Esther M. González-Gil

High‐sensitivity C‐reactive Protein is a Predictive Factor of Adiposity in Children: Results of the Identification and prevention of Dietary‐ and lifestyle‐induced health Effects in Children and InfantS (IDEFICS) Study

Background Whereas cross‐sectional studies have shown that obesity is associated with increased C‐reactive protein (CRP) levels in children, little is known about the impact of low‐grade inflammation on body mass changes during growth. Methods and Results We assessed cross‐sectionally and longitudinally the association of high‐sensitivity (hs)‐CRP levels with overweight/obesity and related cardiometabolic risk factors in the Identification and prevention of Dietary‐ and lifestyle‐induced health Effects in Children and InfantS (IDEFICS) cohort. 16 224 children from 8 European countries (2 to 9 years) were recruited during the baseline survey (T0). After the exclusion of 7187 children because of missing hs‐CRP measurements and 2421 because of drug use during the previous week, the analysis was performed on 6616 children (Boys=3347; Girls=3269; age=6.3±1.7 years). Of them, 4110 were reexamined 2 years later (T1). Anthropometric variables, blood pressure, hs‐CRP, blood lipids, glucose and insulin were measured. The population at T0 was divided into 3 categories, according to the baseline hs‐CRP levels. Higher hs‐CRP levels were associated with significantly higher prevalence of overweight/obesity, body mass index (BMI) z‐score and central adiposity indices (P values all <0.0001), and with higher blood pressure and lower HDL‐cholesterol levels. Over the 2‐year follow‐up, higher baseline hs‐CRP levels were associated with a significant increase in BMI z‐score (P<0.001) and significantly higher risk of incident overweight/obesity. Conclusions Higher hs‐CRP levels are associated to higher body mass and overweight/obesity risk in a large population of European children. Children with higher baseline levels of hs‐CRP had a greater increase in BMI z‐score and central adiposity over time and were at higher risk of developing overweight/obesity during growth.

Reliability of primary caregivers reports on lifestyle behaviours of European pre‐school children: the ToyBox‐study

Reliable assessments of health‐related behaviours are necessary for accurate evaluation on the efficiency of public health interventions. The aim of the current study was to examine the reliability of a self‐administered primary caregivers questionnaire (PCQ) used in the ToyBox‐intervention. The questionnaire consisted of six sections addressing sociodemographic and perinatal factors, water and beverages consumption, physical activity, snacking and sedentary behaviours. Parents/caregivers from six countries (Belgium, Bulgaria, Germany, Greece, Poland and Spain) were asked to complete the questionnaire twice within a 2‐week interval. A total of 93 questionnaires were collected. Test–retest reliability was assessed using intra‐class correlation coefficient (ICC). Reliability of the six questionnaire sections was assessed. A stronger agreement was observed in the questions addressing sociodemographic and perinatal factors as opposed to questions addressing behaviours. Findings showed that 92% of the ToyBox PCQ had a moderate‐to‐excellent test–retest reliability (defined as ICC values from 0.41 to 1) and less than 8% poor test–retest reliability (ICC < 0.40). Out of the total ICC values, 67% showed good‐to‐excellent reliability (ICC from 0.61 to 1). We conclude that the PCQ is a reliable tool to assess sociodemographic characteristics, perinatal factors and lifestyle behaviours of pre‐school children and their families participating in the ToyBox‐intervention.

Abdominal fat and metabolic risk in obese children and adolescents

The aim of this study was to investigate fat distribution, mainly abdominal fat, and its relationship with metabolic risk variables in a group of 126 children and adolescents (60 males and 66 females) aged 5.0 to 14.9. According to IOTF criteria, 46 were classified as normal weight, 28 overweight and 52 obese. Weight, height, waist (WC) and hip circumferences were measured. The body mass index (BMI) was calculated. Total body fat, trunkal and abdominal fat were also assessed by dual energy x-ray absorptiometry (DXA). Glucose, insulin, HDL-Cholesterol, triglycerides (TG), ferritine, homocystein and C-reactive protein (CRP) were measured. Obesity status was related with insulin concentrations, CRP, TG and HDL. Obese patients had higher abdominal fat and higher CRP values than overweight and normal subjects. All markers of central body adiposity were related with insulin and lipid metabolism; however, they were not related with homocystein or ferritin. A simple anthropometric measurement, like waist circumference, seems to be a good predictor of the majority of the obesity related metabolic risk variables.

