Media use trajectories and risk of metabolic syndrome in European children and adolescents: the IDEFICS/I.Family cohort.

BACKGROUND: Media use may influence metabolic syndrome (MetS) in children. Yet, longitudinal studies are scarce. This study aims to evaluate the longitudinal association of childhood digital media (DM) use trajectories with MetS and its components. METHODS: Children from Belgium, Cyprus, Estonia, Germany, Hungary, Italy, Spain and Sweden participating in the IDEFICS/I.Family cohort were examined at baseline (W1: 2007/2008) and then followed-up at two examination waves (W2: 2009/2010 and W3: 2013/2014). DM use (hours/day) was calculated as sum of television viewing, computer/game console and internet use. MetS z-score was calculated as sum of age- and sex-specific z-scores of four components: waist circumference, blood pressure, dyslipidemia (mean of triglycerides and HDL-cholesterol-1) and homeostasis model assessment for insulin resistance (HOMA-IR). Unfavorable monitoring levels of MetS and its components were identified (cut-off: ≥ 90th percentile of each score). Children aged 2-16 years with ≥ 2 observations (W1/W2; W1/W3; W2/W3; W1/W2/W3) were eligible for the analysis. A two-step procedure was conducted: first, individual age-dependent DM trajectories were calculated using linear mixed regressions based on random intercept (hours/day) and linear slopes (hours/day/year) and used as exposure measures in association with MetS at a second step. Trajectories were further dichotomized if children increased their DM duration over time above or below the mean. RESULTS: 10,359 children and adolescents (20,075 total observations, 50.3% females, mean age = 7.9, SD = 2.7) were included. DM exposure increased as children grew older (from 2.2 h/day at 2 years to 4.2 h/day at 16 years). Estonian children showed the steepest DM increase; Spanish children the lowest. The prevalence of MetS at last follow-up was 5.5%. Increasing media use trajectories were positively associated with z-scores of MetS (slope: ß = 0.54, 95%CI = 0.20-0.88; intercept: ß = 0.07, 95%CI = 0.02-0.13), and its components after adjustment for puberty, diet and other confounders. Children with increasing DM trajectories above mean had a 30% higher risk of developing MetS (slope: OR = 1.30, 95%CI = 1.04-1.62). Boys developed steeper DM use trajectories and higher risk for MetS compared to girls. CONCLUSIONS: Digital media use appears to be a risk factor for the development of MetS in children and adolescents. These results are of utmost importance for pediatricians and the development of health policies to prevent cardio-metabolic disorders later in life. TRIAL REGISTRATION: ISRCTN, ISRCTN62310987 . Registered 23 February 2018- retrospectively registered.

Circulating miRNAs are associated with sleep duration in children/adolescents: Results of the I.Family Study.

NEW FINDINGS: What is the central question of this study? Are differential patterns of circulating miRNAs associated with sleep duration in normal-weight European children and adolescents? What is the main finding and its importance? Differences in the expression level of circulating miR-26b-3p and miR-485-5p are positively associated with total sleep duration in healthy normal-weight children and adolescents. ABSTRACT: It is commonly recognized that sleep is essential for children's health, and that insufficient sleep duration is associated with negative health outcomes. In humans, sleep duration and quality are influenced by genetic, environmental and social factors. Epigenetic mechanisms, likewise, regulate circadian rhythms and sleep patterns. In the present study, we aimed to identify circulating microRNAs associated with sleep duration in a subsample of normal-weight European children/adolescents (n = 111) participating in the I.Family Study. Subjects were divided into two groups based upon self-reported sleep duration, according to the recommended amount of sleep for paediatric populations. Sleep needs for children <13 years were at least 9 h per day, and for children >13 were at least 8 h per day. There were group differences (short sleepers versus normal sleepers) in circulating levels of miR-26b-3p (mean (95% CI) = 2.0 (1.3-2.7) versus 2.3 (1.9-2.7), P = 0.05) and miR-485-5p (mean (95% CI) = 0.6 (0.3-0.9) versus 0.9 (0.7 - 1.0), P < 0.001), adjusting for country of origin, age, sex, pubertal status, screen time and highest educational level of parents. Our findings show for the first time that sleep duration reflects the profile of specific circulating microRNAs in school-aged children and adolescents. It is conceivable that epigenetic modifications, mainly related to circadian rhythm control, may be modulated or interfere with sleep duration.

