This doctoral thesis by prospective publication aims to provide pragmatic, evidence-based guidance for the development and evaluation of physiological breech skills and services within the context of contemporary maternity care. The research uses multiple methods to explore development of professional competence and expertise. While skill and experience are acknowledged in multiple national guidelines as important safety factors in vaginal breech birth, prior to this research no guidance existed about how skill and experience should be defined, developed and evaluated. The thesis begins with an integrative review of the efficacy of current breech training methods, highlighting a lack of evidence associating any training methods with improved outcomes for breech births. Following this are two papers reporting the results of a Delphi consensus technique study involving a panel of breech experienced obstetricians, midwives and service user representatives. The first outlines standards of competence, training components and volume of experience recommended to achieve competence and maintain proficiency in upright breech birth. The second outlines principles of practice for physiological breech birth, rooted in relationship and response, and divergent from medicalised practices based on prediction and control. Following this is a grounded theory paper exploring the deliberate acquisition of breech competence among midwives and obstetricians with moderate upright breech experience. The paper reports a theoretical model that can inform development of breech teams and training programmes. The final paper reports a mixed methods analysis of data from the Delphi and grounded theory studies concerning breech expertise. The results present a model of generative expertise, underpinned by affinity, flexibility and relationship, which may function to increase the availability and safety of vaginal breech birth. Each paper is followed by critical analysis and reflection. The thesis ends with a discussion of the implications for practice and research in light of the overall body of work.

In the two decades since the use of ultrasound was first applied to the problems of obstetrics, its role has expanded dramatically, and, in good hands it may now be considered to be one of the most important diagnostic aids available to the obstetrician. In 1972 however, when the work described in this thesis was initiated, the ultrasonic techniques employed in early pregnancy were either subjective, or their limits of accuracy, in such areas as fetal heart movement detection and the estimation of gestational age, were less than optimal. Thus, the objectives of this study were: to develop a reliable method of detecting fetal life earlier in the first trimester of pregnancy; to devise objective criteria for the early diagnosis of unsuccessful pregnancies; and to develop a more accurate means of estimating the gestational age of a pregnancy in the first trimester. In pursuit of these objectives a "second generation" ultrasound equipment was used, the Diasonograph NE4102, an equipment which is more sophisticated electronically than earlier models, and which has many novel and useful facilities. Using this equipment three new ultrasonic techniques were developed: a combined B-, A-scan method for detecting small movements of the fetal heart; a system for estimating the volume of the gestation sac; and a technique for the measurement of the fetal crown-rump length (CRL). The technique devised to detect early fetal heart movements was based on the principle of first locating the fetus on a two-dimensional B-scan image, then examining the fetal echoes closely on an expanded uni-dimensional A-scan display. In this way it proved possible to detect movements of the fetal heart structures with reliability from seven weeks of amenorrhoea, and on occasion from as early as six weeks. Conversely, absence of such movements proved reliable as a means of diagnosing early fetal death, and with increasing confidence in the technique, patients were offered an elective termination of pregnancy, at times, on the sole evidence of the ultrasound examination. Two techniques were developed with a view to obtaining objective, and more accurate estimates of gestational age in the first trimester. These were gestation sac volume, and CRL measurements, of which the latter has proven to be relatively simple in its application, to be reproducable, and to give an accuracy of ± 4.7 days in 95 per cent of cases. This figure was confirmed in a large clinical "blind" trial. After correction for the systematic errors of the technique (1 mm plus 3.7%), the mean CRL growth curve, derived from 424 measurements, correlated well with the data published by some embryologists, but not with those by others. The possible reasons for these discrepancies are discussed. Using CRL measurements as a baseline, the accuracy of clinical bimanual estimation of uterine size in the first trimester, and of biparietal diameter measurements at approximately 20 and 36 weeks, was assessed in a further "blind" trial. The 2SD limits of each of these estimations were found to be ± 25.5 days, ± 11 days, and ± 30.4 days respectively. In view of this, and the desirability of having a reliable estimate of the gestational age in the modem management of pregnancy, it is recommended that at least all patients with "at risk" pregnancies, together with those whose menstrual histories are in any way unreliable, should be referred for an ultrasound examination at the time of their first antenatal clinic visits. It is concluded that the application of these three techniques allows a more objective and more reliable evaluation of early pregnancy and of its complications than was hitherto possible.

