<strong>Background and objectives:</strong> The incidence of preterm birth (PTB), and the extent to which it results in perinatal mortality in sub-Saharan Africa (sSA) is unclear, partly because reliable estimates of gestational age (GA) at birth are lacking. This research: 1) Describes how clinical and ultrasound (US) estimates of gestational age (GA) influence PTB rates and perinatal mortality amongst a population in Kilifi, Kenya; 2) Implements a novel PTB classification system as proof of concept that such systems are feasible in low-income settings, and 3) Presents two novel approaches for estimating GA for women presenting >24 weeks’ gestation. <strong>Methods:</strong> Objectives 1) and 2) used a perinatal surveillance platform developed at the KEMRI/Wellcome Trust Research Programme in Kilifi, Kenya. Ultrasound (US) was offered for GA estimation in women ≤24 weeks’ gestation clinically. To achieve objective 3), two candidate US dating equations were derived by combining a machine learning algorithm with polynomial regression analyses. Lastly, an entirely automated model with the capacity to estimate GA using computational image analysis of the fetal cerebral cortex was developed and tested. <strong>Results:</strong> 1) Between November 2011 and July 2013, 3630 women presented for antenatal care, 1107 women had US and data were available for 950 (86%) of these. The PTB rate by US (US-GA) was 10.0% compared to 17.1% by a best clinical estimate of GA (C-GA), although the number of perinatal deaths that were preterm by US and C-GA were similar; 2) Implementation of a novel PTB classification system is feasible, and 3) New dating equations and an automated model provide estimates in the 3rd trimester with a prediction error at 34 weeks of 12.4 and 14.2 days, respectively. <strong>Conclusion:</strong> Clinical estimates of GA significantly overestimate the rate of PTBs. Despite this, the proportion of perinatal deaths in those identified as preterm by clinical and US methods was similar, suggesting that US may be a better predictor of PTB and its associated mortality. Novel dating methods can estimate GA at 34 weeks’ gestation with an error equivalent to that provided by routine clinical methods at 22 weeks’. This has important implications and may extend capacity to provide GA estimates amongst a large group of women whose birth phenotypes remain poorly described.

In the United Kingdom (UK) there is easy access to a wide range of contraceptive methods, available at no cost. In addition, oral emergency contraception (EC) (1.5 mg levonorgestrel) is now widely available from the community pharmacy. In spite of this, unintended pregnancy is common. In 2014 in England and Wales, 184,571 induced abortions were performed, and in Scotland, the corresponding figure was 11,475. Long acting reversible methods such as contraceptive implants and intrauterine contraception, are amongst the most effective methods available and National Institute for Health and Care Excellence (NICE) recommends that increased uptake can lead to fewer unintended pregnancies. However, uptake of long acting reversible contraceptive (LARC) methods remains low. The majority of women who require to use EC do so following unprotected sex or an accident with a condom. Increasingly women in Great Britain prefer to attend a pharmacy for EC rather than a sexual and reproductive health (SRH) service or general practitioner (GP). Starting an effective on-going method of contraception after EC use is clearly important if women are to avoid unintended pregnancy. Community pharmacists in the UK and most other high income countries are usually unable to provide any on-going contraception except condoms. So we have created a situation where EC is provided almost solely from settings where other more effective methods of contraception cannot be immediately provided. Novel strategies are therefore required to facilitate both uptake and continuation of the most effective methods of contraception, in order to prevent unintended pregnancy for more women. This thesis presents a mixture of biomedical, clinical and health services research to evaluate a series of strategies aimed at improving uptake of the most effective methods of contraception. Two studies investigated patient knowledge and information provision relating to contraceptive methods. The first sought to determine if women held misconceptions about intrauterine methods of contraception, and revealed that although myths persist in a small number of women, a lack of knowledge about these methods was also evident. The second study aimed to determine if the use of a digital video disc (DVD) to provide contraceptive information was acceptable and informative to women, and identified that it is, and could possibly enhance patient consultations. Studies three, four and five investigated strategies aimed at increasing the uptake of effective on-going contraception, following emergency contraception provided from a community pharmacy, and patient and health care provider attitudes to such approaches. They showed that simple interventions such as supplying one month of a progestogen only pill (POP), or offering rapid access to a family planning clinic (FPC), hold promise as strategies to increase the uptake of effective contraception after EC and that both women and clinicians were positive about such measures. Additionally, the problems encountered in conducting these studies provided valuable feedback to inform further development of research methods in the community pharmacy setting, and larger scale studies of such interventions. Community SRH services may be well placed to deliver more abortion care in the UK, and consequently this may result in greater uptake of contraception post abortion. Study six aimed to determine the views of health professionals working in SRH regarding their attitudes towards providing more abortion services and also the views of staff within one community SRH centre in Scotland where a service providing early medical abortion was due to commence. It showed there is clear support amongst health professionals in community SRH in the UK towards greater participation in provision of abortion care services.