A study of the dietary intake of Cypriot children and adolescents aged 6-18 years and the association of mother's educational status and children's weight status on adherence to nutritional recommendations.

BACKGROUND: A balanced diet is fundamental for healthy growth and development of children. The aim of this study was to document and evaluate the dietary intake of Cypriot children aged 6-18 years (y) against recommendations, and to determine whether maternal education and children's weight status are associated with adherence to recommendations. METHODS: The dietary intake of a random sample of 1414 Cypriot children was assessed using a 3-day food diary. Adherence to recommendations was estimated and the association of their mother's education and their own weight status on adherence were explored. RESULTS: A large percentage of children consumed less than the minimum of 45% energy (en) of carbohydrate (18.4%-66.5% in different age groups) and exceeded the recommended intakes of total fat (42.4%-83.8%), saturated fatty acids (90.4%-97.1%) and protein (65.2%-82.7%), while almost all (94.7%-100%) failed to meet the recommended fibre intake. Additionally, a large proportion of children (27.0%-59.0%) consumed >300 mg/day cholesterol and exceeded the upper limit of sodium (47.5%-78.5%). In children aged 9.0-13.9y, there was a high prevalence of inadequacy for magnesium (85.0%-89.9%), in girls aged 14.0-18.9y, of Vitamin A (25.3%), Vitamin B6 (21.0%) and iron (25.3%) and in boys of the same group, of Vitamin A (35.8%). Children whose mother was more educated were more likely to consume >15%en from protein, Odds Ratio (OR) 1.85 (95% CI:1.13-3.03) for mothers with tertiary education and exceed the consumption of 300 mg/day cholesterol (OR 2.13 (95% CI:1.29-3.50) and OR 1.84 (95% CI:1.09-3.09) for mothers with secondary and tertiary education respectively). Children whose mothers were more educated, were less likely to have Vitamin B1 (p<0.05) and Vitamin B6 intakes below the EAR (p < 0.05 for secondary school and p < 0.001 for College/University) and iron intake below the AI (p < 0.001). Overweight/obese children were more likely to consume >15%en protein (OR 1.85 (95% CI:1.26-2.71) and have a < Adequate Intake of calcium (OR 1.85 (95% CI:1.11-3.06)). CONCLUSION: Cypriot children consume a low quality diet. Maternal education and children's own weight status are associated with children's adherence to recommendations. Public health policies need to be evaluated to improve dietary quality and reduce disease burden.

The combination of daily breakfast consumption and optimal breakfast choices in childhood is an important public health message.

The aim of this study was to investigate the association of breakfast consumption with children's diet quality and cardiometabolic risk factors. Study sample consisted of 1558 children aged 4-8 years from Cyprus. Breakfast frequency was assessed through a parental questionnaire. Body mass index (BMI), BMI z-scores, waist circumference, blood lipid profile and blood pressure were examined in relation to breakfast frequency consumption. Habitual breakfast consumers' daily nutrient intake was assessed through a 24-Hour Dietary Recall, according to their breakfast choices. Girls who have breakfast on a daily basis had lower mean BMI and BMI z-score; they were also less likely of having abnormal levels of serum triglycerides, atheromatic index (total cholesterol to high density lipoprotein-cholesterol ratio) and diastolic blood pressure after controlling for several confounding factors. Within regular breakfast consumers, of both boys and girls, those having ready to eat cereals had a superior nutrient intake profile. Daily breakfast consumption along with good breakfast choices is an important public health message for Cypriot children.

Diet-obesity associations in children: approaches to counteract attenuation caused by misreporting.