Uterine fibroids are common benign tumours in women. The effect they have can range from pressure symptoms and heavy menstrual bleeding to denying a woman a successful pregnancy. Despite the overall benign classification of fibroid, it is undeniable that the reduced quality of life these tumours cause may exceed the effect that some early stage gynecological cancers have on a suffering woman. There has been extensive research into treatments for fibroids however this has only resulted in a handful of worthy advances which are not proportionate to the impact these “benign” tumours have on a suffering woman. The mechanism for how fibroids affect the endometrium and cause heavy menstrual bleeding is understudied. Some of this research has pointed towards vascular endothelial growth factor and cyclooxygenase as potential mediators that change the perceived heaviness –amount and length- of a menstrual period in a woman with fibroids. Uterine artery embolisation (UAE) has emerged as a lesser invasive option and an alternative to surgery. The reported high technical success of the procedure independent of BMI and the short hospital stay and quick recovery has made it an attractive treatment modality. However, the mechanism of how it works is still not understood. Women with large variation in uterine size and fibroid number and size are undergoing this procedure without the full knowledge of how they will individually respond. This thesis aims to explore the mechanism of how UAE works by looking at the change in expression of VEGF, COX-2 & Ki67 and also the change in microvascular density of the endometrium post UAE. Our aim was to investigate how women with different sized fibroid uteri would respond to UAE and if DWI MRI had any advantages above standard MRI in predicting the outcome of UAE.

Background: Neoadjuvant chemotherapy (NAC) is being used as first line treatment in women with large and locally advanced breast cancers (LLABCs). However, the response to NAC is difficult to predict. Growing evidence suggests that these patients are immunosuppressed and that circulating immunosuppressive regulatory cells and humoral factors affect the response to NAC. We explored the possible role of the in situ tumour immune milieu in inducing and affecting the responses to NAC, and the contribution of concomitant systemic circulating regulatory cells. Methods: Paraffin-embedded breast cancers and ipsilateral axillary lymph nodes (ALNs) from pre- and post-NAC samples of a cohort of 33 women with LLABCs, 16 of whom had their blood regulatory cells previously investigated. Various immune cell infiltrations and expression of cytokines/biological molecules in the specimens were studied using appropriate monoclonal antibodies and immunohistochemistry. Statistical analysis was carried out using non-parametric tests with SPSS version 21. Results: High levels of pre-NAC tumour-infiltrating lymphocytes (TILs) (p < 0.001) and subsets of CD4⁺T cells (intratumoural, p=0.023; peritumoural, p=0.001), CD8+T cells (intratumoural, p=0.008; peritumoural, p=0.002) and CD56⁺NK cells (intratumoural, p=0.001; peritumoural, p < 0.001) were significantly associated with a pathological complete response (pCR). High levels of CD163⁺macrophages were also significantly associated with a good pathological response (p=0.004) and pCR (p=0.008). There was a positive correlation between the CD8:FOXP3 ratio and grade of pathological response. In multivariate analyses, TILs and peritumoural CD56+NK cells were found to be independent predictive factors for pCR. There was a significantly high expression of IL-10 in post-NAC breast specimens with poor responses to NAC (p < 0.001). NAC significantly reduced infiltrating T regulatory cells (Tregs) (p=0.001) and PD1⁺T cells (p=0.005), as well as expression of IL-4 (p=0.016). There was no significant difference between the percentages (%) of immune cells present in ALNs with or without metastases but there was a T helper-2 cytokine polarisation in metastatic ALNs. Metastatic ALNs with a high % of CD8+T cells (p=0.048) and low % of FOXP3+Tregs (p=0.019) were significantly associated with an ALN pCR. There was a significantly positive correlation between circulating and intratumoural infiltrating Tregs following NAC (p=0.003). Conclusions: The tumour immune microenvironment is a key factor in achieving a good pathological response with NAC. Tumour and blood immune parameters may be clinically useful in identifying women with LLABCs likely to respond to NAC. Our findings also suggest that the beneficial effects of NAC are mediated via modulation of anticancer immunity, in particular by reduction of T regulatory cells and immunosuppressive humoral factors.

