Previous studies have associated intracellular calcium ([Ca2+]i) oscillations in vascular smooth muscle cells (SMC) with vasomotion in multiple species. In normal and pre-eclamptic pregnancies, there is strong evidence to suggest that the intrauterine environment is hypoxic. The aim of this study was to investigate whether ATP and [Ca2+]i oscillations play a role in modulating vasomotion during hypoxia in human umbilical blood vessels. The results obtained from in vitro studies using firefly luciferase assay and quinacrine staining indicated that human umbilical artery and vein endothelial cell (HUAEC, HUVEC respectively) constitutively released ATP and, in HUVEC at least, the release was accentuated by hypoxia (7.6 mmHg O2, 30 min). This release is dependent on the PI3K/ROCK pathway, and on normal vesicular transport. Further, application of ATP to human umbilical artery SMC induced dose-dependent [Ca2+]i oscillations, which was mediated by P2Y4 receptor. Moreover, ex vivo data from freshly isolated umbilical artery rings showed that acute hypoxia increased the frequency of vasomotion. It is therefore proposed that the findings of the present study is important in the understanding of the behaviour of human umbilical vessels in normal pregnancy, but may also have implications in the pathophysiology of complicated pregnancy such as pre-eclampsia.

Advances in technology have led to the miniaturisation of hysteroscopes without compromising optical performance. This development has facilitated the routine use of diagnostic hysteroscopy in an outpatient setting without the need for general anaesthesia. Further developments have expanded hysteroscopy from a simply diagnostic intervention to an operative one with a plethora of hysteroscopic surgical procedures. The work in this thesis has adopted a mixed methodological approach to rigorously evaluate patient selection, feasibility and efficacy of office hysteroscopy. Based on the results of this thesis we recommend: 1) Women with recurrent PMB should be investigated with either hysteroscopy or saline infusion sonography. 2) Vaginoscopy should probably be used in preference to other techniques to introduce the hysteroscope into the uterine cavity. 3) Women who have a uterine cavity >9cm or dysmenorrhoea should be warned they are more likely to require further intervention after endometrial ablation. 4) There appears to be no difference between the effectiveness of bipolar radiofrequency ablation and thermal balloon ablation at five years of follow up. 5) Women who present with abnormal uterine bleeding and an endometrial polyp should have it removed. 6) The hysteroscopic morcellator should be used in preference to bipolar resection for endometrial polyp removal.

Pre-eclampsia is a pregnancy-specific, multi-system disorder of placental origin. Affecting between 2-8% of women, it is one of the leading causes of both maternal and fetal morbidity and mortality in the United Kingdom. Although the disorder presents after 20 weeks gestation with the classic symptoms of hypertension and proteinuria, the pathological process(es) leading to this syndrome initiate early in the first trimester. In current clinical practice, prediction of those who will get the disease and those who will have a poor outcome once it develops is poor. This thesis focuses on novel ways to enhance the prediction of the development of pre-eclampsia and poor outcome once the syndrome manifests. Firstly, the current risk factors for pre-eclampsia were challenged. Racial variation in these risk factors has demonstrated the importance of considering maternal ethnicity when assessing the likelihood of developing the disease. Obese Black women were more likely to develop pre-eclampsia than obese white women (aOR 2.06 (95%CI 1.34-3.23) p=0.002). In the normal BMI group Black women were less likely to develop pre-eclampsia than White women (aOR 0.421 (95%CI 0.24-0.73) p<0.001). Younger (<20 years of age) Black women were less likely to develop pre-eclampsia than younger white women (aOR 0.628 (95%CI 0.49-0.83) p<0.001). Conversely, older (>35 years of age) Black women were more likely to develop pre-eclampsia than older White women (aOR 1.67 (95%CI 1.39-1.99) p<0.001). Secondly, first trimester maternal plasma studies have identified a cohort of potential disease (and pathophysiological) markers that may allow for the development of an early screening test for pre-eclampsia. The ratio of angiotensinogen to Kallikrein is raised in the first trimester of pregnancies that later develop pre-eclampsia (p<0.001). The receiver operator curve (ROC) for the ratio of angiotensinogen to kallikrein had an area under the curve (AUC) of 0.81 (SE=0.05). A cut-off value of >0.27 has a sensitivity of 0.9 (95% CI = 0.74 – 0.97), a specificity of 0.5 (95% CI = 0.24-0.65), positive predictive value (PPV) 0.63 (95%CI = 0.47-0.75) and negative predictive value (NPV) of 0.87 (95% CI = 0.53-0.96) in predicting the onset of preeclampsia. Common haematological and biochemical tests are presented as markers for both the development of the disease and poor outcome when it occurs. The ratio of Neutrophil to Lymphocyte (NLR) is raised in the first trimester of pregnancies that develop pre-eclampsia (p<0.001). The ROC of the ratio to Neutrophil to Lymphocyte has an AUC of 0.84 (95% CI = 0.85-0.95). A cut off value of 2.53 has a sensitivity of 0.92 (95%CI = 0.85-0.95), specificity of 0.6 (95%CI = 0.51-0.67), PPV 0.68 (95%CI = 0.6-0.74) NPV 0.87 (95%CI = 0.8-0.93) for predicting the onset of pre-eclampsia. At the time of diagnosis of pre-eclampsia, a raised NLR predicts poor maternal outcome and the need for a caesarean section due to fetal distress (p<0.05). In addition, a reduced level of bilirubin predicts both poor fetal and maternal outcome and the need for a caesarean section (p<0.05).