OBJECTIVE: Measurement errors in dietary data lead to attenuated estimates of associations between dietary exposures and health outcomes. The present study aimed to compare and evaluate different approaches of handling implausible reports by exemplary analysis of the association between dietary intakes (total energy, soft drinks, fruits/vegetables) and overweight/obesity in children. DESIGN: Cross-sectional multicentre study. SETTING: Kindergartens/schools from eight European countries participating in the IDEFICS Study. SUBJECTS: Children (n 5357) aged 2-9 years who provided one 24 h dietary recall and complete covariate information. RESULTS: The 24 h recalls were classified into three reporting groups according to adapted Goldberg cut-offs: under-report, plausible report or over-report. In the basic logistic multilevel model (adjusted for age and sex, including study centre as random effect), the dietary exposures showed no significant association with overweight/obesity (energy intake: OR=0·996 (95 % CI 0·983, 1·010); soft drinks: OR = 0·999 (95 % CI 0·986, 1·013)) and revealed even a positive association for fruits/vegetables (OR = 1·009 (95 % CI 1·001, 1·018)). When adding the reporting group (dummy variables) and a propensity score for misreporting as adjustment terms, associations became significant for energy intake as well as soft drinks (energy: OR = 1·074 (95 % CI 1·053, 1·096); soft drinks: OR = 1·015 (95 % CI 1·000, 1·031)) and the association between fruits/vegetables and overweight/obesity pointed to the reverse direction compared with the basic model (OR = 0·993 (95 % CI 0·984, 1·002)). CONCLUSIONS: Associations between dietary exposures and health outcomes are strongly affected or even masked by measurement errors. In the present analysis consideration of the reporting group and inclusion of a propensity score for misreporting turned out to be useful tools to counteract attenuation of effect estimates.

Television habits in relation to overweight, diet and taste preferences in European children: the IDEFICS study.

Early television exposure has been associated with various health outcomes including childhood obesity. This paper describes associations between patterns of television viewing, on one hand, and diet, taste preference and weight status, on the other, in European preschoolers and schoolchildren. The IDEFICS baseline survey was conducted at examination centers in Italy, Estonia, Cyprus, Belgium, Sweden, Germany, Hungary, and Spain. 15,144 children aged 2-9 completed the basic protocol, including anthropometry and parental questionnaires on their diets and television habits. A subsample of 1,696 schoolchildren underwent further sensory testing for fat and sweet taste preferences. Three dichotomous indicators described: children's habitual television exposure time; television viewing during meals; and having televisions in their bedrooms. Based on these variables we investigated television habits in relation to overweight (IOTF) and usual consumption of foods high in fat and sugar. A possible role of taste preference in the latter association was tested in the sensory subgroup. All television indicators were significantly associated with increased risk of overweight, with odds ratios ranging from 1.21 to 1.30, in fully adjusted models. Children's propensities to consume high-fat and high-sugar foods were positively and, in most analyses, monotonically associated with high-risk television behaviors. The associations between television and diet propensities were not explained by preference for added fat or sugar in test foods. To summarize, in addition to being more overweight, children with high-risk television behaviors may, independent of objectively measured taste preferences for fat and sugar, passively overconsume higher-fat and particularly higher-sugar diets.

Circulating miRNAs Are Associated with Inflammation Biomarkers in Children with Overweight and Obesity: Results of the I.Family Study.

Increasing data suggest that overnutrition-induced obesity may trigger an inflammatory process in adipose tissue and upturn in the innate immune system. Numerous players have been involved in governing the inflammatory response, including epigenetics. Among epigenetic players, miRNAs are emerging as crucial regulators of immune cell development, immune responses, autoimmunity, and inflammation. In this study, we aimed at identifying the involvement of candidate miRNAs in relation to inflammation-associated biomarkers in a subsample of European children with overweight and obesity participating in the I.Family study. The study sample included individuals with increased adiposity since this condition contributes to the early occurrence of chronic low-grade inflammation. We focused on the acute-phase reagent C-reactive protein (CRP) as the primary outcome and selected cytokines as plausible biomarkers of inflammation. We found that chronic low-grade CRP elevation shows a highly significant association with miR-26b-3p and hsa-miR-576-5p in boys. Furthermore, the association of CRP with hsa-miR-10b-5p and hsa-miR-31-5p is highly significant in girls. We also observed major sex-related associations of candidate miRNAs with selected cytokines. Except for IL-6, a significant association of hsa-miR-26b-3p and hsa-miR-576-5p with TNF-α, IL1-Ra, IL-8, and IL-15 levels was found exclusively in boys. The findings of this exploratory study suggest sex differences in the association of circulating miRNAs with inflammatory response biomarkers, and indicate a possible role of miRNAs among the candidate epigenetic mechanisms related to the process of low-grade inflammation in childhood obesity.

