Oral diseases affect 3.9 billion people worldwide, and dental caries is the most prevalent oral condition. Untreated caries in permanent and deciduous dentitions were reported among approximately 35% and 9% of the world population, respectively, in 2010. Moreover, it is the fourth-most expensive chronic disease to treat according to the World Health Organization. The importance of various social, environmental, familial, and behavioural factors on childhood caries has been identified by earlier researchers. In the past, epidemiological research on caries has mainly focused on describing biological and dietary determinants of the disease. During the past few decades, there has been an effort to explore children’s oral health outcomes using a broader framework, incorporating behavioural, social, and environmental predictors with biological and genetic factors. Despite the fact that these characteristics have been found to be significantly associated with childhood caries experience in different population groups, there has been scarce research exploring the whole range of putative risk factors, and their associated risk indicators, and their possible interactions, simultaneously, in a single child cohort. In particular, the impact of the epigenome and of the in utero environment on susceptibility to dental caries has not been reported in children from a typical Western industrialised country. Hence, this thesis explored a wide range of factors: environmental, socio-economic, behavioural, maternal (including throughout pregnancy), children’s individual factors (including well-established risks associated with diet and hygiene practices), and a screen for epigenetic modifications, as indicators of risk for childhood caries. Participants were 174, six- to seven-year-old children and their mothers from South East Queensland, who were originally enrolled in the Environments for Healthy Living (EFHL) Griffith University birth cohort study. Participants for the oral health sub-study were volunteers obtained from the EFHL database who were willing to come for an oral examination at Griffith dental clinics. Mothers completed a questionnaire on oral health knowledge and behaviours at the dental clinic followed by anthropometric measurements. Trained and calibrated examiners conducted detailed head and neck, and oral examinations, and recorded participant’s salivary characteristics and dental caries scores. Total DNA was extracted from each participant’s saliva for sequencing and methylation arrays to detect epigenetic changes. Descriptive statistics, negative binomial regression, and path analyses were performed to evaluate the associations between risk indicators and the lifetime dental caries experience of each child. Maternal risk indicators included mother’s age at examination, her lifetime caries experience, oral health knowledge and practices, body mass index, saliva characteristics of clinical oral hydration, stimulated flow rate, pH, buffering capacity, and load of salivary mutans Streptococci and Lactobacilli. Results indicated that low annual household income was a risk indicator for dental caries experience in this child population. Maternal behaviours: initiating child’s tooth brushing later than six months of age and a high frequency of giving carbonated drinks to the child were associated with increased caries experience in their children. In addition, high loads of maternal oral Lactobacilli were related to the children’s increased risk of caries. Moreover, children’s past caries experience, and increased levels of salivary mutans Streptococci were recognised to be significant risk indicators for their dental caries experience. Children whose mothers took iron supplements during pregnancy had low levels of caries (past and current) compared to their counterparts. One highlight of the thesis has been the cutting-edge evidence of an association between epigenetic modifications and caries experience of individuals. There were significant differences in differentially methylated regions between persons with high and low caries experience on chromosomes 1, 2, 5, 7, 12, 20 and 22. Chromosome 12, in particular, showed the highest average methylation difference between the two groups. Further, functional annotations of related genes revealed that there are two gene clusters related to zinc (Zn) metabolism and membrane protein functions, which could indirectly be related to the caries process. In summary, the study found maternal, environmental, and children’s characteristics that were risk indicators for caries experience in this child population. It was observed that low maternal income and poor oral health behaviours had positive associations with children’s caries experience. Also, bad oral health of the mother, expressed as maternal caries experience, placed their children at risk of dental caries. Similarly, children with poor oral health with past caries and high counts of cariogenic bacteria, along with reported low maternal iron supplements during pregnancy were more at risk of continuing to develop dental caries than their counterparts. The latter could reflect inadequate iron during pregnancy and consequent sub-optimal development of foetal tissues and immune responses. The pilot study of 12 mother child dyads to explore associations between epigenetic changes and lifetime caries experience suggests that epigenetic modifications might, indeed, predispose individuals to dental caries. However, with such a small sample size, this cannot be a firm conclusion. Nevertheless it leads to the generation of hypotheses which can be tested in further studies.” This thesis adds new knowledge to the current literature on local, systemic and environmental factors influencing susceptibility and resistance to the process of childhood caries. The results also offer new avenues for health promotion using a common risk factor approach to improve maternal behaviours and nutrition, which would eventually enhance the clinical caries outcomes in children.