Maternal obesity increases the risk of numerous maternal and fetal complications of pregnancy. Women were recruited at booking for antenatal care. Each subject was examined in the first, Second and third trimester of pregnancy as well as twelve weeks post partum. Using non invasive techniques microvasular function was measured at each visit. Fasting bloods were taken. This assessment allowed us to observe microvascular function, inflammatory response, dislipidaemia and changes in fatty acid composition with advancing gestation and the degree of recovery in the post partum. By recruitment of women with varying body mass index (BMI) values we were able to examine the influence of maternal BMI on these responses to pregnancy.

This thesis examines the function of discursive paradigms in the process of subjectivisation and the formulation of objects in the development of the human sciences. The history of childbirth practices exemplifies the operations of paradox and paradigm, and of epistemic changes and continuities, in relation to medical, ethical, and pedagogic discourses. The recent past has brought rapid change in the practices and outcomes of parturition with regard to technologisation, and the improvement in mortality rates. The achievement of technological childbirth has a complex and paradoxical history, and should be understood other than as an inevitable and progressive phenomenon of scientific endeavour, or as a conspiracy of patriarchy which victimises and subjugates women as a matter of intentionality. The histories of the parturient and of the midwife are only partially linked. An examination of childbirth history reveals some of the implications of phallogocentricity for the history of women and for the constitution of gender and gender relations. Midwifery has its own unique but unmistakeable place in the historical discourse of pathologisation and professionalisation - and cannot be regarded simply as an arena of masculine appropriation. The mechanisms for change in parturial practices have been developing to facilitate the modifications of recent history since around 1800, but there are discursive resonances which are linked also to changes in pedagogic organisation which began in the Middle Ages. Further, in order to analyse and evaluate the history of parturition over the past two hundred years, it is necessary to examine the paradigmatic structures based upon dialectical reasoning which have dominated the development of the human sciences since antiquity. Childbirth provides examples of many historical exigencies which informed a panoply of disparate effects, but it is also in many respects unique and anomalous. An exploration of the operations of power, knowledge and influence in this sphere, reveals as much in terms of its resistances as its susceptibilities, to medical appropriation. The history of childbirth is unusual insofar as the technologies and innovations that developed in relation to it, were in fact, slow to be implemented. Evidence of such paradigmatic dysjunction is provided by the examples of the use of forceps, asepsis and anaesthesia in the nineteenth century. This thesis addresses aspects and effects of professionalisation, and the increasingly disciplinary implications of expert discourses for the pregnant and parturient woman in the twentieth century.