I investigated the role of genetic, environmental and intrauterine factors in child development using data from two large twin studies; the East Flanders Prospective Twin Survey (EFPTS) and the Twins and Multiple Births Association Heritability Study (TAMBAHS). An association between birth weight and child development has already been established. Potential associations between other factors of the intrauterine environment and child development were investigated in this thesis. Heritabilities of the umbilical cord, IQ, temperament and behaviour problems were estimated. Fetal characteristics, such as birth weight, placental weight and morphology, umbilical cord knots, length and insertions were investigated in relation to cognitive development in the EFPTS study. The impact of maternal pre-pregnancy weight on temperament and behaviour problems was examined in the TAMBAHS study. High heritability estimates were observed for certain dimensions of the umbilical cord, temperament and IQ; for behaviour problems, genetic, shared and non-shared environment were important. Low birth weight and cord knotting was associated with lower IQ; an association was observed between maternal overweight and children aggressive behaviour. The results are discussed in the context of the Developmental Origins of Health and Disease (DOHaD) hypothesis, highlighting the role of the intrauterine environment in child development.

Bibliography: leaves 230-294. / xiii, 294 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Analyses in detail a native small fragment of hCG/[beta] hCG subunit, the [beta]-core hCG fragment which is found in large amounts in urine and may be of clinical importance. The aims were to purify the fragment, analyse its protein and carbohydrate structure, develop direct assay methods for its measurement, and to examine it's distribution in body fluids and it's relationship with the intact hCG molecule during pregnancy. / Thesis (Ph.D.)--University of Adelaide, Dept. of Obstetrics and Gynaecology, 1993

The prevalence of maternal obesity is on the increase, compromising both maternal and foetal health. Previous intervention studies have been designed to limit the amount of gestational weight gain but in the absence of UK guidelines relating to optimum weight change in obese pregnancies and the negative experiences of obese women with regard to previous weight loss attempts it is reasonable to ask whether this is the most effective approach. It has been demonstrated that maternal dietary intake can impact on gestational weight gain and birth weight but there is little in the way of research into the impact that quality of diet has on outcomes. Aims: To measure the quality of maternal dietary intake and weight change against pregnancy and birth outcomes and to explore and gain insight into the lived experience of obese pregnant women with a view to informing guidelines. Methods: Pregnant women with a BMI≥35kg/m2 were recruited from antenatal clinic and asked to complete 3 day food diaries at 16,28 and 36 weeks gestation, The diaries were verified using a food atlas and analysed using Microdiet. A subset of women were then followed up and interviewed regarding their lived experience of obesity. Results: The women’s dietary intake deteriorated over the duration of pregnancy and there were significant associations between some micronutrients and pregnancy and birth outcomes. Women with a BMI 35-39.9kg/m2 were most likely to gain weight. Conclusion: The dietary intake of obese pregnant women is an important predictor of pregnancy and birth outcomes and it was demonstrated that the quality of diet significant deteriorated over the duration of pregnancy. Interventions designed to increase the quality of diet are urgently required.

