Overweight and obesity in pregnancy, alongside excessive gestational weight gain, present increased risks of adverse maternal and child outcomes. In the UK, there are no evidence-based guidelines for appropriate weight gain in pregnancy, and NICE (2008) antenatal guidance recommends weighing only at the booking-in appointment. However, in parallel with the general population, prevalence rates of overweight and obesity in pregnancy are increasing, presenting challenges to the healthcare system. NICE (2010) guidance on weight management and pregnancy have specified research recommendations to determine effective approaches to help women to manage their weight before, during and after pregnancy, and to determine whether available Institute of Medicine (2009) guidelines on gestational weight gain from the USA are suitable for use in a UK population. These research recommendations form the basis for the aims and objectives of the PhD thesis, broadly, exploring the issue of weight management before, during and after pregnancy. An exploratory approach was used to address the research objectives; qualitative interview studies were used to explore the issue of weight management and pregnancy, and routine weighing, from the perspective of health professionals, pregnant women and postnatal women. Feasibility studies were utilised to investigate approaches to raising awareness of preconception care among women of childbearing-age. Feasibility studies suggest it is plausible to raise awareness of preconception care in community pharmacy and family planning clinic settings. Qualitative research presented in this thesis found women do not report making significant changes to health behaviours in preparation for pregnancy, and health professionals viewed the preconception period as an appropriate time to target weight management. Women are concerned about their weight in pregnancy and seek out additional information on the issue, feeling health professionals are well placed to provide this support. Conversely, health professionals perceive women to be unaware of the risks associated with obese pregnancy and sensitive to having it discussed. Postnatal women who were weighed throughout pregnancy reported several benefits to the practice, suggesting the practice is acceptable to pregnant women.

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Introduction: Obesity now affects nearly 1 in 3 adults in the UK. It is estimated that 20% of pregnant women are obese. Increasing evidence associate obesity in pregnancy with susceptibility to obesity and metabolic syndrome in the child. Here an established mouse model of maternal obesity was employed to investigate energy balance and glucose metabolism in the offspring. Polydextrose (PDX) has been shown to improve glucose metabolism and, therefore may be beneficial in obese pregnancy. Hypothesis: It was hypothesised that (a) maternal obesity has adverse effects on offspring energy balance and glucose metabolism and that (b) these adverse effects will be prevented by supplementation of the maternal diet with PDX during pregnancy and lactation. Moreover, it was investigated whether PDX supplementation in obese pregnancy is protective against the adverse influences of an obesogenic dietary exposure in adulthood. Methods: Female mice were fed a control or an obesogenic diet, 6-weeks before mating and throughout pregnancy and lactation. A cohort of the obese dams was assigned to supplementation with 5% PDX in pregnancy and lactation. Maternal profiles were assessed during pregnancy. At 3 and 6-months of age offspring energy intake (EI), energy expenditure (EE) and Respiratory Exchange Ratio (RER) were measured by indirect calorimetry and glucose-tolerance-tests were performed. At 3-months the animals were challenged for 3-weeks with an obesogenic diet before re-estimation of EI, EE, and RER. Microbiota composition, mitochondria copy number and UCP gene expression was assessed as potential underlying mechanisms. Results: Maternal supplementation with PDX improved reproductive success, increased water intake and decreased markers of inflammation during gestation in the dams. At 3 months of age, offspring of obese dams (OffOb) metabolic parameters did not differ from offspring of control dams (OffCon). At 6 months OffOb were heavier (P<0.01), had lower RER (P<0.05) and lower EE (P<0.001) compared to OffCon. OffOb had impaired glucose metabolism compared to OffCon (P<0.05). Maternal supplementation with PDX prevented these defects. Following 3-weeks obesogenic dietary challenge OffObs demonstrated hyperphagia, decreased EE (P<0.05) and subsequently greater weight gain compared to controls (P<0.05), which were prevented by maternal PDX supplementation. Maternal obesity resulted in decreased mitochondria copy number at 30 days of age and altered microbiota composition at 6 months of age, which may mediate the changes observed later in life. Maternal supplementation with PDX, prevented mitochondrial dysfunction, increased the number of beneficial microbiota and the expression of UCP1 and 3 genes. Conclusions: Maternal obesity adversely influences offspring energy balance, which is prevented by maternal intervention with PDX. PDX may, therefore, provide a potential therapeutic intervention in preventing the transgenerational acceleration of obesity.

