Impact of the motivational interviewing for childhood obesity treatment: The Obemat2.0 randomized clinical trial.

BACKGROUND AND OBJECTIVE: The aim was assessing a short training for healthcare providers on patient-focused counselling to treat childhood obesity in primary care, along with dietitian-led workshops and educational materials. METHODS: Randomized clustered trial conducted with paediatrician-nurse pairs (Basic Care Units [BCU]) in primary care centres from Tarragona (Spain). BCUs were randomized to intervention (MI) (motivational interview, dietitian-led education, and educational materials) or control group (SC, standard care). Participants were 8-14-year-old children with obesity, undergoing 1-11 monthly treatment visits during 1 year at primary care centres. The primary outcome was BMI z-score reduction. RESULTS: The study included 44 clusters (23 MI). Out of 303 allocated children, 201 (n = 106 MI) completed baseline, final visits, and at least one treatment visit and were included in the analysis. BMI z-score reduction was -0.27 (±0.31) in SC, versus -0.36 (±0.35) in MI (p = 0.036). Mixed models with centres as random effects showed greater reductions in BMI in MI than SC; differences were B = -0.11 (95% CI: -0.20, -0.01, p = 0.025) for BMI z-score, and B = -2.06 (95% CI: -3.89, -0.23, p = 0.028) for BMI %. No severe adverse events related to the study were notified. CONCLUSION: Training primary care professionals on motivational interviewing supported by dietitians and educational materials, enhanced the efficacy of childhood obesity therapy.

Airway surface liquid pH in paediatric patients with cystic fibrosis / PH del líquido de la vía aérea en pacientes pediátricos con fibrosis quística

Background: Cystic fibrosis (CF) patients have more acidic airway surface liquid (ASL), which can denature antimicrobial defensins. Induced sputum is non-invasive and is as representative as bronchoalveolar lavage. Objectives: The objectives of this study were to analyse the ASL pH obtained by induced sputum and assess the relationship between clinical features in paediatric CF patients. Methods: This is a prospective observational study in CF paediatric patients. Sputum was induced in a patient by inhaling 4.5% hypertonic saline, the sputum was collected into a sterile container for pathological analysis, and the pH was measured from the liquid part (ASL) in a gas machine. Results: A total of 27 patients were included in the study: mean age (11.96 ± 3.9) years, mean sweat test (99.38 ± 17.76) ng/L, common mutation Del508F (N24, 88.8%), mean FEV1% 91.94% ± –12.6%, Staphylococcus colonization 14 (51.9%), normal chest CT 8 (29.6%), air trapping 12 (44.4%), bronchiectasis 6 (22.2%), and mean ASL pH 6.72 ± 0.06 (n = 15). A significant correlation was found between a higher sweat test and lower ASL pH (R = 0.683, p = 0.005). There were no differences between altered chest CT (p = 0.199) and positive Staphylococcus aureus (p = 0.17). Conclusion: This is the first publication that use induced sputum to obtain the ASL pH in CF patients. The ASL pH in CF patients is usually acidic and correlated with altered transmembrane function conductance. (AU)

Antecedentes: Los pacientes con fibrosis quística (FQ) tienen el líquido de la vía aérea (ASL) ácido, provocando desnaturalización de defensinas antimicrobianas. El esputo inducido es reproducible, no invasivo y la muestra es equiparable al lavado broncoalveolar. Objetivo: Evaluar el pH ASL obtenido por esputo inducido y analizar sus implicaciones clínicas, en niños FQ. Métodos: Estudio observacional prospectivo desarrollado en niños FQ. El esputo se indujo mediante inhalación de solución salina hipertónica 4,5%. Se recolectó el esputo y posterior al análisis patológico el ASL se colocó en una jeringa y se midió pH con una máquina de gases. Resultados: Se incluyeron 27 pacientes: edad (11,96 ± 3,9) años, test del sudor (99,38 ± 17,76) ng/L, variante común Del508F (N24, 88,8%), FEV1% 91,94% ± 12,6%, Staphylococcus 14 (51,9%), TAC pulmonar normal 8 (29,6%), atrapamiento 12 (44,4%), bronquiectasias 6 (22,2%), pH ASL 6,72 ± 0,06 (n = 15). Se observó correlación significativa entre niveles elevados del test del sudor y pH ASL ácido (R = 0,683, p = 0,005). No hubo correlación entre pH ASL y TAC pulmonar alterado (p = 0,199) o S. aureus positivo (p = 0,17). Conclusiones: Esta es la primera publicación que utiliza esputo inducido para medir pH del ASL en FQ. El pH ASL se correlacionó con la alteración del gen de conductancia transmembranal. (AU)