Prospective physical fitness status and development of cardiometabolic risk in children according to body fat and lifestyle behaviours: The IDEFICS study.

BACKGROUND: Elevated cardiometabolic risk (CMR) is an important factor for cardiovascular diseases later in life while physical fitness seems to decrease CMR. OBJECTIVE: Thus, the aim of the present study is to assess the association between muscular fitness (MF) and cardiorespiratory fitness (CRF) on CMR in European children, both cross-sectional and longitudinally. METHODS: A total of 289 children (49.5% males) from eight European countries, aged 6 to 9, with longitudinal information on blood pressure, triglycerides, total cholesterol, HDL-cholesterol, homoeostasis model assessment, body mass index, data on fitness level, objectively measured physical activity (PA), diet quality, and total screen time were included. A CMR score was calculated and dichotomized. MF and CRF were also dichotomized. Cross-sectional and longitudinal multilevel logistic regressions adjusting for lifestyle behaviours were performed. RESULTS: Reaching a high level of MF during childhood as well as remaining in that level over-time were associated with an 82% and 62% lower probability of high CMR at follow-up, respectively. Also, children who became top CRF over time, showed a 77% lower probability (P < 0.05) of being in the highest CMR quartile at follow-up, independently of sociodemographic and lifestyle indicators. CONCLUSIONS: A high MF at early childhood and during childhood reduces the odds of having CMR. Same occurs with the improvement of CRF during childhood. These findings highlight the importance of enhancing fitness to avoid CMR already in children.

Pre-obese children's dysbiotic gut microbiome and unhealthy diets may predict the development of obesity.

It is widely accepted that the intestinal microbiome is connected to obesity, as key mediator of the diet impact on the host metabolic and immunological status. To investigate whether the individual gut microbiome has a potential in predicting the onset and progression of diseases, here we characterized the faecal microbiota of 70 children in a two-time point prospective study, within a four-year window. All children had normal weight at the beginning of this study, but 36 of them gained excessive weight at the subsequent check-up. Microbiome data were analysed together with the hosts' diet information, physical activity, and inflammatory parameters. We find that the gut microbiota structures were stratified into a discrete number of groups, characterized by different biodiversity that correlates with inflammatory markers and dietary habits, regardless of age, gender, and body weight. Collectively, our data underscore the importance of the microbiome-host-diet configuration as a possible predictor of obesity.

Dietary Patterns of European Children and Their Parents in Association with Family Food Environment: Results from the I.Family Study.

The aim of this study was to determine whether an association exists between children's  and  parental  dietary  patterns  (DP),  and  whether  the  number  of  shared  meals  or  soft  drink  availability  during  meals  strengthens  this  association.  In  2013/2014  the  I.Family  study  cross-sectionally assessed the dietary intakes of families from eight European countries using 24-h  dietary recalls. Usual energy and food intakes from six- to 16-year-old children and their parents  were estimated based on the NCI Method. A total of 1662 child-mother and 789 child-father dyads  were included; DP were derived using cluster analysis. We investigated the association between  children's and parental DP and whether the number of shared meals or soft drink availability  moderated this association using mixed effects logistic regression models. Three DP comparable in  children and parents were obtained: Sweet & Fat, Refined Cereals, and Animal Products. Children  were more likely to be allocated to the Sweet & Fat DP when their fathers were allocated to the  Sweet & Fat DP and when they shared at least one meal per day (OR 3.18; 95% CI 1.84; 5.47). Being  allocated to the Sweet & Fat DP increased when the mother or the father was allocated to the Sweet  & Fat DP and when soft drinks were available (OR 2.78; 95% CI 1.80; 4.28 or OR 4.26; 95% CI 2.16;  8.41, respectively). Availability of soft drinks and negative parental role modeling are important  predictors of children's dietary patterns.