Serum transaminases concentrations in obese children and adolescents.

The aim of the study was to investigate the relationship between liver transaminase levels and metabolic syndrome (MS) features in obese children and adolescents. A total of 132 children and adolescents (73 males and 59 females) aged 8–16, participated in the study. All were studied at the department of Paediatrics, University Hospital of Zaragoza (Spain). Inclusion criteria were the existence of obesity as defined by body mass index (BMI) according to Cole cut-off values (when BMI was higher than the age and sex specific equivalent to 30 kg/m2). The definition of metabolic syndrome was according to the International Diabetes Federation criteria. Weight (kg), height (cm), waist circumference (cm), blood pressure and BMI were measured. Laboratory determinations after overnight fasting included: transaminases (ALT, AST, GGT), fasting glucose, insulin, triglycerides and HDL-C. The MS was found in 21.6% of the obese children and adolescents and the prevalence was higher in males (25.9%) than in females (15.9%). Serum transaminases (ALT, AST and GGT) mean concentrations were higher in males than in females, and decreased during pubertal development. The obese children and adolescents with the MS did not show higher transaminases concentrations when compared with those without the MS. Some MS manifestations (mainly waist circumference) showed a correlation with ALT, although all transaminases values were normal according to adult references. Liver transaminases, a surrogate marker of NAFLD, did not show an early and consistent manifestation of abnormalities in the obese children and adolescents studied. In order to define the presence of the disease, it would be necessary to obtain aminotransferase reference standards for children and adolescents, considering pubertal stage and gender.ResumenSe valora en el estudio la concentración de transaminasas en niños y adolescentes obesos y se investiga la relación entre enzimas hepáticas y marcadores de síndrome metabólico (SM). Un total de 132 niños y adolescentes (73 chicos y 59 chicas), de 8–16 años, participaron en el estudio. El criterio de inclusión fue la existencia de obesidad definida mediante el índice de masa corporal (IMC) de acuerdo con los valores de Coleet al. (IMC mayor que el equivalente a 30 kg/m2 para una edad y sexo específico). Para definir el síndrome metabólico (MS), se eligieron los criterios de la Federación Internacional de Diabetes. Se realizaron medidas del peso (Kg), altura (cm), perímetro de la cintura y tensión arterial y determinaciones de laboratorio en ayunas de las transaminasas (ALT, AST, GGT), glucosa, insulina, triglicéridos y HDL-C. Presentaron síndrome metabólico el 21,6% de los niños y adolescentes obesos y la prevalencia fue mayor en chicos (25,9%) que en chicas (15,9%). Los componentes más frecuentes del síndrome metabólico fueron la obesidad abdominal (exceso de circunferencia de cintura, 93%) y la tensión arterial elevada (34,3%). Los valores medios de las concentraciones séricas de transaminasas (ALT, AST, GGT) fueron mayores en chicos que en chicas, y disminuyeron según el desarrollo puberal. Los niños y adolescentes obesos con síndrome metabólico no presentaron mayores concentraciones de transaminasas en comparación con los que no tenían síndrome metabólico. Algunas manifestaciones de SM (en particular el perímetro de la cintura) se asociaron con ALT, aunque los valores de transaminasas fueron normales según las referencias usadas para adultos. En los niños estudiados, las transaminasas, un marcador secundario de hígado graso no-alcohólico (NAFLD), no fueron una manifestación temprana y consistente de estas anomalías. Para definir la presencia de la enfermedad, sería necesario obtener valores de referencia de transaminasas para niños y adolescentes, considerando el estadío puberal y el sexo.