Effect of Protein Intake Early in Life on Kidney Volume and Blood Pressure at 11 Years of Age.

High protein intake has been associated with kidney hypertrophy, which is usually reversible; however, when it occurs early in life, it could lead to cell programming with a long-lasting effect. This study aimed to assess whether higher protein ingestion early in life has a persistent effect on kidney volume at 11 years of age, as well as its influence on blood pressure. This is a secondary analysis of a randomized control trial that compared the growth of infants fed with a higher-protein formula versus those fed with a lower-protein formula, with a control group of breastfed infants. Renal ultrasound and anthropometric measurements were assessed at 6 months and 11 years of age. At 11 years, urinary protein, albumin and creatinine, and blood pressure were measured in 232 children. Feeding with a higher-protein formula was associated with a larger kidney volume (ß = 8.71, 95%CI 0.09-17.33, p = 0.048) and higher systolic blood pressure (ß = 3.43, 95%CI 0.78-6.08, p = 0.011) at 11 years of age. Microalbuminuria was detected in 7% of the patients, with no differences among groups (p = 0.56). The effect of increased protein ingestion early in life may condition kidney volume and blood pressure in later childhood.

Diagnosis accuracy of waist-to-height ratio to predict cardiometabolic risk in children with obesity.

BACKGROUND: Waist-to-height ratio (WHtR) predicts abdominal fat and cardiometabolic risk. In children with obesity, the most adequate cut-off to predict cardiometabolic risk as well as its ability to predict risk changes over time has not been tested. Our aim was to define an appropriate WHtR cut-off to predict cardiometabolic risk in children with obesity, and to analyze its ability to predict changes in cardiometabolic risk over time. METHODS: This is an observational prospective study secondary to the OBEMAT2.0 trial. We included data from 218 participants (8-15 years) who attended baseline and final visits (12 months later). The main outcome measure was a cardiometabolic risk score derived from blood pressure, lipoproteins, and HOMA index of insulin resistance. RESULTS: The optimal cut-off to predict the cardiometabolic risk score was WHtR ≥0.55 with an area under the curve of 0.675 (95% CI: 0.589-0.760) at baseline and 0.682 (95% CI: 0.585-0.779) at the final visit. Multivariate models for repeated measures showed that changes in cardiometabolic risk were significantly associated with changes in WHtR. CONCLUSION: This study confirms the clinical utility of WHtR to predict changes in cardiometabolic risk over time in children with obesity. The most accurate cut-off to predict cardiometabolic risk in children with obesity was WHtR ≥0.55. IMPACT: In children, there is no consensus on a unique WHtR cut-off to predict cardiometabolic risk. The present work provides sufficient evidence to support the use of the 0.55 boundary. We have a large sample of children with obesity, with whom we compared the previously proposed boundaries according to cardiometabolic risk, and we found the optimal WHtR cut-off to predict it. We also analyzed if a reduction in the WHtR was associated with an improvement in their cardiometabolic profile.