Background: Maternal mortality and morbidity still pose a significant challenge in Sudan, where no significant improvements in maternal health have been achieved despite the focus on the Millennium Development Goals. Under-utilisation is a major public health concern even though Sudan is among the African countries that have registered poor maternal and child health. Health services in Sudan are generally limited and with poor quality and disparate access. Therefore, there is a need for better understanding of the barriers to the provision and utilisation of maternal health services in order to improve the health and survival of Sudanese mothers. Objectives: This study sought to assess the maternal health system functions and influences on utilisation as well as the social, cultural, and women’s characteristics that may constitute barriers to utilisation. Methodology: The study used an explanatory sequential mixed-methods design. A comprehensive analysis was conducted using several quantitative and qualitative data sets, guided by a new framework, the Maternal Health System Performance framework (MHSP) developed as part of this work in order to assess both the three objectives and four functions of the health system on both macro and micro levels. Findings: The study findings provide clear evidence that the Sudan health system is not currently capable of achieving an adequate level of attainment of the health goals or equitable distribution, due to dysfunction of the four health system functions. In addition, the findings draw attention to the important role of the stewardship function in health system performance. This function can play a key role in health system reform, as it influences management of the health system and should work across all elements of the system to ensure a well-functioning health system and efficient use of resources. The findings also underline the important role of health system related factors rather than simply population factors (such as individual, household, and community factors) in the low service utilisation among women in poor settings. While it shows that certain population characteristics such as household income and education do have a significant impact on the utilisation, the health system functions, and in particular the stewardship function, are also demonstrated to be of considerable importance. Implication: These findings have implications for policy and practice, indicating that simply blaming women for not using maternal health services is unhelpful and inappropriate and indicate that decision makers should focus more fully on improving the performance of the health system. According to the comprehensive assessment of the health system performance, the study proposes several recommendations for each health system function to enhance the performance in the context of limited resources, ultimately to improve women’s and community health in Sudan.

Dystocia refers to slow progress in the first stage of labour. The incidence in nulliparae is 20% and if untreated can lead to maternal and neonatal morbidity. Augmentation of labour to prevent and treat dystocia includes amniotomy and intravenous syntocinon. However, the optimal timing of such intervention is controversial, and leaves little scope for maternal choice, which underpins current maternity care. The literature on the physiology of labour indicates that it is a complex process, which is not fully understood. The onset and progress of labour is defined in terms of precise cervical dilations, however it is likely that there is a range of dilations consistent with 'normal' labour. The current definition of dystocia may be too restrictive and a management option, which delays obstetric intervention, might facilitate greater opportunity for normal progress. The hormonal pathways that regulate labour have some commonality with those of the stress response. This thesis presents a study designed to examine whether labouring in water, a management option that may alleviate some of the stress of labour, in particular that due to pain, might also facilitate labour progress, and affect the key labour outcomes of epidural analgesia and operative delivery. The limited literature on labouring in water suggests it is an appropriate care option for nulliparae who are at low risk of complications. Labouring in water has been associated with a reduction in pharmacological analgesia, however there were no studies involving women with dystocia. Prior to initiating a full randomised controlled trial to test the effect of labouring in water on labour outcomes for women with dystocia, a two part feasibility study was undertaken. A pilot randomised controlled trial indicated that it was feasible to conduct the planned study in the clinical area but with two trial arms (water and augmentation), instead of the proposed three arms, (water, conservative, and augmentation). A case audit formed the second part of the feasibility study. Data were used to estimate the incidence of dystocia, likely accrual rates, the potential magnitude of any change in epidural analgesia and operative delivery rates, and the required sample size for the main study. The main RCT was conducted during 1999 and 2000. A case audit over the same timeframe provided comparative data and monitored concurrent changes in practice. The epidural analgesia rate was 47% in women allocated to labour in water compared to 66% in women in the augmentation arm (OR 0.46, 95%CI 0.20 to 1.03. P=0.56). There was no difference in the operative delivery rates for women allocated to labour in water compared to those who were not. There was a significant reduction in obstetric interventions (OR 0.10 , 95% CI 0.22 to 0.49, P=0.000). The main limitation of the trial was a lower than expected recruitment rate, with 99 women being randomised compared to the intended 220. This was partially due to changes in practice during the second year of the trial. Despite the small sample, the implications for practice include the need for further consideration of more flexible definitions for labour onset and progress, and the use of labour in water for women as a supportive management option where a delay in obstetric intervention is advocated.