Folate and Vitamin B12 concentrations are associated with plasma DHA and EPA fatty acids in European adolescents: The Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study

This study aimed to examine the association between vitamin B6, folate and vitamin B12 biomarkers and plasma fatty acids in European adolescents. A subsample from the Healthy Lifestyle in Europe by Nutrition in Adolescence study with valid data on B-vitamins and fatty acid blood parameters, and all the other covariates used in the analyses such as BMI, Diet Quality Index, education of the mother and physical activity assessed by a questionnaire, was selected resulting in 674 cases (43 % males). B-vitamin biomarkers were measured by chromatography and immunoassay and fatty acids by enzymatic analyses. Linear mixed models elucidated the association between B-vitamins and fatty acid blood parameters (changes in fatty acid profiles according to change in 10 units of vitamin B biomarkers). DHA, EPA) and n-3 fatty acids showed positive associations with B-vitamin biomarkers, mainly with those corresponding to folate and vitamin B12. Contrarily, negative associations were found with n-6:n-3 ratio, trans-fatty acids and oleic:stearic ratio. With total homocysteine (tHcy), all the associations found with these parameters were opposite (for instance, an increase of 10 nmol/l in red blood cell folate or holotranscobalamin in females produces an increase of 15·85 µmol/l of EPA (P value <0·01), whereas an increase of 10 nmol/l of tHcy in males produces a decrease of 2·06 µmol/l of DHA (P value <0·05). Positive associations between B-vitamins and specific fatty acids might suggest underlying mechanisms between B-vitamins and CVD and it is worth the attention of public health policies.

Establishing a method to estimate the cost-effectiveness of a kindergarten-based, family-involved intervention to prevent obesity in early childhood. The ToyBox-study

Overweight and obesity in children are recognized as a major health problem. The ToyBox‐intervention was developed with the aim of preventing obesity in pre‐schoolers. Because it is increasingly important to inform policy makers not only on the effects of prevention interventions, but also on their costs and cost‐effectiveness, our purpose was to establish a method to estimate the cost‐effectiveness of the ToyBox‐intervention. In order to estimate the long‐term impact of the ToyBox‐intervention on health and societal costs, extrapolations of the intervention effect will be conducted to predict childrens weight status (based on the body mass index) at adult age. Effects of the adult weight status on the prevalence of obesity‐related complications will be modelled through a Markov model, with a total time horizon of 70 years and a cycle length of 1 year. The model will be conducted in six European countries participating in the ToyBox‐intervention, based on country‐specific economic and epidemiological data. This study describes the methodological rationale and implementation of an analytic model to examine the cost‐effectiveness of the ToyBox‐intervention for six European countries, in order to inform decision‐makers on the value for money of this intervention in the prevention of obesity in pre‐schoolers.

Analysis of the association of leptin and adiponectin concentrations with metabolic syndrome in children: Results from the IDEFICS study

BACKGROUND AND AIMS Adipokines may play a role in the pathogenesis of the metabolic syndrome (MetS) in children. We aimed to evaluate the association of leptin, adiponectin, and its ratio (L/A ratio) with the metabolic syndrome (MetS) in a subsample of the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS) cohort. METHODS AND RESULTS Leptin, adiponectin and MetS parameters were measured in a subsample of 1253 children (3-9.9 years) participating to the IDEFICS study, grouped as: Non-OW (underweight/normal weight) and OW/Ob (overweight/obese). MetS was defined using the sex- and age-specific cut-offs based on the distribution of MetS components in the IDEFICS cohort. The prevalence of the MetS among OW/Ob was 24.8% and 27.1% in boys and girls respectively, whereas ≤2% among Non-OW. OW/Ob had significantly higher leptin and L/A ratio as compared to Non-OW. Significantly higher leptin was found in OW/Ob with MetS as compared with OW/Ob without MetS. Significantly lower adiponectin was observed only in OW/Ob girls as compared to Non-OW. A 1SD increase in leptin and L/A ratio z-scores or a 1SD decrease in adiponectin z-score were significantly associated with higher risk of MetS. After adjustment for BMI or body fat mass (BFM) the association remained significant only for leptin. CONCLUSION We showed that in European children, higher leptin concentration is associated with MetS, even after adjusting for BMI or BFM, confirming an early role of leptin in MetS, while the association of adiponectin with MetS seems be mediated by body fat in this age range.