Different protein intake in the first year and its effects on adiposity rebound and obesity throughout childhood: 11 years follow-up of a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Infant feeding affects child growth and later obesity risk. We examined whether protein supply in infancy affects the adiposity rebound, body mass index (BMI) and overweight and obesity up to 11 years of age. METHODS: We enrolled healthy term infants from five European countries in a double blind randomized trial, with anticipated 16 examinations within 11 years follow-up. Formula-fed infants (n = 1090) were randomized to isoenergetic formula with higher or lower protein content within the range stipulated by EU legislation in 2001. A breastfed reference group (n = 588) was included. Adiposity rebound and BMI trajectories were estimated by generalized additive mixed models in 917 children, with 712 participating in the 11 year follow-up. RESULTS: BMI trajectories were elevated in the higher compared to the lower protein group, with significantly different BMI at adiposity rebound (0.24 kg/m2, 0.01-0.47, p = 0.040), and an increased risk for overweight at 11 years (adjusted Odds Ratio 1.70; 1.06-2.73; p = 0.027) but no significant difference for obesity (adjusted Odds Ratio 1.47; 0.66-3.27). The two formula groups did not differ in the timing of adiposity rebound, but all children with obesity at 11 years had an early adiposity rebound before four years. CONCLUSIONS: Compared to conventional high protein formula, feeding lower protein formula in infancy lowers BMI trajectories up to 11 years and achieves similar BMI values at adiposity rebound as observed in breastfed infants.

Effect of maternal smoking during pregnancy on child blood pressure in a European cohort.

Hypertension is a public health issue that can have its origin in the early phases of development. Maternal smoking during pregnancy (MSDP) could play a role in offspring's cardio-metabolic programming. To assess the relationship between MSDP and later blood pressure (BP) in children we conducted a secondary analysis of a randomized dietary intervention trial (EU-Childhood Obesity Project). Healthy term infants with normal birth weight were recruited during the first 8 weeks of life in 5 European countries and followed until 11 years of age. Data on MSDP was collected at recruitment. BP and anthropometry were assessed at 11 years of age. Children were classified according to AAP guidelines as normal BP: BP < 90th percentile; high BP: ≥ 90th percentile with the subset of children having BP > 95th percentile categorized as hypertensive. Out of 572 children, 20% were exposed to MSDP. At 11 years, 26.8% had BP over the 90th centile. MSDP beyond 12 weeks of gestation was associated with higher systolic BP percentile (adjusted B 6.935; 95% CI 0.454, 13.429; p = 0.036) and over twofold increase likelihood of hypertension (OR 2.195; 95% CI 1.089, 4.423; p = 0.028) in children at 11 years. MSDP was significantly associated with later BP in children.

Parental Perception of Body Weight Status of Their 8-year-old Children: Findings from the European CHOP Study.

BACKGROUND: Maternal perception of child weight status in children with overweight or obesity has received a lot of attention but data on paternal perception of children from presumably healthy cohorts are lacking. OBJECTIVE: We aimed to investigate paternal and maternal perception of child weight status at the age of 8 years in a cohort of 591 children from 5 European countries. MATERIAL AND METHODS: Included were 8-year-old children and their parents participating in the European Childhood Obesity Project (EU CHOP). Weight and height of children and parents were measured and Body Mass Index (BMI, kg/m2) was calculated. Both parents were asked to assess their perception of child weight status using Eckstein scales and their concern about child overweight. The agreement between mother and father perceptions was assessed by Cohen kappa coefficient and their relationship was analyzed by linear mixed effects models based on ordinal logistic regression, accounting for country, child gender and BMI, parental BMI, level of education, concern and type of feeding during first year of life. RESULTS: Data from children and both parents were available for 432 girls and boys. Mean BMI was comparable in boys and girls (16.7 ± 2.31 vs. 16.9 ± 2.87 kg/m2, P = 0.55). In total, 172 children (29.3%) were overweight or obese. There was a high degree of agreement between mother and father perceptions of their child's weight status (Cohen kappa 0.77). Multivariate modelling showed that perception levels significantly increased with child BMI but were globally lower than assessed. They differed between countries, gender and types of feeding during first year of life, were influenced by education level of the father but were not related to parental BMI and concern about childhood overweight. CONCLUSIONS: The study showed no overall differences between mothers and fathers in rating their child's weight status but both parents had a propensity to underestimate their child's actual weight, particularly in boys. The EU CHOP trial registered at clinicaltrials.gov as NCT00338689.

