Oral and craniofacial research in the Generation R study: an executive summary.

OBJECTIVES: Oral conditions are of high prevalence and chronic character within the general population. Identifying the risk factors and determinants of oral disease is important, not only to reduce the burden of oral diseases, but also to improve (equal access to) oral health care systems, and to develop effective oral health promotion programs. Longitudinal population-based (birth-)cohort studies are very suitable to study risk factors on common oral diseases and have the potential to emphasize the importance of a healthy start for oral health. In this paper, we provide an overview of the comprehensive oral and craniofacial dataset that has been collected in the Generation R study: a population-based prospective birth cohort in the Netherlands that was designed to identify causes of health from fetal life until adulthood. METHODS: Within the multidisciplinary context of the Generation R study, oral and craniofacial data has been collected from the age of 3 years onwards, and continued at the age of six, nine, and thirteen. Data collection is continuing in 17-year-old participants. RESEARCH OUTCOMES: In total, the cohort population comprised 9749 children at birth, and 7405 eligible participants at the age of seventeen. Based on questionnaires, the dataset contains information on oral hygiene, dental visits, oral habits, oral health-related quality of life, orthodontic treatment, and obstructive sleep apnea. Based on direct measurements, the dataset contains information on dental caries, developmental defects of enamel, objective orthodontic treatment need, dental development, craniofacial characteristics, mandibular cortical thickness, and 3D facial measurements. CONCLUSIONS: Several research lines have been set up using the oral and craniofacial data linked with the extensive data collection that exists within the Generation R study. CLINICAL RELEVANCE: Being embedded in a multidisciplinary and longitudinal birth cohort study allows researchers to study several determinants of oral and craniofacial health, and to provide answers and insight into unknown etiologies and oral health problems in the general population.

Outcomes of dental implants in young patients with congenital versus non-congenital missing teeth.

OBJECTIVE: This cross-sectional study aims to investigate the effect of the cause of missing teeth on the survival and subjective success of dental implant treatment (DIT) in young patients with missing teeth due to non-congenital causes (tooth loss) in comparison to patients with missing teeth because of congenital causes (hypodontia and oligodontia). MATERIAL AND METHODS: All patients were asked 7 questions to extract information about the survival and subjective success of DIT. Implant survival function was designed using the Kaplan-Meier analysis. Differences in implant success outcomes were studied using binary logistic regression analysis. RESULTS: One hundred ten patients aged 18 to 40 years old were included, whereof 32 patients with tooth loss, 25 patients with hypodontia and 53 patients with oligodontia. In the tooth loss group, implant survival reached 96.9%; in the hypodontia group 96.0%; and in the oligodontia group 88.7%. Regarding subjective implant success, patient satisfaction was significantly higher (p < 0.040) among patients with congenital missing teeth in comparison to patients with tooth loss. Other implant success components showed no statistically significant difference (p > 0.050) between the groups. CONCLUSION: The cause of missing teeth does not influence implant survival. However, the cause of missing teeth does have a significant impact on patient satisfaction (implant success), ascertaining young patients with congenital missing teeth as more satisfied of DIT than young patients with tooth loss. CLINICAL RELEVANCE: Young patients with tooth agenesis and with an increased number of missing teeth are more content about the treatment with dental implants than patients with tooth loss. Furthermore, a consensus regarding the assessment of implant success is an essential concern for clarification.

The association of maternal folic acid supplementation and prenatal folate and vitamin B12 concentrations with child dental development.

OBJECTIVE: Low folic acid, folate and vitamin B12 might affect tooth formation and mineralization. The conversion of folic acid into folate is catalysed by the methylenetetrahydrofolate (MTHFR) enzyme which is encoded by the MTHFR gene. Among 3728 mothers and their 10-year-old children from the Generation R Study, we investigated associations of maternal folic acid supplementation and prenatal folate and vitamin B12 concentrations with child dental development. Secondly, we checked the modifying effect of MTHFR-C677T polymorphism. METHODS: Information on folic acid supplementation was obtained by questionnaires. Concentrations of folate and vitamin B12 were measured from venous samples taken in early pregnancy. Developmental stages of teeth were defined by the Demirjian method at the age-10 assessment. In addition, dental age of the children was calculated using the Dutch standard. GLM and multivariate linear regression models were built to study the associations. RESULTS: Folic acid supplementation started when pregnancy was known (ß = -0.09; 95% CI: -0.17, -0.01) and folic acid supplementation started prior to known pregnancy (ß = -0.12; 95% CI: -0.20, -0.04) were both associated with decelerated dental development by 1-2 months lower dental age of 10-year-old children. Folate (ß = -0.02, 95% CI: -0.05, 0.02) and vitamin B12 (ß = 0.03, 95% CI: -0.00, 0.06) were not associated with dental age. MTHFR-C677T did not modify the associations. CONCLUSIONS: Maternal folic acid supplementation delays dental development of children by 1-2 months dental age, whereas maternal folate and vitamin B12 concentrations in early pregnancy do not affect the timing of child dental development.