Background In 2014, 27.0% of births in England and Wales were to mothers born outside of the UK. Compared to their white British peers, minority ethnic and migrant women are at a significantly higher risk of maternal and perinatal mortality, along with lower maternity care satisfaction. Although existing literature highlights the importance of midwife-woman relationships in care satisfaction and pregnancy outcomes health professionals report difficulty in providing services to minority ethnic and migrant women. However little research has explored the factors contributing to the midwife-woman relationship for migrant and minority ethnic women. Research Aims To explore relationships between migrant Pakistani women and midwives in South Wales; focusing on the factors contributing to these relationships, and the ways in which these factors might affect women’s experiences of care. Method A focused ethnography in South Wales; semi-structured interviews with 10 migrant Pakistani participants (eight pregnant women, one husband and one mother) and 11 practising midwives, fieldwork in the local migrant Pakistani community and local maternity services, observations of antenatal booking appointments, and longitudinal reviewing of relevant media outputs, such as UK news reports of issues relating to migrant people. Data were analysed concurrently with collection using thematic analysis. Findings The midwife-woman relationship was important for participants’ experiences of care. A number of social and ecological factors influenced this relationship; including family relationships, culture and religion, differing healthcare systems, authoritative knowledge, and communication of information. However, differences were seen between midwives and women in the perceived importance of these themes. Findings therefore suggest that in order to understand how midwife-woman relationships are created and maintained, more needs to be done to recognise and address these differences. Due to the complexity of the relationships between themes a social ecological model of relationships is forwarded as a means of visually capturing the complexity of the findings, as well as potentially shaping midwifery education and clinical midwifery practices. Conclusions and Implications Findings from this study provide new theoretical insights into the complex social and ecological factors at play during maternity care for migrant Pakistani women. These findings can therefore be used to create meaningful dialogue between women and midwives, encourage collaborative learning and knowledge production, and facilitate future midwifery education and research.

My research explored student experiences of becoming midwives. It focused specifically on understanding their lived world experiences. The research is located in a hermeneutic framework as described by van Manen (1990). I chose to undertake a longitudinal study as the length of the students’ course of study was three years. My study recruited two cohorts of student midwives from two universities in the North West of England (n=90). Each university had a different recruitment target for their midwifery programme of study; University A (n=60), University B (n=30). I prepared a PowerPoint presentation and an information leaflet which supported the recruitment strategy (Appendix B). My approach proved successful as the study originally consisted of a purposive sample of student midwives (n=22); University A (n=10) which equated to 20% of the cohort and University B (n=12) equated to 33% of the cohort. Four students from University B dropped out of the research following the first focus group, thereby reducing the total sample to 18. This reduced the sample size of university B (n=8) which equated to 27% of the cohort. My use of narrative inquiry within focus groups enabled a hermeneutic cyclical process of gathering and interpreting the student holistic experiences in a constructivist paradigm (Clandinin and Connelly, 2000). I also used reflective diaries which enabled the students to reflect on their personal experiences. This added richness to the empirical data (Berg, 2009). The interviews were recorded and transcribed verbatim. Thematic analysis was undertaken using the principles of van Manen (1990). I gained ethical approval from LJMU and the two universities where the students were studying. The aims of my research directed the focus of the study. Discovering their interpretations of their experiences of becoming midwives brought an understanding of the influences the working environment had on the process. The findings of my study brought new knowledge in respect of the education of student midwives. It also highlighted some of the restrictions imposed on their training within a medical model of care in an NHS Trust. The research also highlighted some of the challenges experienced by the students as they progressed through their training. The findings suggested there were many tension experienced by the students. The broad themes were related to: the students’ understandings of their learning and development, the ideology of the role of the midwife and the role of the midwife within the philosophy of the medical model of care in NHS Trusts. This brings new knowledge in respect of the education of student midwives.