"I know that every day I am gaining experience ... learning more" (Int. 6(a)) This thesis examines the social practices and associated learning that shape the meaning of midwifery for new members of the profession. In doing so it explores the extent to which the implications of practice either liberate or circumscribe midwives' identity formation. The thesis further suggests how this identity formation may impact upon commitment to a long term career in midwifery. The theoretical framework for this thesis acknowledges that continuing professional development and evidence of recognised learning activity is, for all midwives, a professional requirement. However, less attention has historically been paid to the unstructured, unintended and relatively informal learning that occurs within and throughout midwives' involvement in everyday practice. It is through these forms of learning, and drawing upon data elicited through surveys, interviews and diaries, that this thesis seeks to make a contribution. Using a social model of learning, particularly through Wenger's (1998) work on communities of practice, the development of identity is presented as a negotiated process mediated to a greater or lesser degree by workplace relationships. Whilst relationships with pregnant women form an important element of this process, the thesis argues that collegial relationships generally assume greater importance and impact on the development of identity and meaning for newly qualified midwives. By situating the everyday experiences of newly qualified midwives within a broader theoretical debate about social learning, identity and the making of meaning, this thesis suggests that the contemporary 'doing' of hospital based midwifery remains within what are fairly narrowly prescribed, contested, yet firm boundaries. The development, existence and negotiation of these boundaries is central to the space which pregnant women, midwifery and midwives can occupy. These boundaries are simultaneously hierarchical, intra professional and personal. Furthermore, in practice, these boundaries are frequently unclear and rapidly changing. Whilst this contributes to a potentially dynamic opportunity for identity formation, the thesis demonstrates how this also transpires to contribute to an unstable, frustrating and frequently challenging context particularly for newly qualified members of the profession. Overall, this thesis contributes to an understanding of the development, or lack of development, of midwifery practice at theoretical, conceptual and practical levels. Viewing practice as social learning offers a new perspective on the opportunities and challenges inherent in the current model of care. Simultaneously it suggests a new perspective on the recruitment crisis faced by the profession and accordingly the opportunity for new potential solutions.

The aim of this study was to assess risk factors to PTSD following childbirth incorporating a longitudinal design. Since the introduction of DSM-IV (APA, 1994) there has been an awareness in the literature that women can develop PTSD following childbirth. The first study in this thesis provides a comprehensive review of the literature in this area and the clinical implications of the disorder. The aim of the second study was to investigate the factor structure of a questionnaire measure (PLDQ) that has been used in past studies to assess women's perceptions of labour and delivery. The findings from this study indicate that the PLDQ consists of three internally reliable factors that can assess a woman's perception of pain, staff support/care and fear during labour and delivery. The scale can differentiate among women on these factors according to type of delivery. The aim of the third paper was to assess risk. factors to PTSD across time in the antenatal period, appraisal factors during delivery with the PLDQ, and maintenance factors in the postnatal period. There is an absence of studies in the literature that assess risk factors to PTSD over time. The results of this study indicate that postnatal depression (PND) and a negative appraisal of staff support and care during labour and delivery can predispose women to PTSD at 5-8 weeks following delivery. At 10 -14 weeks the relationship between PTSD and PND was still consistent. The clinical implications of the research are discussed for screening women at risk of PTSD following childbirth, assessment of a woman's appraisal of a difficult labour and delivery and the provision of support in the postnatal period.

No description available.