The prevalence of childhood atopic diseases (eczema, asthma, allergies, hay-fever) has increased during the last 30 years. Epidemiological studies link higher fish intake during pregnancy with lower risk of atopy in the offspring. Oily fish provide the long chain (LC) n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as vitamin D and antioxidants (selenium). Fish oil provides EPA and DHA and fish oil supplementation during pregnancy alters offspring immunity in a way that would be consistent with lowered risk of atopy. There are no studies of oily fish intervention in pregnancy. The Salmon in Pregnancy Study (SIPS) is the first randomised controlled trial of oily fish intervention during pregnancy. The main outcome measures of SIPS were the clinical signs of atopy in the offspring (not reported here). The current thesis presents and discusses results of SIPS mainly relating to the mother. The hypotheses examined here are that increased oily fish consumption during pregnancy will: a) increase maternal LC n-3 PUFA intake b) increase maternal LC n-3 PUFA status, c) alter maternal immunity, which may influence the developing foetal immune system in a way that would decrease atopy risk for the offspring. Pregnant women (n = 123) with high risk of having atopic offspring and with low habitual intake of oily fish (≤ 2/month) were randomised at 20 weeks of pregnancy to either consuming 2 portions/week of farmed salmon (n = 62) or continuing their habitual diet (n = 61) until the end of pregnancy. The women attended a clinic at weeks 20 (n = 123), 34 (n = 110), and 38 (n = 91) of pregnancy at which fasting blood samples were collected for fatty acid and immunological analysis, and a food frequency questionnaire (FFQ) was administered (at 20 and 34 weeks). At delivery, placenta and umbilical cord tissue were collected for fatty acid analysis. Mothers were followed-up at 3 months postpartum when the FFQ was administered (n = 88). Maternal plasma, peripheral blood mononuclear cell (PBMC), placenta nad umbilical cord tissue fatty acid compositions were determined by gas chromatography (GC). Maternal immune cell subsets were determined by flow cytometry (FACS); ex-vivo cytokine production by PBMC in response to stimulants (allergens, mitogen, and toll-like receptor (TLR) ligands) was determined by cytometric bead array (CBA) and FACS; and eicosanoid (prostaglandin (PG) E2) production by PBMC was determined by enzyme-linked immunosorbent assay (ELISA). Subjects complied with the salmon intervention and this increased their intakes of EPA, DHA, vitamin D and selenium. The salmon intervention prevented the pregnancy-associated depletion in LC n-3 PUFA and resulted in higher LC n-3 PUFA status in maternal plasma, maternal PBMC, placenta and cord tissue. Effects of pregnancy on many of the immune parameters assessed here were identified. However, the salmon intervention had only limited impact on maternal immunity as measured here, and thus it cannot be concluded whether the intervention would have an effect on the immune system of the offspring

No description available.

