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Ethnicity is a well-established determinant of pediatric maturity, but the underlying genetic and environmental contributions to these ethnic differences are poorly comprehended. We aimed to evaluate the influence of ethnicity on skeletal age (SA), an assessment of pediatric maturation widely used in clinical settings. We included children from the Generation R Study, a multiethnic population-based pregnancy cohort, assessed at a mean age of 9.78 (±0.33) years. SA was evaluated by a trained observer on hand DXA scans using the Greulich and Pyle method. Ethnic background was defined as geographic ancestry (questionnaire-based assessment) (N = 5325) and genetic ancestry (based on admixture analysis) (N = 3413). Associations between the ethnic background and SA were investigated separately in boys and girls, using linear regression models adjusted for age, height and BMI. Based on geographic ancestry, 84% of the children were classified as European, 6% as Asian and 10% as African. Children of European background had on average younger SA than those of Asian or African descent. Asian boys had 0.46 (95% CI 0.26–0.66, p-value < 0.0001) and African boys 0.36 years (95% CI 0.20–0.53, p-value < 0.0001) older SA as compared to European boys. Similarly, Asian girls showed 0.64 (95% CI 0.51–0.77, p-value < 0.0001) and African girls 0.38 years (95% CI 0.27–0.48, p-value < 0.0001) older SA as compared to European girls. A similar pattern was observed in the analysis with genetically-defined ancestry. Furthermore, an increase in the proportion of Asian or African component was associated with older SA in both boys (log[Non-European/European]proportion = 0.10, 95% CI 0.06–0.13, p-value < 0.0001) and girls (log[Non-European/European]proportion = 0.06, 95% CI 0.04–0.08, p-value < 0.0001). In summary, children of Asian and African backgrounds have on average older SA as compared to children of European descent, partially explained by a genetic comp

Background: Vitamin D influences the formation and mineralization of teeth. Objective: To investigate the association of maternal and neonatal vitamin D concentrations with the dental development of 10-y-old children, in a population-based prospective cohort study among 3,770 mothers and children in the Netherlands. Methods: Maternal venous blood samples were collected in the second trimester (median 20.4 weeks of gestation; range: 18.5-23.2 wk) whereas umbilical cord blood samples were collected immediately after delivery (median 40.1 weeks of gestation; range 35.9-42.3 wk). Dental development was defined using the Demirjian method. Multivariate regression models were built to analyze the studied associations. Results: High concent

We present association results from a large genome-wide association study of tooth agenesis (TA) as well as selective TA, including 1,944 subjects with congenitally missing teeth, excluding third molars, and 338,554 controls, all of European ancestry. We also tested the association of previously identified risk variants, for timing of tooth eruption and orofacial clefts, with TA. We report associations between TA and 9 novel risk variants. Five of these variants associate with selective TA, including a variant conferring risk of orofacial clefts. These results contribute to a deeper understanding of the genetic architecture of tooth development and disease. The few variants previously associated with TA were uncovered through candidate gene studies guided by mouse knockouts. Knowing the etiology and clinical features of TA is important for planning oral rehabilitation that often involves an interdisciplinary approach.

Dental development is defined as a progressive and continuous process determined by epithelial-mesenchymal interactions and controlled by genetic, epigenetic and environmental factors over time. In this thesis we built three main objectives. The _first objective_ was to assess whether early life determinants indicate variations of dental development in Childhood. The _second objective_ was to study the role of the most common dental related problems on the developing dentition. The _third objective_ was to examine the direct and indirect genetic implications in disturbed dental development. The manuscripts of this thesis are conducted in the general and clinical population. Data in the general population was collected from two cohorts, the Generation R Study and the Nijmegen Growth Study. To extend our research on disturbances of dental development, we collected data from three University Medical Centers and two private clinical centers. In this thesis we concluded that early life determinants including ancestral background and maternal nutritional biomarkers are associated with dental development in children and can explain normal variations in dental development. Furthermore, anomalies and diseases affecting teeth directly, such as hypodontia and caries, can lead to delayed dental development that can be clinically relevant. Lastly, genetic implication is crucial in explaining disturbances of dental development. The more severe the condition is displayed, the more distinctive the disturbances of dental development are revealed. The severity of these disturbances in patients with oligodontia is addressed to genetic dysfunction involving directly genes responsible for dental formation and/or genes responsible for ectoderm genesis.