C-reactive protein reference percentiles among pre-adolescent children in Europe based on the IDEFICS study population

Objectives:C-reactive protein (CRP) is involved in a wide range of diseases. It is a powerful marker for inflammatory processes used for diagnostic and monitoring purposes. We aimed to establish reference values as data on the distribution of serum CRP levels in young European children are scarce.Subjects:Reference values of high-sensitivity CRP concentrations were calculated for 9855 children aged 2.0–10.9 years, stratified by age and sex. The children were recruited during the population-based European IDEFICS study (Identification and prevention of Dietary- and lifestyle-induced health Effects in Children and infantS) with 18 745 participants recruited from 2007 to 2010.Results:In 44.1 % of the children, CRP values were below or equal the detection limit of 0.2 mg/l. Median CRP concentrations showed a slight negative age trend in boys and girls, whereas serum CRP values were slightly higher in girls than in boys across all age groups.Conclusions:Our population-based reference values of CRP may guide paediatric practice as elevated values may require further investigation or treatment. Therefore, the presented reference values represent a basis for clinical evaluation and for future research on risk assessment of diseases associated with increased CRP levels among children.

Whole-blood fatty acids and inflammation in European children: the IDEFICS Study

Background/Objectives:Fatty acids are hypothesized to influence cardiovascular disease risk because of their effect on inflammation. The aim of this study is to assess the relationship between whole-blood fatty acids (WBFAs) and high-sensitivity C-reactive protein (hs-CRP) in European children.Subjects/Methods:A total of 1401 subjects (697 boys and 704 girls) aged between 2 and 9 years from the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects in Children and infantS) study were measured in this cross-sectional analysis. The sample was divided into three categories of hs-CRP. Associations between WBFA and hs-CRP were assessed by logistic regression models adjusting for body mass index (BMI), country, age, breastfeeding, mother’s education and hours of physical activity.Results:Linoleic acid (LA) (P=0.013, 95% confidence interval (CI): 0.822–0.977) and sum of n-6 WBFA (P=0.029, 95% CI: 0.866–0.992) concentrations were associated with lower concentrations of hs-CRP in boys. In girls, a high ratio of eicosapentaenoic acid (EPA)/arachidonic acid (AA) was associated (P=0.018, 95% CI: 0.892–0.989) with lower hs-CRP concentrations. In contrast, sum of blood n-6 highly unsaturated fatty acids (P=0.012, 95% CI: 1.031–1.284), AA (P=0.007, 95% CI: 1.053–1.395) and AA/LA ratio (P=0.005, 95% CI: 1.102–1.703) were associated (P<0.05) with higher concentrations of hs-CRP in girls.Conclusions:The n-6 WBFAs (sum of n-6 FA and LA) were associated with lower hs-CRP in boys and with higher hs-CRP in girls (AA, sum of n-6 highly unsaturated and AA/LA ratio). More studies are needed to identify the optimal levels of WBFAs to avoid low-grade inflammation in children considering the differences by sex and BMI.

Prospective associations between dietary patterns and high sensitivity C-reactive protein in European children: the IDEFICS study

PurposeThis prospective study explores high sensitivity C-reactive protein (hs-CRP) levels in relation to dietary patterns at two time points in European children.MethodsOut of the baseline sample of the IDEFICS study (n = 16,228), 4020 children, aged 2–9 years at baseline, with available hs-CRP levels and valid data from a food frequency questionnaire (FFQ) at baseline (T0) and 2 years later (T1) were included. K-means clustering algorithm based on the similarities between relative food consumption frequencies of the FFQ was applied. hs-CRP was dichotomized according to sex-specific cutoff points. Multilevel logistic regression was performed to assess the relationship between dietary patterns and hs-CRP adjusting for covariates.ResultsThree consistent dietary patterns were found at T0 and T1: ‘animal protein and refined carbohydrate’, ‘sweet and processed’ and ‘healthy’. Children allocated to the ‘protein’ and ‘sweet and processed’ clusters at both time points had significantly higher odds of being in the highest category of hs-CRP (OR 1.47; 95% CI 1.03–2.09 for ‘animal protein and refined carbohydrate’ and OR 1.44; 95% CI 1.08–1.92 for ‘sweet and processed’) compared to the ‘healthy’ cluster. The odds remained significantly higher for the ‘sweet and processed’ pattern (OR 1.39; 95% CI 1.05–1.84) when covariates were included.ConclusionsA dietary pattern characterized by frequent consumption of sugar and processed products and infrequent consumption of vegetables and fruits over time was independently related with inflammation in European children. Efforts to improve the quality of the diet in childhood may prevent future diseases related with chronic inflammation.