we found that repeated blood samples taken at 2 hourly intervals during term labour induced dramatic changes in inflammatory cells and inflammatory mediators in the maternal circulation. Importantly, these changes occur in a co-ordinated time and contraction dependent manner, with the degree of inflammation associated with the length of time in labour and the degree of myocyte damage as measured by circulating CK and Mb. Our study of the influence of maternal factors on myometrial contractile ability and response to OT examined in-vitro myometrial contractility of 609 myometrial strips from 85 women. We demonstrated that maternal obesity does not impair spontaneous or OT induced myometrial contractions in-vitro. Furthermore, maternal age, ethnicity, parity, previous caesarean delivery,gestation at delivery and birthweight do not influence in-vitro myometrial spontaneous or OT induced contractile activity. This therefore suggests that the observed implication of these maternal and infant factors on parturition in-vivo (high rates of induction of labour, high rates of intrapartum caesarean delivery and post partum haemorrhage) cannot be explained by an effect on myometrial contraction per se. This therefore merits further investigation as to alternative mechanisms to ultimately promote and effective, uncomplicated and safe labour and vaginal delivery for at risk mothers. In summary, this thesis provides evidence that the myometrial contractions of human labour, whether spontaneous or OT induced are capable of inducing a temporal wave of transcriptional changes associated with the processes of inflammation, cellular damage/apoptosis with inhibition of cellular metabolic processes. In addition, maternal peripheral circulating factors mirror the myometrial transcriptional changes. These changes are highly comparable with those seen in response to exercising skeletal muscle, and in this model have been shown to play an important role in muscle repair and remodelling after exercise. Therefore, we would suggest that the inflammatory reaction typically associated with human labour occurs as a non-specific response to contraction induced cellular damage and may play a role in postpartum repair and remodelling of the uterus.

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