Urinary Mineral Concentrations in European Pre-Adolescent Children and Their Association with Calcaneal Bone Quantitative Ultrasound Measurements.

This study investigates differences and associations between urinary mineral concentrations and calcaneal bone measures assessed by quantitative ultrasonography (QUS) in 4322 children (3.1-11.9 years, 50.6% boys) from seven European countries. Urinary mineral concentrations and calcaneal QUS parameters differed significantly across countries. Clustering revealed a lower stiffness index (SI) in children with low and medium urinary mineral concentrations, and a higher SI in children with high urinary mineral concentrations. Urinary sodium (uNa) was positively correlated with urinary calcium (uCa), and was positively associated with broadband ultrasound attenuation and SI after adjustment for age, sex and fat-free mass. Urinary potassium (uK) was negatively correlated with uCa but positively associated with speed of sound after adjustment. No association was found between uCa and QUS parameters after adjustment, but when additionally adjusting for uNa, uCa was negatively associated with SI. Our findings suggest that urinary mineral concentrations are associated with calcaneal QUS parameters and may therefore implicate bone properties. These findings should be confirmed in longitudinal studies that include the food intake and repeated measurement of urinary mineral concentrations to better estimate usual intake and minimize bias.

A Common Variant and the Transcript Levels of MC4R Gene Are Associated With Adiposity in Children: The IDEFICS Study.

CONTEXT: The melanocortin-4 receptor gene (MC4R) plays a pivotal role in the regulation of body fat and food and energy intake. OBJECTIVES: The objectives of the study were as follows: 1) to evaluate the association of variants rs17782313 and rs17700633 near the coding region of MC4R and 2) to evaluate the association of the transcript levels of MC4R with adiposity indices and percentage of energy from fat, carbohydrates, and protein in children. DESIGN: The Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants (IDEFICS) cohort was used, with examinations at baseline (T0) and after 2 years (T1). SETTING AND PARTICIPANTS: A total of 16 228 schoolchildren (2-9 y) from eight European countries participated in the study. A random sample of 4381 children genotyped for MC4R variants and a subsample of 410 children with MC4R expression data in peripheral blood cells (PBCs) were included in the analyses. MAIN OUTCOME MEASURES: Anthropometric measures and energy intake (total and from fat, carbohydrates, and protein) served as outcomes for adiposity status and for dietary behavior, respectively. RESULTS: At T0, the C allele of rs17782313 (minor frequency allele 23%) was significantly associated with higher values of adiposity indices (all P < .001). No association was found between rs17700633 (minor frequency allele 28%) and the variables under study. At T1, the C allele of rs17782313 was associated with a significantly higher increase in the adiposity indices over time (all P < .05). The MC4R expression levels in PBCs were inversely associated with body fat and energy intake from carbohydrates and directly with energy from fat (all P ≤ .05) but were not influenced by variants rs17782313 and rs17700633. CONCLUSIONS: The common variant rs17782313 near MC4R was cross-sectionally and longitudinally associated with body mass index and measures of body fatness in children aged 2-9 years. We showed, for the first time in humans, that MC4R expression levels in PBCs are related to body fat distribution and percentage of energy intake from carbohydrates and fat.

Dietary Carbohydrate and Nocturnal Sleep Duration in Relation to Children's BMI: Findings from the IDEFICS Study in Eight European Countries.