Effectiveness of the new mandatory mouthguard use and orodental injuries in Dutch field hockey.

ObjectivesUp to 68% of field hockey players have experienced at least one orodental injury in their sport career. Therefore, the Royal Dutch Hockey Association (KNHB) made mouthguard use mandatory for field hockey players during competition and training from August 2015 onwards.This study evaluates the effects of the new regulations on mouthguard use and the occurrence of injuries in Dutch field hockey.MethodsA 35-item online questionnaire about mouthguard use and orodental injuries was sent to 13 field hockey clubs in the Netherlands. Absolute numbers and percentages of mouthguard ownership, mouthguard use, number and type of injuries were assessed. The results were related to comparable data before mandatory mouthguard use. Associations of gender and training frequency with the number of injuries were analysed with logistic regression.ResultsIn total, 1169 hockey players were included in the study and almost all owned a mouthguard (females:99.6%, males:93.7%), which significantly increased after implementation (p < 0.001). 90.6% of the respondents wore a mouthguard during matches and 70.1% during training. Of the 1169 players, 68(5.8%) experienced at least one orodental injury after the implementation with a total of 100 injuries. Injuries happened more often during matches (63.2%) than during training (36.8%). Lip cuts account for most of the injuries, the number of broken (p = 0.116) and knocked out teeth (p = 0.026) decreased.ConclusionAlthough mouthguard use already increased in recent years, the new regulations led to an additional increase and a successful change of attitude towards mouthguard use. Most importantly, the severity of orodental injuries decreased measurable.

Skeletal maturation in relation to ethnic background in children of school age: The Generation R Study.

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 component.

Dental development and craniofacial morphology in school-age children.

INTRODUCTION: The growth of the craniofacial complex is important for establishing a balanced relationship among the teeth, jaws, and other facial structures. However, there is still a lack of information about craniofacial parameters that are affected by the rate of dental development. The aim of this study was to investigate the association between dental development and craniofacial morphology in school-age children. METHODS: This study was embedded in the Generation R Study, Rotterdam, The Netherlands. In 3,896 children aged 8 to 11 years, dental development was assessed from panoramic radiographs and craniofacial morphology was assessed by combining cephalometric parameters into 9 uncorrelated principal components, each representing a distinct skeletal or dental craniofacial pattern. The statistical analysis was performed using linear and nonlinear regression model. RESULTS: Dental development was positively associated with the bimaxillary growth (ß = 0.04; 95% CI 0.01 to 0.08). Children with above-average dental development had a tendency toward Class II jaw relationship (ß = -0.08; 95% CI -0.13 to -0.04). Regarding dental parameters, the proclination increased for incisors and lips with advanced dental development (ß = 0.15 [95% CI 0.10 to 0.19] and ß = 0.13 [95% CI 0.09 to 0.17], respectively), but the incisor proclination remained more pronounced in children that had above-average dental development. CONCLUSIONS: The findings of this large population-based study show that dental development is associated with specific dental and skeletal cephalometric characteristics in school-age children. Further longitudinal studies are necessary to confirm the observed effects over time.

The Associations of Maternal and Neonatal Vitamin D with Dental Development in Childhood.