The physiological changes of pregnancy alter the pharmacokinetics of low molecular weight heparins (LMWH). The optimal dosing strategy of LMWH for the treatment of antenatal venous thromboembolism (VTE) is not known and this has led to significant variation in prescribing practice when women are managed for antenatal VTE with LMWH. The aim of this thesis is to describe the pharmacokinetics of enoxaparin during pregnancy using the method of population pharmacokinetic (PK) modelling. In addition, pregnant women’s thrombin generation and D-dimers are measured and described and their views and adherence to enoxaparin are explored. Pregnant women prescribed enoxaparin at King’s College Hospital were eligible for recruitment. Subjects (n=123) had up to 3 anti-Xa activities drawn per clinic visit (monthly), contributing 795 anti-Xa activities for PK modelling purposes. A one compartment model, with a combined error model, produced a robust enoxaparin antenatal PK model, with weight, baseline lean body weight and gestation found to be significant covariates on enoxaparin antenatal PK. Simulations from the final PK model revealed that a once daily dose of enoxaparin is appropriate in this setting. D-dimer concentrations were found to increase in line with gestation (r=0.382). Thrombin generation was also increased during the antenatal period, with enoxaparin found to influence the different thrombin generation parameters in a dose-dependent manner. Findings from the adherence aspect of this study revealed that women were highly adherent to enoxaparin antentally (mean 97.92%) and demonstrates that women are prepared to inject themselves with a parenteral medication, if they feel it is protecting theirs and their unborn baby’s health; this belief does impact on adherence to LMWH during the postnatal period, where in some women adherence drops (mean 92.75%). This study describes the pharmacokinetic profile of enoxaparin during pregnancy and provides compelling evidence for enoxaparin once daily dosing for managing antenatal VTE.

In recent years Enquiry Based Learning (EBL) has been embedded in a variety of healthcare related programmes and has become a fundamental component of curricula delivery. EBL research suggests that positive experiences outweigh limitations including enhancing links between theory and practice. Development of transferable skills such as decision making, problem solving and critical thinking is attributed to EBL in some studies. Overall however, very little high quality evidence exists to advocate EBL’s efficacy and subsequently justify widespread curriculum change. Limited research is available on the effectiveness of EBL in midwifery education, additionally there is a paucity of EBL related research with midwifery graduates, an anomaly this evaluation attempts to ameliorate. EBL was recently introduced into Higher Diploma in Midwifery education in the Republic of Ireland. As EBL is frequently credited with being positively influential on clinical practice, it was considered fitting to undertake an evaluation based on this premise. The aim of the study was to elicit perceptions of Higher Diploma in Midwifery graduates regarding the impact of Enquiry Based Learning on their clinical practice. Fourteen graduates took part in a qualitative study which used semi-structured interviews. Findings centred on three major themes: ‘Impact of EBL on the experience of learning’, ‘Impact of EBL on the quality of learning’ and the ‘Impact of EBL on clinical practice’. These three themes incorporated fourteen categories which were then used to provide the framework for discussing the research findings within the context of wider literature. Findings support the assertion that EBL helps relate theory to clinical practice as well as enhancing personal development and the quality of learning. Recommendations are made based on the findings and the implications for stakeholders in midwifery education, practice and management are discussed.