Usefulness of the waist-to-height ratio for predicting cardiometabolic risk in children and its suggested boundary values.

BACKGROUND & AIMS: Only limited information is available on the usefulness of the waist-to-height ratio (WHtR) as an abdominal obesity marker in children. Our aim was to compare the ability of a WHtR >90th percentile, a WHtR ≥0.50, a WHtR ≥0.55 and a BMI z-score ≥2 SD to predict cardiometabolic risk in children followed-up at different ages. METHODS: We evaluated data from 660 children at 5, 8 and 11 years of age who participated in the Childhood Obesity Project trial in 5 European countries. We classified children with or without cardiometabolic (CMet) risk (yes vs. no) according to the presence of ≥2 parameters (blood pressure, HOMA-IR, triglyceride levels and high-density lipoprotein (HDL) cholesterol levels) ≥90th percentile. RESULTS: The odds ratio for CMet risk in children at all followed-up ages was statistically significant for all measures. The OR for the WHtR≥0.55 cut-off was 29.1 (5.6, 151.7) at 5 years of age, 11.8 (4.1, 33.8) at 8 year of age and 3.6 (1.7, 7.7) at 11 years of age, compared to the WHtR<0.55 cut-off. The WHtR≥0.55 cut-off showed a higher OR at younger ages than the BMI z-score ≥2SD, WHtR ≥90th percentile and WHtR≥0.50 cut-offs and a higher positive predictive value (82% at 5 years of age compared to 55%, 36% and 41%, respectively). CONCLUSION: A WHtR≥0.55 is a suitable cut-off for screening children at high cardiometabolic risk in the general young European population.

Sleep duration and problem behaviour in 8-year-old children in the Childhood Obesity Project.

There is growing evidence that insufficient sleep has negative effects on the mental health of children. The aim of this study is to examine the associations between device-measured sleep duration and internalizing and externalizing problems in 8-year-old children. The study is a secondary analysis of data from the Childhood Obesity Project conducted in five European countries. Nocturnal sleep duration was measured with the SenseWear™ Armband 2. Parents rated their child's internalizing and externalizing problems on the Child Behaviour Checklist. Behaviour scores were dichotomized at the 90th percentile based on sex- and country-specific z-scores. Logistic regression models were applied to test the associations between sleep duration and behaviour. Data were available for 406 8-year-old children. The average sleep duration was 9.25 h per night (SD: 0.67) with 1464 nights measured in total. The sleep duration recommendation of the American Academy of Sleep Medicine for school-aged children (9-12 h) was met by 66.7% of children. One hour of additional sleep per night significantly reduced the risk of having internalizing problems (adjusted OR = 0.51; 95% CI 0.29-0.91). Children who adhered to the sleep duration recommendation had a lower risk for internalizing problems (adjusted OR = 0.45; 95% CI 0.21-0.99). Sleep duration and externalizing problems showed no significant association. Longer sleep duration was associated with a reduced risk of having internalizing problems but not externalizing problems. Results highlight that it is important to ensure adequate sleep duration throughout primary-school years for the optimal emotional health of children. Trial registration number: NCT00338689. Registered: June 19, 2006.

Dietary patterns acquired in early life are associated with cardiometabolic markers at school age.

