Generation R
The Generation R Study is a prospective cohort study from foetal life until young adulthood in a multi-ethnic urban population. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health from foetal life until young adulthood. Eventually, results forthcoming from the Generation R Study have to contribute to the development of strategies for optimizing health and healthcare for pregnant women and children.
On the spring 2017 Generation R launched a new cohort study: Generation R Next. An important aim of Generation R Next is to study the health and lifestyle of a mother-to-be before pregnancy and the effects on the growth and development of her child.
Both studies focus on five primary areas of research:
- Growth and physical development
- Behavioral and cognitive development
- Asthma and atopy
- Diseases in childhood
- Health and healthcare
Our contribution to the Generation R study
Within the Generation R Study, our group has actively work on the generation of the genetic data and a periodical update of the algorithms to exploit the complex nature of this multhiethnic cohort. Besides multi-ethnic research, approaches as admixture mapping, trio-design, genetic nurture and exploration of evolutive pressures.
In addition, our group is leading the research in musculoskeletal traits in children. Musculoskeletal homeostasis during childhood has a complex and dynamic etiology influenced by environmental and genetic factors. The Generation R Study has a broad range of musculoskeletal phenotypes acquired from participants from a mean age of 6 years to 17 years old. These include, DXA, pQCT, mecanograph and handgrip measurements.
Publications
Oral and craniofacial research in the Generation R study: an executive summary
Oral and craniofacial research in the Generation R study: an executive summary
Abstract
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.
Keywords:Cohort studies; Dental health; Dental public health; Epidemiology; Population-based.
For more information on this article in Pure, click here.
Bone health index in the assessment of bone health: The Generation R Study
Bone health index in the assessment of bone health: The Generation R Study
Abstract
Bone Health Index (BHI) has been proposed as a useful instrument for assessing bone health in children. However, its relationship with fracture risk remains unknown. We aimed to investigate whether BHI is associated with bone mineral density (BMD) and prevalent fracture odds in children from the Generation R Study. We also implemented genome-wide association study (GWAS) and polygenic score (PGS) approaches to improve our understanding of BHI and its potential. In total, 4150 children (49.4 % boys; aged 9.8 years) with genotyped data and bone assessments were included in this study. BMD was measured across the total body (less head following ISCD guidelines) using a GE-Lunar iDXA densitometer; and BHI was determined from the hand DXA scans using BoneXpert®. Fractures were self-reported collected with home questionnaires. The association of BHI with BMD and fractures was evaluated using linear models corrected for age, sex, ethnicity, height, and weight. We observed a positive correlation between BHI and BMD (ρ = 0.32, p-value<0.0001). Further, every SD decrease in BHI was associated with an 11 % increased risk of prevalent fractures (OR:1.11, 95 % CI 1.00-1.24, p-value = 0.05). Our BHI GWAS identified variants (lead SNP rs1404264-A, p-value = 2.61 × 10-14) mapping to the ING3/CPED1/WNT16 locus. Children in the extreme tails of the BMD PGS presented a difference in BHI values of -0.10 standard deviations (95% CI -0.14 to -0.07; p-value<0.0001). On top of the demonstrated epidemiological association of BHI with both BMD and fracture risk, our results reveal a partially shared biological background between BHI and BMD. These findings highlight the potential value of using BHI to screen children at risk of fracture.
Keywords: BMD; Bone fracture; Bone health index; GWAS; Pediatric cohort; Recall-by-genotype.
For more information on this article in Pure, click here.
Associations of fetal and infant growth with pubertal timing
Associations of fetal and infant growth with pubertal timing
Abstract
Objective: Impaired fetal and infant growth may cause alterations in developmental programming of the hypothalamic-pituitary-gonadal axis and subsequently pubertal development. We aimed to assess associations between fetal and infant growth and pubertal development.
Design: Population-based prospective birth cohort.
Setting: Rotterdam, the Netherlands.
Patients: 5830 singleton born children.
Interventions: We estimated fetal weight in second and third trimester by ultrasound. Infant growth measures were gestational age and weight at birth and infant weight at 6, 12 and 24 months.
Main outcome measures: Pubertal timing outcomes included difference between chronological and skeletal age assessed using dual-energy X-ray absorptiometry, testicular or ovarian volumes assessed using MRI at 10 years, age at menarche and Tanner staging at 13 years.
Results: Among girls, 1-SD scores birth weight increase was associated with larger ovarian volume at 10 years (0.07 SD (95% CI 0.02 to 0.12) and later age at menarche (0.06 (0.02 to 0.11)). Among girls, increased infant growth was associated with an older skeletal age at 10 years (difference 2.67 (95% CI 2.26 to 3.08) months), earlier menarche (difference 0.10 (95% CI -0.14 to -0.06) years) and more advance breast and pubic hair development at 13 years (difference in Tanner stages 0.09 (0.05 to 0.13) and 0.07 (0.03 to 0.12)). In boys, increased infant growth was associated with an older skeletal age (3.13 (95% CI 2.58 to 3.69) months) and a larger testicular volume (0.07 (95% 0.02 to 0.12) SD) at 10 years, and with more advance pubic hair development (0.09 (95% CI 0.05 to 0.14) at 13 years).
Conclusion: Birth anthropometrics and early-life growth patterns are associated with altered pubertal development in a sex-specific manner.
Keywords: Endocrinology; Growth; Infant Development.
For more information on this article in Pure, click here.