Previous research has found an association between being overweight and short sleep duration. We hypothesized that this association could be modified by a high carbohydrate (HC) diet and that the timing and type (starch or sugar) of intake may be an important factor in this context. Participants in the prospective, eight-country European study IDEFICS were recruited from September 2007 to June 2008, when they were aged two to nine years. Data on lifestyle, dietary intake and anthropometry were collected on two occasions. This study included 5944 children at baseline and 4301 at two-year follow-up. For each meal occasion (morning, midday, and evening), starch in grams and sugar in grams were divided by total energy intake (EI), and quartiles calculated. HC-starch and HC-sugar intake categories were defined as the highest quartile for each meal occasion. In a mutually adjusted linear regression model, short sleep duration as well as HC-starch in the morning were positively associated with body mass index (BMI) z-scores at baseline. HC-starch at midday was positively associated with body mass index (BMI) z-scores in children with short sleep duration, and negatively associated with BMI z-scores in those with normal sleep. After adjustment for baseline BMI z-scores, associations between total HC from starch or sugar and high BMI z-scores at two-year follow-up did not persist. Our observations offer a perspective on optimal timing for macronutrient consumption, which is known to be influenced by circadian rhythms. Reduced carbohydrate intake, especially during morning and midday meals, and following nocturnal sleep duration recommendations are two modifiable factors that may protect children from being overweight in the future.

Peer effects on obesity in a sample of European children.

This study analyzes peer effects on childhood obesity using data from the first two waves of the IDEFICS study, which applies several anthropometric and other measures of fatness to approximately 14,000 children aged two to nine participating in both waves in 16 regions of eight European countries. Peers are defined as same-sex children in the same school and age group. The results show that peer effects do exist in this European sample but that they differ among both regions and different fatness measures. Peer effects are larger in Spain, Italy, and Cyprus--the more collectivist regions in our sample--while waist circumference generally gives rise to larger peer effects than BMI. We also provide evidence that parental misperceptions of their own children's weight goes hand in hand with fatter peer groups, supporting the notion that in making such assessments, parents compare their children's weight with that of friends and schoolmates.

Overweight and obesity prevalence and trends in children and adolescents in Cyprus 2000-2010.

OBJECTIVES: To estimate the prevalence of overweight and obesity in 2010 and examine prevalence trends between 2000 and 2010 among school-aged children and adolescents in Cyprus. METHODS: A representative cross-sectional study was undertaken in 2010. Anthropometric data were taken using standard methods from 3090 children. The IOTF cut-offs were used to define overweight and obese participants, and prevalence was compared with a previous representative study performed in 2000. Prevalences with 95% confidence intervals (95% CI) were calculated and logistic regression models were used to estimate 10-year trends. RESULTS: The overall prevalence of obesity was higher in 2010 (8.1% [95%CI: 7.1, 9.1]) compared to 2000 (5.9% [95%CI: 5.0, 6.8]), p=0.002. The overall prevalence of overweight was also higher in 2010 (20.1% [95%CI: 18.7, 21.5]) compared to 2000 (16.5% [95%CI: 15.0, 18.0]), p<0.001. The prevalence of obesity increased at a greater rate in school-aged boys (p=0.017), and in rural areas (p=0.001). In rural areas, high maternal education background is associated with a decreased odds for obesity; odds ratio 0.35 (95% CI: 0.17, 0.69), p=0.003. CONCLUSIONS: The prevalence of obesity and overweight in children and adolescents in Cyprus has increased substantially over a decade, mainly in rural areas and in school-aged boys.

Migrant background and weight gain in early infancy: results from the German study sample of the IDEFICS study.

OBJECTIVE: To examine variations in infant weight gain between children of parents with and without migrant background and to investigate how these differences are explained by pre- and perinatal factors. METHODS: We used data on birth weight and weight at six months from well-child check-up books that were collected from a population-based German sample of children in the IDEFICS study (n = 1,287). We calculated unadjusted and adjusted means for weight z-scores at birth and six months later. We applied linear regression for change in weight z-score and we calculated odds ratios and 95% confidence intervals (95% CI) for rapid weight gain by logistic regression, adjusted for biological, social and behavioural factors. RESULTS: Weight z-scores for migrants and Germans differed slightly at birth, but were markedly increased for Turkish and Eastern European infants at age six months. Turkish infants showed the highest change in weight z-score during the first 6 months (ß = 0.35; 95% CI 0.14-0.56) and an increased probability of rapid weight gain compared with German infants. Examination of the joint effect of migrant and socioeconomic status (SES) showed the greatest change in weight z-scores in Turkish infants from middle SES families (ß = 0.77; 95% CI 0.40-1.14) and infants of parents from Eastern European countries with high SES (ß = 0.72; 95% CI 0.13-1.32). CONCLUSIONS: Our results support the hypothesis that migrant background is an independent risk factor for infant weight gain and suggest that the onset of health inequalities in overweight starts in early infancy.