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 concentrations of 25-hydroxyvitamin D [25(OH)D] during midpregnancy (ß: -0.04; 95% CI: -0.08, -0.01) and at birth (ß: -0.06; 95% CI: -0.10, -0.02) were associated with a lower dental age in children. The children of mothers with severe vitamin D deficiency [25(OH)D <25.0 nmol/L] during midpregnancy exhibited a higher dental age (ß: 0.14; 95% CI: 0.03, 0.24) and higher developmental stages of the mandibular first premolar (ß: 0.32; 95% CI: 0.04, 0.60) compared with the children of mothers with optimal values of 25(OH)D (≥75.0 nmol/L). Children with vitamin D deficiency [25(OH)D 25.0-49.9 nmol/L] at birth exhibited a higher dental age (ß: 0.11; 95% CI: 0.01, 0.20), higher developmental stages of the mandibular second premolar (ß: 0.27; 95% CI: 0.02, 0.51), and higher developmental stages of the mandibular second molar (ß: 0.24; 95% CI: 0.00, 0.48) compared with children with sufficient-to-optimal values of 25(OH)D (≥50.0 nmol/L) at birth. CONCLUSION: Higher maternal and neonatal 25(OH)D concentrations are associated with decelerated dental development in childhood. The lower the vitamin D level during midpregnancy or at birth, the higher the dental age of children, and the higher the developmental stages of the mandibular teeth.

The role of accelerated dental development on the occurrence of aberrant dental traits that indicate malocclusion.

BACKGROUND: Timing of dental development might help orthodontists to optimize initiation of treatment and to prevent and intercept dental misalignment. This study examines the association between timing of dental development and aberrant dental traits such as crowding, impaction, and hypodontia. METHODS: This study was performed using 4446 ten-year-old children from a multiethnic birth cohort, the Generation R Study. Dental development was defined using the Demirjian method. Crowding, impaction, and hypodontia were ascertained from 2D and 3D pictures and radiographs. We built three series of logistic regression models to test the associations of dental age with crowding, impaction, and hypodontia. Similar models were built to investigate the associations of the developmental stages of each left mandibular tooth with crowding, impaction, and hypodontia. RESULTS: Inverse associations were found between every 1-year increase in dental age and the presence of crowding [odds ratio (OR) = 0.84, 95% confidence interval (CI): 0.79, 0.89], impaction of teeth (OR = 0.66, 95% CI: 0.52, 0.84), and hypodontia (OR = 0.52, 95% CI: 0.47, 0.56). Lower developmental stages of the second premolar were associated with the presence of crowding (OR = 0.90, 95% CI: 0.83, 0.98). Lower developmental stages of the second premolar (OR = 0.88, 95% CI: 0.79, 0.98), first molar (OR = 0.76, 95% CI: 0.65, 0.90), and the second molar (OR = 0.83, 95% CI: 0.73, 0.94) were associated with the presence of tooth impaction. Lower developmental stages of all mandibular teeth except the central incisor were associated with hypodontia (P < 0.05). CONCLUSION: Accelerated dental development is associated with lower occurrence of crowding, impaction, and hypodontia.

Does dental caries affect dental development in children and adolescents?

Although a link between dietary changes, caries, and dental development has been observed, the literature provides little insight about this relationship. The aim of our study was to investigate the association between dental caries and dental development in a clinical sample of Albanian children and adolescents. In total, 118 children and adolescents, born between 1995 and 2004 and aged 6-15 years, were included. Dental caries in the deciduous dentition was assessed using the Decayed, Filled Teeth (dft) index and dental caries in the permanent dentition was assessed using the Decayed, Missing, Filled Teeth (DMFT) index. Dental development during the permanent dentition was determined using the Demirjian method. Linear and ordinal regression models were applied to analyze the associations of dental caries with dental age and developmental stages of each left mandibular tooth. Dental caries in the deciduous dentition, estimated as a median dft of 2.0 (90% range, 0.0-9.1), was significantly associated with lower dental age (ß = -0.21; 90% CI: -0.29, -0.12) and with delayed development of the canine, both premolars, and the second molar. Untreated dental caries (dt) was associated with lower dental age (ß = -0.19; 90% CI: -0.28, -0.10). Dental caries in the permanent dentition, estimated as a median DMFT of 1.0 (90% range, 0.0-8.0), was not significantly associated with dental age (ß = 0.05; 90% CI: -0.04, 0.14). However, the DMFT was associated with the advanced stages of development of both premolars and the second molar. The untreated dental caries in the deciduous dentition delays the development of permanent teeth.

Ancestry and dental development: A geographic and genetic perspective.