Le développement de nouvelles stratégies de prise en charge de la MAP constitue un enjeu important de Santé Publique, la seule stratégie disponible reposant sur l’inhibition des contractions utérines par les tocolytiques. Bien que les mécanismes physiopathologiques de la MAP restent mal élucidés, il a été établi que l’induction du travail s’accompagne d’une transition des cellules myométriales d’une phase proliférative vers une phase contractile. Dans nos travaux, nous nous sommes intéressés aux effets de la leptine sur la prolifération et la différenciation des cellules myométriales. Nous avons mis en évidence que la leptine est capable d’induire une prolifération cellulaire, associée ou non à l’induction d’une signalisation pro-inflammatoire. En effet, nous avons démontré que la leptine à 50 ng/ml est capable d’activer la voie pro-inflammatoire IL-6R/NFkB, jouant un rôle dans la mise en route du travail alors que la leptine à 6.25 ng/ml stimule la voie OB-R/ERK1/2, en faveur de la prolifération. De plus, des résultats préliminaires ont suggéré que la leptine à 6.25 ng/ml est capable de s’opposer à la différenciation des cellules myométriales alors que la leptine à 50 ng/ml induit une réorganisation du cytosquelette, une synthèse des protéines COX2 et Cx43, ainsi qu’une augmentation de l’influx calcique, étapes indispensables à la genèse de contractions. Ce travail apporte un argument supplémentaire en faveur d’un potentiel rôle de la leptine dans la prévention de la MAP, en maintenant les cellules dans un état prolifératif et en s’opposant à leur différenciation. De plus, ce travail fournit de nouvelles informations quant à la compréhension des différents troubles de l’accouchement observés chez les femmes obèses – dépassements de terme ou accouchements prématurés - ayant été mise en évidence. / Maternal obesity is associated with a wide spectrum of adverse pregnancy outcomes leading to higher rates of postdate pregnancies or preterm deliveries. Finding new strategies for the management of the Threat of Preterm Labor (TPL) is an important Public Health issue. Indeed, the only available strategy (tocolytic drugs) inhibiting uterine contractions, does not allow delaying parturition for more than 48 hours. The physio-pathological mechanisms leading to TPL remain poorly understood, but it has been shown that labor onset is associated with a phenotypic switch of myometrial smooth muscle cell from a proliferative to a contractile phenotype. In this work, we investigated the effect of leptin, an adipokine synthesized by the placenta during pregnancy and that has been proposed for the management of preterm labor, as it is able to prevent in vitro uterine contractility, on human myometrial cell proliferation and differentiation. In this work, we demonstrated that leptin induces myometrial proliferation, with or without the induction of pro-inflammatory signaling. Indeed, we highlight that leptin at 50ng/ml is able to activate IL-6R/NFkB pro-inflammatory pathway described to play a role in the onset of labor while leptin at 6.25 ng/ml stimulates OB-R/ERK1/2 signaling pathway, leading to proliferation. In addition, preliminary results on cell differentiation have suggested that leptin at 6.25ng/ml is able to oppose this transition, whereas leptin at 50ng/ml induces cytoskeletal reorganization, COX2 and Cx43 protein expression and increased calcium influx, leading to effective myometrial contractions. Finally, this work emphasizes the potential value of leptin in the pharmacological management of TPL and it also strengthens the hypothesis that leptin might be a contributory factor in the delivery disorders observed in obese women.

Le rôle du fibrinogène dans les coagulopathies par hémorragie a fait récemment l'objet de travaux importants, la plupart hors du champ obstétrical. L'adaptation de la coagulation et du fibrinogène au cours de la grossesse est méconnue même si sa mise en jeu paraît indispensable à l'hémostase utérine lors de la délivrance. Nous avons donc étudié les modifications gestationnelles du fibrinogène et analysé leurs impacts sur la coagulation et l'hémorragie de la délivrance (HDD). Nous avons montré que le fibrinogène augmentait progressivement pendant la grossesse pour atteindre [3,5-6,5 g/L] (5ème-95ème p.) au 3ème trimestre. L'étude en thromboélastométrie (TEM) a révélé une élévation progressive du "potentiel coagulant" et de la fermeté du caillot chez la femme enceinte. Nous avons ensuite analysé le lien entre le taux initial de fibrinogène lors d'une HDD et le risque d'aggravation (Etude PITHAGORE 6). Le taux de fibrinogène était le meilleur marqueur du risque d'évolution grave. Des seuils de fibrinogène inférieurs à 2 et 3 g/L étaient associés à un risque accru d'aggravation par rapport aux femmes avec un taux > 3 g/L (respectivement OR=11,99 ; IC95% [2,56-56,06] et OR=1.90; IC95% [1,16-3,09]. Enfin l'étude en TEM a montré que les paramètres précoces CA5- et CA15-FIBTEM étaient étroitement corrélés aux taux de fibrinogène lors des HDD permettant l'optimisation du monitorage de la coagulation. Nos résultats nous conduisent à proposer deux scores de coagulopathie obstétricale prenant en compte les spécificités de la grossesse. Des essais seront nécessaires pour valider la pertinence de ces scores et pour évaluer le bénéfice de la compensation précoce en fibrinogène dans les HDD / The role of fibrinogen in haemorrhage-induced coagulopathies has recently been the subject of important work, most of it outside the field of obstetrics. The changes in coagulation and fibrinogen during pregnancy are poorly understood, even though its involvement is essential for uterine haemostasis during the afterbirth. We thus studied the course of fibrinogen levels during pregnancy and analysed their effects on coagulation and postpartum (third-stage) haemorrhage (PPH). We showed that fibrinogen increases progressively during pregnancy, reaching [3.5-6.5 g/L] (5th-95th p.) during the 3rd trimester. The thromboelastometry (TEM) study revealed a progressive increase in the coagulant potential and firmness of clots in pregnant women. We then analysed the association between the initial fibrinogen level during PPH and the risk of aggravation (in the PITHAGORE 6 study). A woman's fibrinogen level was the best marker of the risk that her condition would worsen. Thresholds below 2 and 3 g/L were associated with higher risks of aggravation than in women with fibrinogen concentrations >3g/L (respectively OR=11.99 ; 95% CI [2.56-56.06] and OR=1.90; 95% CI [1.16-3.09]. Finally the TEM study showed that FIBTEM assessment of the early indicators, clot amplitude at 5 and 15 minutes (CA5 and CA15), was closely correlated with fibrinogen levels during PPH and thus helped to optimise coagulation monitoring. Our results lead us to suggest two obstetric coagulopathy scores that take the specificities of pregnancy into account. Trials will be necessary to validate their relevance and to assess the benefits of early fibrinogen replacement in PPH

