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Background Caesarean section (CS) rates in women experiencing stillbirth have not been studied with nationally representative data. Two Ghana Maternal Health Surveys (GMHS) have captured pregnancy and mode of birth data for all women including those with stillbirths. We compared CS rates between women with live births and stillbirths, and identified socio-economic and pregnancy-related factors associated with CS in stillbirths. Methods A population-based cross-sectional study was conducted in a pooled sample of 17 138 women who had given birth within 5 years preceding the 2007 and 2017 GMHS. CS rates were compared between women with stillbirths and very early neonatal deaths (SBVENDs) and women with live births who survived the first day. Bivariate and multivariable logistic regressions explored variables associated with CS. Effect modification of household's wealth and maternal educational level by birth outcome was assessed using multivariable logistic regression with interaction terms. Results CS rate in women with SBVEND was 19.3% compared with 9.6% in women with live births who survived the first day (rate ratio 2.2; 95% CI 1.6 to 2.9). In multivariable analysis, attaining middle school compared with no formal education (adjusted OR, aOR 2.8; 95% CI 1.1 to 7.1), having had five or more births compared with nulliparity (aOR 3.7; 95% CI 1.3 to 10.7) and reporting prolonged or obstructed labour (aOR 3.3; 95% CI 1.3 to 8.3) were associated with CS in women with SBVEND. Higher household wealth and educational levels were associated with an increased risk of CS in both study groups, with no statistically significant difference in effect. Conclusion Disaggregating CS rates by birth outcome revealed a high rate among women with SBVEND, twice the overall rate compared with live births. Exclusion of these 'hidden' CSs from rate calculations may lead to underestimation of (inter)national CS rates and potentially conceals CS overuse or misuse.

Additional file 1: Table S1. Grey literature data sources and key findings for injury morbidity and mortality in India. Table S2. National and international data sources of injury morbidity and mortality in India rated according to attributes of injury surveillance. Supplementary Table 3. Status of WHO core and optional variables collected at data sources. Adapted WHO injury surveillance evaluation tool.

The limited availability and low-quality of national-level data to understand stillbirth determinants in low- and middle-income countries is a major barrier to stillbirth prevention efforts globally. Data for producing stillbirth estimates in these settings generally come from national household surveys due to the high proportion of women that give birth at home, and because of inadequate or absent civil and vital registration systems. There are several quality concerns with stillbirth data from household surveys, particularly around under-reporting and misclassification, which affect the reliability of estimates. What also remains underexplored is to what extent social and cultural factors affect the disclosure and reporting of stillbirth, as these have important implications for stillbirth data quality. This thesis sought to review the availability of country-level data on stillbirth from nationally-representative household surveys in low- and middle-income countries to outline what data exists, where the limitations are, and potential for improvement. Analysis of data from a national mortality survey in Afghanistan is used to describe the key determinants of stillbirth in this setting and demonstrate how better data could be generated to understand stillbirth risk factors globally. Qualitative methods are used to further explore how community and healthcare provider experiences, perceptions and practices might impact stillbirth data quality and contribute to pathways leading to stillbirth in Afghanistan. The findings of this thesis can inform future efforts to improve stillbirth data in low- and middle-income countries and identifies where interventions can begin to focus to facilitate stillbirth reduction in Afghanistan.

Background & Aims Aberrant DNA methylation is a common early event in neoplasia, but it is unclear how this relates to dysregulation of DNA (cytosine-5) methyltransferases (Dnmts). Here we use knock-in transgenic mice to investigate the consequences of intestinal epithelium-specific overexpression of de novo Dnmt3a. Methods A novel gene targeting strategy, based on the intestinal epithelium-specific, uniform expression of the A33 glycoprotein, is employed to restrict Dnmt3a overexpression in homozygous A33 Dnmt3a mutant mice. Results A33 Dnmt3a mice infrequently develop spontaneous intestinal polyps. However, when genetically challenged, tumor multiplicity in A33 Dnmt3a ; Apc Min compound mice is 3-fold higher than in Apc Min mice. Although we observe a requirement for spontaneous loss of heterozygosity of the adenomatous polyposis coli ( Apc ) gene to trigger tumorigenesis in Apc Min mice, lesions in A33 Dnmt3a ; Apc Min mice frequently retain the wild-type Apc allele. However, epithelia from normal mucosa and polyps of A33 Dnmt3a ; Apc Min mice show hypermethylation-mediated transcriptional silencing of the Wnt antagonists Sfrp5 , and to a lesser extent, Sfrp1 and increased nuclear β-catenin alongside activation of the Wnt-target gene Axin2/Conductin . Conversely, enforced Sfrp5 expression suppresses canonical Wnt-signaling more effectively in wild-type than in Apc Min cells. Conclusions Aberrant activation of the canonical Wnt pathway, either by mono-allelic Apc loss or transcriptional silencing of Sfrp5 is largely insufficient to promote polyposis, but epistatic interactions between these genetic and epigenetic events enables initiation and promotion of disease. This mechanism is likely to play a role in human colorectal cancer, because we also show that elevated DNMT3A expression coincides with repressed SFRP5 and enhanced AXIN2/CONDUCTIN expression in paired patient biopsies.