tion (MIH), and dental caries. Children affected by HSPM and/or MIH have brittle dental enamel due to less mineralization, which may result in a higher caries susceptibility or even early tooth loss. Somewhere in the complex process of tooth development, the cells involved with enamel mineralization show problems to facilitate mineralization of the extracellular matrix. Factors causing these problems, however, are largely unknown. It is speculated that early childhood diseases may cause these mineralization issues, but the exact etiology of HSPM and MIH is still unknown. On the contrary, the etiology of dental caries has been well established. Dental caries is a multifactorial disease. Major risk factors are a low frequency of fluoride use and a high frequency of sugar intake. Preventive strategies focus most on those two risk factors and are quite successful. Yet, it is expected that the caries prevalence in children can reach even lower numbers. Identification of risk groups and/or new risk factors may help to develop more effective caries prevention strategies. Aims of this thesis were to further explore the etiology of dental enamel hypomineralization, to identify major risk groups and risk factors for dental caries, and to assess the use of relatively new instrument, a Quantitatve Light induced Fluorescent (QLF)-camera, for diagnosing dental enamel hypomineralization and dental caries within an epidemiological study setting. All studies, except the last study, were embedded within a population-based cohort study following children from fetal life until adulthood, the Generation R Study. Dental enamel hypomineralization and dental caries were assessed at the children’s age of six from intra-oral photographs. In Chapter 2 we tried to further unravel the etiology of dental enamel hypominer- alization. First, we assessed the association between the children’s bone mass and dental enamel hypomineralization. Since the same minerals play a crucial role in both bone development and enamel maturation, we hypothesized that children’s bone mass could be an indicative factor for having dental enamel hypomineralization. Bone mass was measured using a Dual-energy X-ray Absorptiometry scan at the age of six (DXA-scan). Eventually, we found a low child’s bone mineral content (BMC) to be associated with a higher presence of HSPM. No significant association was found between BMC and MIH. Furthermore, in the search for etiologic factors of dental enamel hypomineralization, we assessed the association between vitamin D status and HSPM/MIH. Vitamin D is an important mediator in bone metabolism, vitamin D receptors are found on ameloblasts, and may therefore (partly) explain the found association between a child’s BMC and the presence of HSPM. We measured vitamin D serum concentrations at three points in time; mid-gestational from the mother’s blood sample, early postnatal from umbilical
cord blood, and at the age of six from the child’s blood sample. After analyzing the results, however, the vitamin D serum concentrations were neither associated with the presence of HSPM at the age of six, nor with MIH. Based on our findings, we were not able to identify a new risk factor for dental enamel hypomineralization nor to explain the found association between a child’s bone mass and the presence of HSPM in children.
In Chapter 3 we focused on dental caries. First, we explored the presence of ethnic disparities in dental caries among the children from the Generation R Study, independent of SEP. For this study we distinguished seven different ethnic groups, including the most important ethnic minority groups within the Netherlands: Dutch, Surinamese-Hindustani, Surinamese-Creole, Turkish, Dutch Antillean, Moroccan, and Cape Verdean. Compared to native Dutch children, children with a Surinamese- Hindustani, Surinamese-Creoles, Turkish, Moroccan, and Cape Verdean background had significantly higher odds for dental caries. Especially the Surinamese-Hindustani, Turkish, and Moroccan group had significantly higher odds for severe dental caries (more than three teeth affected by decay, missing teeth and/or filings due to caries). Household income and educational level of the mother explained up to 43% of the association between ethnicity and dental caries. Public health strategies can apply this new knowledge and specifically focus on the reduction of ethnic disparities in oral health.
Second, we assessed whether dental caries traits in children and adolescents are partially heritable. For this purpose, we performed a genome-wide association study (GWAS) within an international consortium of nine different cohort studies with participants aged from 2.5 up to 18.0 years. Phenotype definitions were created for the presence or absence of treated or untreated caries, stratified by primary and permanent dentition. Analysis included up to 19,003 individuals (7,530 affected) for primary teeth and 13,353 individuals (5,875 affected) for permanent teeth. Eventually, we found two different single variants to be associated with dental caries in the pri- mary and permanent dentition (rs1594318-C and rs7738851-A, respectively). However, consortium-wide estimated heritability of caries was low compared to corresponding within-study estimates or previously published estimates. Phenotypic heterogene- ity between cohorts and limited statistical power might have contributed to the low number of found single variants and the relatively low heritability. These findings could also reflect complexity not captured by our study design, such as genetic effects which are conditional on environmental exposure.
Third, we explored social inequalities in dental caries prevalence among six-year- old children from the Generation R Study. We did this by assessing the association between seven different indicators for socioeconomic position (SEP) and by using a