Background: The differential effects of using topical oils for the prevention or treatment of baby dry skin on skin barrier function may contribute to the development of childhood atopic eczema. Prevalence of atopic eczema has increased from 5% of children aged 2 to 15 years in the 1940s, to approaching 30% more recently. This increase cannot be attributed to genetic changes. It is likely that increases stem from environmental factors, including the increased use of some inappropriately formulated commercial and natural baby skincare products. Midwives, health visitors and other maternity service health professionals, in the UK, routinely recommend the use of olive oil and sunflower oil for baby dry skin or massage, but the effect of these oils on newborn baby skin has not been studied. Aim: The aim of this research was to assess the feasibility and acceptability of testing the hypothesis that the regular application of sunflower oil, when compared to no oil or olive oil, had an effect on skin barrier function of newborn term babies. Study Design: A pilot, assessor-blinded, single centre, three-arm, randomised controlled trial, with nested qualitative component, underpinned by post-positivism. Methods: Quantitative methods were used to establish proof of concept that the use of topical oils had some effect on newborn baby skin barrier function, and to assess the feasibility of trial processes and parameters. Qualitative methods were used to explore the acceptability to parents of having a newborn baby participating in a randomised controlled trial, and trial design and procedures. The study was conducted in St. Mary’s hospital, a large teaching hospital in North West England. Data were collected between September 2013 and August 2014.The randomised controlled trial included 115 babies who were randomised to three groups: sunflower oil, olive oil and no oil, using a computer-generated varied size block randomisation with concealed allocation. Parents of babies randomised to the oil groups were blinded to which oil they were allocated. Data were collected using standardised case report forms for demographic and clinical observation data, weekly telephone questionnaires and a follow-up questionnaire, informed by previous baby skincare trials. The qualitative study encompassed semi-structured interviews, conducted within six months of birth. The sample was a subset of the trial participants, purposively sampled to incorporate a mix of treatment groups and positive and negative experiences derived from the follow-up questionnaire. Data also included two open-text questions from the follow-up questionnaire. Quantitative data were managed using IBM SPSS Statistics versions 20 and 22 and analysed descriptively. Qualitative data were managed in NVivo 10 and analysed using Framework Analysis. Results: The pilot study found that a definitive randomised controlled trial is not the optimal next step. A longitudinal observational study and further mechanistic work is recommended. Recruitment was challenging and loss to follow-up was higher than anticipated. Protocol adherence was reasonable and the study was acceptable to parents. Some statistically significant results were obtained, which must be interpreted with caution as the study was not powered to detect such a difference. These results showed that both oils may impede the development of the skin barrier function from birth; clinical importance of the results is not known. Conclusion: A longitudinal observational study is required, which maps the diagnosis of atopic eczema with environmental factors such as the use of baby skincare products from birth. Mechanistic work is also required to consider the optimal skincare formulation. As any intervention should do more good than harm, it would be wrong to support the recommendation of topical olive oil or sunflower oil for newborn baby dry skin or massage, based on the study data.