BACKGROUND & AIMS: it has previously been described that dietary patterns established early in life tracked to late childhood. The aim of the present work was to analyse the association of dietary patterns that tracked from 2 to 8y with cardiometabolic markers at 8y of age. METHODS: The 3 identified patterns at 2y (that previous analyses showed to track to age 8y) were: "CoreDP", loaded for vegetables, fruits, fish, olive oil, etc.; "F&SDP", loaded by poor-quality fats and sugars; and "ProteinDP", mainly loaded by animal protein sources. Cardiometabolic markers at 8y were systolic blood pressure (SBP), insulin resistance (HOMA-IR), and triglycerides, and BMI z-score. To examine whether the association of diet with the outcomes was the result of a direct effect of diet at either two or 8y, or synergy between them, we used structural equation models. RESULTS: the associations between the patterns and the health outcomes were: CoreDP was inversely associated with SBP and HOMA-IR; ProteinDP was directly associated with HOMA-IR and SBP; and adherence to F&SDP was directly associated with triglycerides and SBP. The associations between the patterns and the health outcomes were independent of BMI and were the result of a direct effect of diet at 2y, an indirect effect of diet at 2y through diet at 8y or a combination between both pathways. CONCLUSION: dietary patterns acquired in early life, persisting to later childhood, were associated with cardiometabolic markers at school age independently of BMI.

Validation of bioelectrical impedance analysis for body composition assessment in children with obesity aged 8-14y.

BACKGROUND & AIMS: The aim was to generate a predictive equation to assess body composition (BC) in children with obesity using bioimpedance (BIA), and avoid bias produced by different density levels of fat free mass (FFM) in this population. METHODS: This was a cross-sectional validation study using baseline data from a randomized intervention trial to treat childhood obesity. Participants were 8 to 14y (n = 315), underwent assessments on anthropometry and BC through Air Displacement Plethysmography (ADP), Dual X-Ray Absorptiometry and BIA. They were divided into a training (n = 249) and a testing subset (n = 66). In addition, the testing subset underwent a total body water assessment using deuterium dilution, and thus obtained results for the 4-compartment model (4C). A new equation to estimate FFM was created from the BIA outputs by comparison to a validated model of ADP adjusted by FFM density in the training subset. The equation was validated against 4C in the testing subset. As reference, the outputs from the BIA device were also compared to 4C. RESULTS: The predictive equation reduced the bias from the BIA outputs from 14.1% (95%CI: 12.7, 15.4) to 4.6% (95%CI: 3.8, 5.4) for FFM and from 18.4% (95%CI: 16.9, 19.9) to 6.4% (95% CI: 5.3, 7.4) for FM. Bland-Altman plots revealed that the new equation significantly improved the agreement with 4C; furthermore, the observed trend to increase the degree of bias with increasing FM and FFM also disappeared. CONCLUSION: The new predictive equation increases the precision of BC assessment using BIA in children with obesity.

Association of Protein Intake during the Second Year of Life with Weight Gain-Related Outcomes in Childhood: A Systematic Review.

There is accumulating evidence that early protein intake is related with weight gain in childhood. However, the evidence is mostly limited to the first year of life, whereas the high-weight-gain-velocity period extends up to about 2 years of age. We aimed to investigate whether protein intake during the second year of life is associated with higher weight gain and obesity risk later in childhood. We conducted a systematic review with searches in both PubMed®/MEDLINE® and the Cochrane Central Register of Controlled Trials. Ten studies that assessed a total of 46,170 children were identified. We found moderate-quality evidence of an association of protein intake during the second year of life with fat mass at 2 years and at 7 years. Effects on other outcomes such as body mass index (BMI), obesity risk, or adiposity rebound onset were inconclusive due to both heterogeneity and low evidence. We conclude that higher protein intakes during the second year of life are likely to increase fatness in childhood, but there is limited evidence regarding the association with other outcomes such as body mass index or change in adiposity rebound onset. Further well-designed and adequately powered clinical trials are needed since this issue has considerable public health relevance.

A novel approach to assess body composition in children with obesity from density of the fat-free mass.