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Worldwide, there is a general lack of knowledge about medication safety during pregnancy. This problem is even greater in developing countries such as Cameroon with no epidemiological data. This PhD thesis provides data on the two arms of pharmacoepidemiological safety studies - use and risk - for anti-infectives in pregnancy. Between February and August 2015, 795 pregnant women attending 23 hospitals in SW Cameroon for antenatal (ANC) or other care were interviewed on first trimester medication use using structured questionnaires. Findings indicated that use of orthodox (73.1%) or traditional (36.9%) medications were common, with a proportion of women (28.7%) combining both. Antimalarials (33.6%) and antibiotics (20.8%) were the 3rd and 4th most commonly consumed group of orthodox medication. Sulfadoxine/pyrimethamine, contraindicated in the first trimester of pregnancy, was the most commonly used antimalarial (13%). Health unit and gestational age at ANC booking were consistent statistically significant predictors of use of different medications. In the second study, 30 congenital anomaly (CA) signals related to antibiotics use identified from the literature were tested in a case-malformed control study using the European Surveillance of Congenital Anomaly (EUROCAT) database covering 8 million births and records for 155,630 livebirths, stillbirths and terminations of pregnancy with CA. Cases were babies/fetus with CAs identified in the 30 signals, and controls were all other malformed babies/fetus. Binary logistic regression results confirmed two signals: congenital glaucoma related to general antibiotics intake (AOR2.11; CI: 1.05, 4.23); and atrioventricular septal defect related to intake of macrolides (AO2.97; CI: 1.47, 5.98). Eight new signals were generated requiring independent confirmation. The last part of this thesis combines the results from both studies to estimate the burden of CAs associated with first trimester use of antibiotics in SW Cameroon and recommends public health measures for safer use of medication in pregnancy in Cameroon.

Maternal overweight and obesity are major public health concerns which can have a significant impact on the health of both the woman and her baby. The last twenty years have seen a significant increase in the prevalence of maternal obesity within the UK, with approximately one in five pregnant women being classified as obese. To tackle maternal obesity and reduce complications, guidelines and antenatal weight management programmes have been implemented. In order to inform the planning and development of future effective programmes which may reduce/minimise negative outcomes for the woman and her baby, it is important that programmes are compared with one another. The aim of this study was to advance understanding of the core elements required in the planning, implementation and evaluation processes to maximise the effectiveness of future antenatal weight management programmes. To achieve this, a Comparative Effectiveness Review of antenatal weight management programmes was conducted; a literature review to inform the development of a conceptual framework was undertaken and a mixed-methods study carried out. The main contribution of this study was a current picture of how UK antenatal weight management programmes within maternity services and local councils were planned, implemented and evaluated. This study identified that maternity services were not meeting guidelines for the provision of an antenatal weight management programmes as one-third did not offer a programme (n=25). For those maternity services and local councils that implemented a programme (n=77), only 37.9% adhered to the recommended inclusion threshold (BMI £30 kg/m2). A significant barrier to planning, implementing and evaluating these programmes was the lack of dedicated resources. Finally, the collected data were used to test and subsequently amend the derived conceptual framework which incorporated Realistic Evaluation. This framework and study findings may inform the future effective planning, implementation and evaluation of complex health promotion programmes.

The age of childbearing is rising in women living in industrialised nations. Advanced maternal age is associated with a small increased risk of term antepartum stillbirth. Labour induction would likely reduce stillbirth, but might also increase Caesarean delivery, already high for older women. The aim of this thesis was to design and conduct a randomised controlled trial of induction of labour at 39 weeks versus expectant management for nulliparous women aged over 35 years. In total 619 women participated and the trial showed that induction of labour has no adverse short-term effects on maternal or neonatal outcomes. In particular, it does not increase caesarean section rate. A cost-utility analysis of the trial was performed and demonstrated that induction of labour is associated with a small gain in QALYs and is not more expensive than expectant management. One key secondary outcome of the trial was maternal satisfaction. There is a lack of a robust validated tool for evaluating labour experience in the UK therefore a study of 350 women was performed to validate a Swedish instrument (Childbirth Experience Questionnaire) in the UK. This study demonstrates that the Childbirth Experience Questionnaire is a valid and reliable measure of childbirth experience in the UK population. A study examining the causes of 2850 cases of antepartum stillbirth in women of advanced maternal age using anonymised national data found that stillbirths in women over 35 years old are more likely to be due to major congenital anomalies, mechanical causes, maternal disorders or associated obstetric factors than women less than 35. In 2013, a systematic review of randomised controlled trials of induction of labour versus expectant management at term found that a policy of induction was associated with a 17% reduction in the risk of caesarean section. An IPD meta-analysis of induction of labour versus expectant management at term in women with intact membranes by subgroups of maternal age has shown that induction in women of advanced maternal age has no statistically significant effect on caesarean section rates.