This research compared midwife-led with obstetrician-led antenatal care for women who had previously given birth by Caesarean section (CS) and had no other risk factors. The primary outcomes under investigation were intended and actual mode of birth. Safety outcomes were also evaluated and compared. Internationally, CS rates have risen dramatically over the last three decades. There is large variation between rates in different maternity units. Vaginal birth after Caesarean (VBAC) is considered a safe option for the majority of women who have a previous CS. Evidence suggests that factors in antenatal care can influence women’s mode of birth decision, most notably the interaction with health professionals. Midwife-led care is known to have benefits for ‘low-risk’ women; it is argued that these benefits can be extrapolated to women whose only risk factor is a prior CS. This research was a retrospective, comparative cohort study. A quantitative methodology was applied to objectively compare intended and actual VBAC rates between women who received either midwife-led or obstetrician-led antenatal care. Women’s case-notes were reviewed and data collected (n=405). The sample size was calculated to test a non-inferiority hypothesis: that midwife-led antenatal care elicits a VBAC rate that is equal to or higher than obstetrician-led. Analysis indicates that receiving midwife-led antenatal care resulted in higher intended and actual VBAC rates compared with obstetrician-led antenatal care: 90% vs. 77%, OR 2.78 (95% confidence interval 1.57-4.92), p<0.001 and 61% vs. 47%, OR 1.79 (1.2-2.66), p=0.004, respectively. These findings remained significant after adjustment for clinically important confounding factors. Analysis also provides some evidence that midwife-led antenatal care is safe and results in fewer episodes of unscheduled antenatal care and antenatal inpatient admissions. Significant improvements were demonstrated with midwife-led compared to obstetrician-led antenatal care with regard to continuity of carer, the environment of care and the time women had to make their mode of birth choice. It is theorised that these differences, the organisation’s support of the innovation and, perhaps most importantly, the midwifery expertise and focus on normal birth increased the VBAC rate by enhancing women’s confidence in their ability to birth naturally. This research has demonstrated an association between midwife-led antenatal care and increased VBAC rates and has provided some evidence that this type of care is safe.

A high fat (HF) diet leads to hypercholesterolemia and predisposes the individual to developing cardiovascular disease (CVD). We hypothesised that mother‘s HF diet before and during pregnancy and lactation can also influence predisposition to CVD in offspring fed a similar diet. The thesis sets out to investigate whether (1) the effects of long-term consumption of a HF diet by the mother predisposes her offspring to developing a CVD/ metabolic syndrome in adult life and (2) pharmacological intervention using statin alleviates the detrimental effects of maternal HF diet on the health of the dams and their offspring. Female C57BL/6 mice were fed either a HF diet (45% kcal fat) or standard chow (C; 21% kcal fat) from weaning through pregnancy and lactation. Pregnant C57/BL6 mice on HF diet were further given pravastatin in the drinking water (5 mg/kg of body weight per day) either short-term (2nd half of pregnancy and during lactation) or long-term (from weaning through to pregnancy and lactation) to lower cholesterol and improve post-weaning maternal blood pressure. Weaned female offspring from each group were then fed either a HF or C diets to adulthood. Body weight, blood pressure, plasma cholesterol, C-reactive protein (CRP) and bone marrow derived endothelial progenitor cells (EPC) were measured at 24, 28 and 36 weeks post-weaning in different experiments. Histology of the liver and kidneys were performed. Offspring from hypercholesterolemic mothers on HF diet were significantly obese (bodyweight in grams; 17.2+4.2 vs. 13.8+4.7; P<0.05), hypertensive (SBP mmHg; 134+4.2 vs. 117+3.4; P<0.001), less active (distance in cm; 312 + 31 vs. 563 + 45; P<0.001), demonstrated increased lipid laden vacuoles in liver and kidneys; and showed reduced expression of EPC (P<0.05) than offspring from C dams independent of their postnatal nutrition respectively. Pravastatin therapy in HF mothers resulted in abrogation of these variables in offspring independent of post weaning nutrition (P<0.05). The effects were more permanent when the dams were given long-term statin treatment. The study demonstrates that long-term maternal HF feeding from weaning through pregnancy and lactation predisposes offspring to hypertension, raised plasma lipids, fatty liver, kidney disorders, raised CRP and inhibition of EPC numbers and expression in offspring. Pravastatin treatment of these dams inhibits these effects on the offspring and may reduce their risk of later cardiovascular pathophysiology. The findings may have implications for understanding the effects of the ‗nutritional transition‘ to higher dietary intake of fat which could lead to increased cardiovascular disease in many societies.