OBJECTIVE: In this study, we investigated the influence of ancestry on dental development in the Generation R Study. METHODS: Information on geographic ancestry was available in 3,600 children (1,810 boys and 1,790 girls, mean age 9.81 ± 0.35 years) and information about genetic ancestry was available in 2,786 children (1,387 boys and 1,399 girls, mean age 9.82 ± 0.34 years). Dental development was assessed in all children using the Demirjian method. The associations of geographic ancestry (Cape Verdean, Moroccan, Turkish, Dutch Antillean, Surinamese Creole and Surinamese Hindustani vs Dutch as the reference group) and genetic content of ancestry (European, African or Asian) with dental development was analyzed using linear regression models. RESULTS: In a geographic perspective of ancestry, Moroccan (ß = 0.18; 95% CI: 0.07, 0.28), Turkish (ß = 0.22; 95% CI: 0.12, 0.32), Dutch Antillean (ß = 0.27; 95% CI: 0.12, 0.41), and Surinamese Creole (ß = 0.16; 95% CI: 0.03, 0.30) preceded Dutch children in dental development. Moreover, in a genetic perspective of ancestry, a higher proportion of European ancestry was associated with decelerated dental development (ß = -0.32; 95% CI: -.44, -.20). In contrast, a higher proportion of African ancestry (ß = 0.29; 95% CI: 0.16, 0.43) and a higher proportion of Asian ancestry (ß = 0.28; 95% CI: 0.09, 0.48) were associated with accelerated dental development. When investigating only European children, these effect estimates increased to twice as large in absolute value. CONCLUSION: Based on a geographic and genetic perspective, differences in dental development exist in a population of heterogeneous ancestry and should be considered when describing the physiological growth in children.

Craniofacial characteristics of children with mild hypodontia.

INTRODUCTION: The aim of our study was to evaluate the craniofacial characteristics of children with mild hypodontia using conventional and principal component (PC) analysis. METHODS: We used radiographic images of 124 children (8-12 years old) with up to 4 missing teeth (55 boys, 69 girls) and of 676 reference children (365 boys, 311 girls) from the Rotterdam Generation R Study and the Nijmegen Growth Study in The Netherlands. Fifteen cephalometric measurements of children with hypodontia were compared with those of the reference children. Moreover, cephalometric parameters were combined into standardized PC scores using PC analysis, and the components were compared between the 2 groups. RESULTS: PC analysis showed common dental characteristics for all types of hypodontia: a significant increase of the interincisal angle, and decreases of the maxillary and mandibular incisor angles. Other findings were consistent when both methods were applied: (1) anterior hypodontia was significantly associated with the high-angle (hyperdivergent) craniofacial pattern, (2) the tendency toward a Class III malocclusion was identified in maxillary hypodontia, and (3) we observed a significant reduction of lower posterior facial height in children with posterior and mandibular hypodontia. CONCLUSIONS: Our findings suggest that children with mild hypodontia have distinctive skeletal and dental features.

The association between WNT10A variants and dental development in patients with isolated oligodontia.

In this study we aimed to determine the effect of WNT10A variants on dental development in patients with oligodontia. Forty-three (25 boys and 18 girls) individuals were eligible for this study. Stage of development for each present tooth was assessed using the Demirjian method. In case no corresponding tooth was present, regression equations were applied for dental age to be calculated. The ratio between length of root and length of crown was ascertained for each present tooth in all quadrants. All patients were physically examined by a clinical geneticist and DNA analysis of the WNT10A gene was performed. Linear regression models were applied to analyze the association between WNT10A variants and dental age. The same analysis was applied to study the association between WNT10A variants and root elongation for each present tooth. One ordinal regression model was applied to analyze the association between WNT10A variants and development of present maxillary and mandibular teeth. Thirty-six (84%) patients were detected with WNT10A variants of which six patients displayed evident ectodermal features. Dental age was 1.50 (95% confidence interval (CI): -2.59, -0.42) to 1.96 (95% CI: -3.76, -0.17) years lower in patients with WNT10A variants compared with patients without variants. The development of maxillary canine, maxillary second molar and mandibular second molar was statistically significantly delayed in patients with WNT10A variants compared with patients without variants. The impact of WNT10A variants on dental development increases with presence of the nonsense c.(321C>A p.(C107*)) variant and the number of missing teeth.

The association between hypodontia and dental development.

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.

The impact of malocclusions on oral health-related quality of life in children-a systematic review and meta-analysis.

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.