Understanding the links among neuromedin U gene, beta2-adrenoceptor gene and bone health: an observational study in European children.

Neuromedin U, encoded by the NMU gene, is a hypothalamic neuropeptide that regulates both energy metabolism and bone mass. The beta-2 adrenergic receptor, encoded by the ADRB2 gene, mediates several effects of catecholamine hormones and neurotransmitters in bone. We investigated whether NMU single nucleotide polymorphisms (SNPs) and haplotypes, as well as functional ADRB2 SNPs, are associated with bone stiffness in children from the IDEFICS cohort, also evaluating whether NMU and ADRB2 interact to affect this trait. A sample of 2,274 subjects (52.5% boys, age 6.2 ± 1.8 years) from eight European countries, having data on calcaneus bone stiffness index (SI, mean of both feet) and genotyping (NMU gene: rs6827359, rs12500837, rs9999653; ADRB2 gene: rs1042713, rs1042714), was studied. After false discovery rate adjustment, SI was significantly associated with all NMU SNPs. rs6827359 CC homozygotes showed the strongest association (recessive model, Δ= -1.8, p=0.006). Among the five retrieved haplotypes with frequencies higher than 1% (range 2.0-43.9%), the CCT haplotype (frequency=39.7%) was associated with lower SI values (dominant model, Δ= -1.0, p=0.04) as compared to the most prevalent haplotype. A non-significant decrease in SI was observed in in ADRB2 rs1042713 GG homozygotes, while subjects carrying SI-lowering genotypes at both SNPs (frequency = 8.4%) showed much lower SI than non-carriers (Δ= -3.9, p<0.0001; p for interaction=0.025). The association was more evident in preschool girls, in whom SI showed a curvilinear trend across ages. In subgroup analyses, rs9999653 CC NMU or both GG ADRB2 genotypes were associated with either lower serum calcium or ß-CrossLaps levels (p=0.01). This study in European children shows, for the first time in humans, a role for NMU gene through interaction with ADRB2 gene in bone strength regulation, more evident in preschool girls.

Prevalence of overweight and obesity among 11-year-old children in Cyprus, 1997-2003.

OBJECTIVES: To report 5-year changes in the prevalence of overweight and obesity in 11-year-old children in Cyprus. METHODS: This was a school-based study performed in Cyprus. A total of 14,090 11-year-old children (males: 51.2%), who had been examined in the 1997-8 and 2002-3 school years, were included in the study. The International Obesity Task Force (IOTF) cut-offs were used to define overweight and obese subjects, and logistic regression models were used to estimate 5-year trends. RESULTS: The overall prevalence of overweight children was slightly higher in the second period but this change was not statistically significant. There was only a significant increase in overweight boys in rural areas; odds ratio (OR) (95% confidence interval [CI]) for the 5-year period was 1.33 (1.10, 1.62; p = 0.004). The overall relative increase in obesity was 17.9% and the OR (95% CI) was 1.22 (1.07, 1.38; p = 0.003). Although the prevalence of obesity was higher in males in both periods, the relative increase was substantially higher in females, 29.6% vs. 11.4%. The relative increase was also higher in rural (35.9%) compared with urban areas (8.7%); ORs (95% CI) 1.46 (1.17, 1.81) vs. 1.10 (0.94, 1.29), respectively. CONCLUSIONS: This is the first report documenting increasing rates of obesity among school-aged children in Cyprus. Females and children living in rural areas experienced the most striking increases. The prevalence of overweight increased only in males living in rural areas.