BACKGROUND & AIMS: Assessment of Fat Mass (FM) and fat-free mass (FFM) using Air-displacement plethysmography (ADP) technique assumes constant density of FFM (DFFM) by age and sex. It has been recently shown that DFFM further varies according to body mass index (BMI), meaning that ADP body composition assessments of children with obesity could be biased if DFFM is assumed to be constant. The aim of this study was to validate the use of the calculations of DFFM (rather than constant density of the FFM) to improve accuracy of body composition assessment in children with obesity. METHODS: cross-sectional validation study in 66 children with obesity (aged 8-14 years) where ADP assessments of body composition assuming constant density (FFMBODPOD and FMBODPOD) were compared to those where DFFM was adjusted in relation to BMI (FFMadjusted and FMadjusted), and both compared to the gold standard reference, the 4-component model (FFM4C and FM4C). RESULTS: FFMBODPOD was overestimated by 1.50 kg (95%CI -0.68 kg, 3.63 kg) while FFMadjusted was 0.71 kg (-1.08 kg, 2.51 kg) (percentage differences compared to FFM4C were 4.9% (±2.9%) and 2.8% (±2.1%), respectively (p < 0.001)). Consistently, FM was underestimated by both methods, representing a mean difference between methods of 4.0% (±2.9%) and 6.8% (±3.8%), respectively, when compared to the reference method. The agreement and reliability of body composition assessments were improved when adjusted using calculations (adjusted models) rather than assuming constant DFFM. CONCLUSIONS: The use of constant values for fat-free mass properties may increase bias when assessing body composition (FM and FFM) in children with obesity by two-component techniques such as ADP. Using adjusted corrections as proposed in the present work may reduce the bias by half.

Fibre Intake Is Associated with Cardiovascular Health in European Children.

BACKGROUND: We aimed at analysing the association between dietary fibre intake during childhood and cardiovascular health markers. METHODS: We used observational longitudinal analysis and recorded diet using 3-day diaries at the ages of 3, 4, 5, 6, and 8 years in children from the EU Childhood Obesity Project Trial. At the age of 8, waist circumference, systolic and diastolic blood pressure (SBP and DBP) and biochemical analyses (lipoproteins, triglycerides and homeostasis model for insulin resistance (HOMA-IR)) were evaluated. Those parameters were combined into a cardiometabolic risk score through the sum of their internal z-scores. RESULTS: Four-hundred children (51.8% girls) attended to the 8-year visit with a 3-day diary. Adjusted linear regression models showed that children who repeatedly stayed in the lowest tertile of fibre intake during childhood had higher HOMA-IR (p = 0.004), higher cardiometabolic risk score (p = 0.02) and a nonsignificant trend toward a higher SBP at 8 years. The higher the dietary intake of soluble fibre (from fruits and vegetables) at 8 years, the lower the HOMA-IR and the cardiometabolic risk score (p = 0.002; p = 0.004). SBP was directly associated with fibre from potatoes and inversely with fibre from nuts and pulses. CONCLUSION: A diet rich in dietary fibre from fruits, vegetables, pulses and nuts from early childhood was associated to a healthier cardiovascular profile, regardless of children's weight.

Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.

Effects of screen time and playing outside on anthropometric measures in preschool aged children.