Structured Abstract: Objective: To investigate phenotypic differences in dental development between isolated oligodontia and oligodontia-ectodermal dysplasia (ED). Setting and sample population: A total of 129 patients diagnosed with isolated oligodontia and 22 patients with oligodontia as part of ED were eligible. Methods: The phenotype of dental devel

Dental development is defined as a progressive and continuous process determined by epithelial-mesenchymal interactions and controlled by genetic, epigenetic and environmental factors over time. In this thesis we built three main objectives. The _first objective_ was to assess whether early life determinants indicate variations of dental development in Childhood. The _second objective_ was to study the role of the most common dental related problems on the developing dentition. The _third objective_ was to examine the direct and indirect genetic implications in disturbed dental development. The manuscripts of this thesis are conducted in the general and clinical population. Data in the general population was collected from two cohorts, the Generation R Study and the Nijmegen Growth Study. To extend our research on disturbances of dental development, we collected data from three University Medical Centers and two private clinical centers. In this thesis we concluded that early life determinants including ancestral background and maternal nutritional biomarkers are asso

Objectives: In this cross-sectional study, we aimed to investigate the pattern of hypodontia in the Dutch population and determine the association between hypodontia and dental development in children with and without hypodontia, applying three different standards, Dutch, French Canadian, and Belgian, to estimate dental age. Methods: We used dental panoramic radiographs (DPRs) of 1488 children (773 boys and 715 girls), with a mean age of 9.76 years (SD = 0.24) participating in a population-based cohort study in Rotterdam, the Netherlands, born in 2002–2004, and 452 children (219 boys and 233 girls) with a mean age of 9.83 years (SD = 1.09) participating in a mixed-longitudinal, interdisciplinary population-based cohort study in Nijmegen, the Netherlands born in 1960–1968. Results: The prevalence of hypodontia in the Generation R Study was 5.6 % (N = 84) and 5.1 % (N = 23) in the Nijmegen Growth Study. Linear regression analysis showed that children with hypodontia had a 0.37 [95 % CI (−0.53,-0.21)] to 0.52 [95 % CI (−0.76,-0.38)] years lower dental age than children without hypodontia. The ordinal regression analysis showed a delay in development of mandibular second premolars [1.68 years; 95 %CI (−1.90,-1.46)], mandibular first premolars [0.57 years; 95 % CI (−0.94,-0.20)], and mandibular second molars [0.47 years; 95 % CI (−0.84,-0.11)]. Conclusion: These findings suggest that children with hypodontia have a delayed dental development. Clinical relevance: The delay of dental development in children with hypodontia should be taken into consideration and therefore orthodontists should recognize that a later start of treatment in these patients may be necessary.

Introduction: A limited amount of systematic literature reviews on the association between malocclusions and oral health-related quality of life (OHRQOL) summarize inconclusive results. Therefore, we conduct a systematic review and meta-analysis on the association of malocclusions with OHRQOL in children. Methods: Relevant studies were identified in Pubmed, Embase, Cochrane, Google Scholar and other databases. All studies with data on malocclusions or orthodontic treatment need and OHRQOL in children were included. Methodological quality of the studies was assessed with the Newcastle-Ottawa Scale (NOS). Random effects models were used to estimate summary effect measures for the association between malocclusion and OHRQOL in a continuous and a categorical data analysis. Tests for heterogeneity, publication bias and sensitivity of results were performed. Results: In total, 40 cross-sectional studies were included in the meta-analyses. Summary measures of the continuous data show that OHRQOL was significantly lowered in children with malocclusions (standardized mean difference (95 % CI] = 0.29 (0.19–0.38)). The summary odds ratio for having an impact on OHRQOL was 1.74 times higher in children with malocclusion than in children without malocclusions. Heterogeneity among studies was partly explained by malocclusion assessment, age of the children and country of study conduction. Conclusion: Our results provide evidence for a clear inverse association of malocclusion with OHRQOL. We also showed that the strength of the association differed depending on the age of the children and their cultural environment. Clinical relevance: Dentists benefit from understanding the patient differences regarding the impact of malocclusions.