Background: GDM is a state of glucose intolerance first diagnosed in pregnancy. It is a pre-diabetes state, predisposing both the mother and offspring to future risk of diabetes. GDM is associated with increased risk to macrosomia, adiposity, Caesarean Section (CS) delivery, shoulder dystocia, and neonatal hypoglycaemia. SA have a greater than two fold risk of both GDM and future diabetes risk compared to WC. However, despite having higher levels of hyperglycaemia in pregnancy, SA babies are amongst the smallest babies in the world. The mechanism behind this increased glycaemic risk in SA is complex, multifactorial and unclear. Disordered hypothalamic-pituitary-adrenal axis (HPA) has been linked to adult diabetes, obesity and metabolic syndrome in WC but has not been studied in SA. The current management of GDM is largely based on evidence from studies in WC and has been extrapolated to other ethnic groups such as SA. This includes: diagnostic criteria to define GDM, postnatal screening methods for postpartum glucose abnormalities, effect of GDM on offspring birth weight (BW) and fetal growth in GDM. Through this research we aim to explore the ethnic differences between SA and WC in the applicability of diagnostic criteria, post partum screening methods, effect of GDM on BW, fetal growth patterns in GDM and also examine ethnic differences in HPA activity as a potential mechanism underlying the increased glycaemic risk in SA in pregnancy. Methods: i. Retrospective analysis of a routinely collected multicentre data (n=14477) over a 3-year period was used to study the applicability of various GDM diagnostic criteria and post partum screening methods. A subgroup analysis of the above data set was used to compare fetal growth between SA and WC (177 WC and 160 SA). ii. A retrospective analysis of a large birth weight cohort (n=53,128) from Leicestershire between 1994 and 2006 was used to compare the effect of maternal diabetes and GDM on BW in SA and WC. iii. To examine fetal growth in SA, a retrospective case control analysis of serial fetal biometry was performed between GDM and control population from India. (178 controls and 153 GDM) iv. To explore underlying HPA dysfunction as a potential mechanism for increased glycemia in SA and ethnic differences in HPA behaviour a prospective cohort study comprising of high risk pregnant SA and WC women was performed. Diurnal salivary and urinary cortisol excretion was studied in relation to glycaemia in SA and WC (n=100, 50 SA, 50WC) Results: i. The newer IADPSG detects obese women with mild fasting hyperglycaemia. The benefits of treatment of hyperglycemia are not well established. The increase in detection rates of GDM with the new NICE and IADPSG criteria were uniform across ethnic groups in a selectively screened population. ii. Postnatal screening with oral glucose tolerance test (OGTT) is associated with poor uptake in all ethnic groups, which improves substantially with using HbA1c. SA were more likely to attend postnatal screening with HbA1c compared to WC. Screening for postnatal diabetes using FPG is more likely to miss women of non-WC ethnicity owing to the larger proportion of post-load glucose abnormalities. iii. The BW increase associated with maternal diabetes was lower in SA by 139g compared to WC. iv. Important ethnic differences in fetal growth were noted. SA fetuses had overall smaller measures of head and abdomen circumferences, but with disproportionately smaller abdominal circumference compared to WC, signifying early evidence of a head sparing growth restricted pattern. v. SA fetuses of GDM mothers showed early evidence of increased abdominal adiposity at 20 weeks with smaller measures of other fat free mass and skeletal growth compared to non-GDM controls vi. SA had higher cortisol awakening responses compared to WC. First trimester waking cortisol was an independent predictor of glycaemia in the third trimester. Despite significantly lower BMI, SA had similar glucocorticoid (GC) excretion to WC. Urinary GC excretion was independently predicted by maternal adiposity and not BMI in SA. Conclusion: This research addresses important gaps in the literature in gestational diabetes in SA. There are important ethnic differences in the impact of maternal diabetes and gestational diabetes on BW and fetal growth, and evidence of early increase in adiposity at the expense of lean body mass in SA. This research provides novel evidence to support the argument for ethnicity tailored management of GDM. Our research also provides novel evidence for disordered HPA activity as a possible mechanism for the increased glycemic risk in SA. Larger randomized prospective studies incorporating offspring outcomes in relation to HPA are needed.

Polycystic Ovary Syndrome (PCOS) is a complex disorder encompassing reproductive and metabolic dysfunction. Ovarian hyperandrogenism is an endocrine hallmark of human PCOS. In animal models, PCOS-like abnormalities can be recreated by in utero over-exposure to androgenic steroid hormones. This thesis investigated pancreatic and adrenal development and function in a unique model of PCOS. Fetal sheep were directly exposed (day 62 and day 82 of gestation) to steroidal excesses - androgen excess (testosterone propionate - TP), estrogen excess (diethylstilbestrol - DES) or glucocorticoid excess (dexamethasone - DEX). At d90 gestation there was elevated expression of genes involved in β- cell development and function: PDX-1 (P < 0.001), and INS (P < 0.05), INSR (P < 0.05) driven by androgenic excess only in the female fetal pancreas. β- cell numbers (P < 0.001) and in vitro insulin secretion (P < 0.05) were also elevated in androgen exposed female fetuses. There was a significant increase in insulin secreting β-cell numbers (P < 0.001) and in vivo insulin secretion (glucose stimulated) (P < 0.01) in adult female offspring, specifically associated with prenatal androgen excess. At d90 gestation, female fetal adrenal gene expression was perturbed by fetal estrogenic exposure. Male fetal adrenal gene expression was altered more dramatically by fetal glucocorticoid exposure. In female adult offspring from androgen exposed pregnancies there was increased adrenal steroidogenic gene expression and in vivo testosterone secretion (P < 0.01). This highlights that the adrenal glands may contribute towards excess androgen secretion in PCOS, but such effects might be secondary to other metabolic alterations driven by prenatal androgen exposure, such as excess insulin secretion. Thus there may be dialogue between the pancreas and adrenal gland, programmed during early life, with implications for adult health Given both hyperinsulinaemia and hyperandrogenism are common features in PCOS, we suggest that their origins may be at least partially due to altered fetal steroidal environments, specifically excess androgenic stimulation.