OBJECTIVE: In view of the current obesity epidemic, studies focusing on the interplay of playing outside (PO), screen time (ST) and anthropometric measures in preschool age are necessary to guide evidence-based public health planning. We therefore investigated the relationship between average time spent PO and ST from the ages 3 to 6 years and anthropometric measures at 6 years of age. METHODS: PO and ST of 526 children of the European Childhood Obesity Project (CHOP) were annually assessed by questionnaire from 3 until 6 years of age. Body weight, waist circumference and height were measured at 3 and 6 years of age to calculate Body-Mass-Index z-Scores (zBMI) and waist-to-height ratio (WTH). Linear, logistic and quantile regressions were used to test whether average time spent PO and ST in the 4 year period had an effect on anthropometric measures at age 6 years. RESULTS: Longer daily ST was associated with a higher zBMI (P = 0.002) and WTH (P = 0.001) at 6 years of age. No significant associations were found for time spent PO. Each additional hour of average ST during the 4 year period resulted in a 66% higher risk of having a zBMI score over 1 (P < 0.001) and almost twice the risk (94% higher risk) of having an zBMI score over 2 (P < 0.001) at 6 years. CONCLUSIONS: Excessive ST during preschool age is a risk factor for increased zBMI at 6 years, regardless of time spent PO. Reducing high levels of ST during preschool age, for e.g. at least 1h per week, could help preventing childhood obesity.

Impact of infant protein supply and other early life factors on plasma metabolome at 5.5 and 8 years of age: a randomized trial.

OBJECTIVES: A high dairy protein intake in infancy, maternal pre-pregnancy BMI, and delivery mode are documented early programming factors that modulate the later risk of obesity and other health outcomes, but the mechanisms of action are not understood. METHODS: The Childhood Obesity Project is a European multicenter, double-blind, randomized clinical trial that enrolled healthy infants. Participating infants were either breastfed (BF) or randomized to receive higher (HP) or lower protein (LP) content formula in the first year of life. At the ages 5.5 years (n = 276) and 8 years (n = 232), we determined plasma metabolites by liquid chromatography tandem-mass-spectrometry of which 226 and 185 passed quality control at 5.5 years and 8 years, respectively. We assessed the effects of infant feeding, maternal pre-pregnancy BMI, smoking in pregnancy, delivery mode, parity, birth weight and length, and weight gain (0-24 months) on the metabolome at 5.5 and 8 years. RESULTS: At 5.5 years, plasma alpha-ketoglutarate and the acylcarnitine/BCAA ratios tended to be higher in the HP than in the LP group, but no metabolite reached statistical significance (Pbonferroni>0.09). There were no group differences at 8 years. Quantification of the impact of early programming factors revealed that the intervention group explained 0.6% of metabolome variance at both time points. Except for country of residence that explained 16% and 12% at 5.5 years and 8 years, respectively, none of the other factors explained considerably more variance than expected by chance. CONCLUSIONS: Plasma metabolome was largely unaffected by feeding choice and other early programming factors and we could not prove the existence of a long term programming effect of the plasma metabolome.

An individual participant data meta-analysis on metabolomics profiles for obesity and insulin resistance in European children.

Childhood obesity prevalence is rising in countries worldwide. A variety of etiologic factors contribute to childhood obesity but little is known about underlying biochemical mechanisms. We performed an individual participant meta-analysis including 1,020 pre-pubertal children from three European studies and investigated the associations of 285 metabolites measured by LC/MS-MS with BMI z-score, height, weight, HOMA, and lipoprotein concentrations. Seventeen metabolites were significantly associated with BMI z-score. Sphingomyelin (SM) 32:2 showed the strongest association with BMI z-score (P = 4.68 × 10-23) and was also closely related to weight, and less strongly to height and LDL, but not to HOMA. Mass spectrometric analyses identified SM 32:2 as myristic acid containing SM d18:2/14:0. Thirty-five metabolites were significantly associated to HOMA index. Alanine showed the strongest positive association with HOMA (P = 9.77 × 10-16), while acylcarnitines and non-esterified fatty acids were negatively associated with HOMA. SM d18:2/14:0 is a powerful marker for molecular changes in childhood obesity. Tracing back the origin of SM 32:2 to dietary source in combination with genetic predisposition will path the way for early intervention programs. Metabolic profiling might facilitate risk prediction and personalized interventions in overweight children.

Correction to: longitudinal analysis of physical activity, sedentary behaviour and anthropometric measures from ages 6 to 11 years.

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