Associations between Prenatal, Perinatal, and Early Childhood Vitamin D Status and Risk of Dental Caries at 6 Years
Associations between Prenatal, Perinatal, and Early Childhood Vitamin D Status and Risk of Dental Caries at 6 Years
- DOI: 10.1093/jn/nxab075
Abstract
Background: Previous studies have suggested that insufficient concentrations of vitamin D are associated with dental caries in primary teeth, but evidence remains inconclusive.
Objectives: We assessed the longitudinal associations between prenatal, perinatal, and early childhood serum 25-hydroxyvitamin D concentrations [25(OH)D] and the risk of dental caries in 6-year-old children.
Methods: This research was conducted within the Generation R Study, a large, multi-ethnic, prospective cohort study located in Rotterdam, the Netherlands. Dental caries were assessed in children using the decayed-missing-filled-primary teeth index at a mean age of 6.1 years (90% range, 4.8-9.1). We measured serum total 25(OH)D concentrations at 3 time points: prenatally (at 18-24 weeks of gestation), perinatally (at birth), and during early childhood (at age 6 years). We performed logistic regression analyses to determine the longitudinal association of serum 25(OH)D concentrations with caries risks in 5257 children. Additionally, we constructed a Genetic Risk Score (GRS) for the genetic predispositions to serum total 25(OH)D concentrations based on 6 vitamin D-related single nucleotide polymorphisms in a subsample of 3385 children.
Results: Children with severe prenatal and early childhood serum 25(OH)D deficiencies (<25 nmol/L) were more likely to be diagnosed with caries [OR, 1.56 (95% CI, 1.18-2.06) and 1.58 (95% CI, 1.10-2.25), respectively] than children with optimal concentrations (≥75 nmol/L). After adjustment for residuals of serum 25(OH)D concentrations at other time points, only the early childhood serum 25(OH)D concentration was inversely associated with the caries risk at 6 years (OR, 0.97; 95% CI, 0.95-0.98). However, our GRS analysis showed that children who are genetically predisposed to have lower serum 25(OH)D concentrations do not have a higher risk of developing caries in primary teeth.
Conclusions: Our study suggests a weak association between serum 25(OH)D concentrations and risks of caries in primary teeth. Based on our results, we do not recommend vitamin D supplementation for the prevention of dental caries in children.
Keywords: 25(OH)D; caries; genetic risk score; pediatric dentistry; prevention; primary teeth.
For more information on this article in Pure, click here.
Oral microbiota of adolescents with dental caries: A systematic review
Oral microbiota of adolescents with dental caries: A systematic review
Abstract
Objective: This systematic review summarizes the current knowledge on the association between the oral microbiota and dental caries in adolescents.
Design: An electronic search was carried out across five databases. Studies were included if they conducted research on generally healthy adolescents, applied molecular-based microbiological analyses and assessed caries status. Data extraction was performed by two reviewers and the Newcastle-Ottawa Scale was applied for quality assessment.
Results: In total, 3935 records were reviewed which resulted in a selection of 20 cross-sectional studies (published 2005-2022) with a sample size ranging from 11 to 614 participants including adolescents between 11 and 19 years. The studies analyzed saliva, dental biofilm or tongue swabs with Checkerboard DNA-DNA hybridization, (q)PCR or Next-Generation Sequencing methods. Prevotella denticola, Scardoviae Wiggsiae, Streptococcus sobrinus and Streptococcus mutans were the most frequently reported species presenting higher abundance in adolescents with caries. The majority of the studies reported that the microbial diversity was similar between participants with and without dental caries.
Conclusion: This systematic review is the first that shows how the oral microbiota composition in adolescents appears to differ between those with and without dental caries, suggesting certain taxa may be associated with increased caries risk. However, there is a need to replicate and expand these findings in larger, longitudinal studies that also focus on caries severity and take adolescent-specific factors into account.
Keywords: Bacteria; Growth/Development; Microbiome; Risk facor(s); Streptococcus mutans.
For more information on this article in Pure, click here.
Protein intake during pregnancy and offspring body composition at 6 years: the Generation R Study
Protein intake during pregnancy and offspring body composition at 6 years: the Generation R Study
Abstract
Purpose: Intra-uterine exposure to protein may affect body composition and may increase the prevalence of childhood adiposity. Therefore, we examined whether protein intake during pregnancy is associated with offspring body composition at the age of 6 years and whether associations differ for animal protein and vegetable protein.
Methods: We included 2694 Dutch mother-child pairs participating in a prospective population-based cohort in Rotterdam, the Netherlands. Energy-adjusted protein was measured in pregnancy using a food-frequency questionnaire and analyzed in quartiles. At a mean age of 6.1 ± 0.4 years, we measured children’s body mass index, and fat-free mass index and fat mass index using dual-energy X-ray absorptiometry. Outcomes were standardized for age and sex. BMI was used to classify children’s overweight status.
Results: After adjustment for sociodemographic and lifestyle factors, a higher maternal protein intake was associated with a higher children’s fat-free mass index [difference 0.14 standard deviation (95 % CI 0.03, 0.25) for highest vs. lowest quartile of protein intake], but not with children’s fat mass index or body mass index. Comparable associations were found for animal protein and vegetable protein. Maternal protein intake was not associated with children’s overweight.
Conclusions and relevance: This study suggests that higher protein intake during pregnancy is associated with a higher fat-free mass in children at the age of 6 years, but not with their fat mass. Our results do not suggest specific recommendations regarding maternal protein intake during pregnancy to prevent overweight in the offspring.
Keywords: Body composition; Fetal programming; Obesity; Offspring; Pregnancy; Protein intake.
For more information on this article in Pure, click here.
