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1.
Diagnosis accuracy of waist-to-height ratio to predict cardiometabolic risk in children with obesity.
Muñoz-Hernando, J, Luque, V, Ferré, N, Feliu, A, Closa-Monasterolo, R, Gutiérrez-Marin, D, Basora, J, Pedraza, A, Salvado, O, Vidal-Piedra, S, et al
Pediatric research. 2023;(5):1294-1301
Abstract
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.
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2.
Effect of Protein Intake Early in Life on Kidney Volume and Blood Pressure at 11 Years of Age.
Parada-Ricart, E, Ferre, N, Luque, V, Gruszfeld, D, Gradowska, K, Closa-Monasterolo, R, Koletzko, B, Grote, V, Escribano Subías, J
Nutrients. 2023;(4)
Abstract
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 (β = 8.71, 95%CI 0.09-17.33, p = 0.048) and higher systolic blood pressure (β = 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.
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3.
Effect of maternal smoking during pregnancy on child blood pressure in a European cohort.
Parada-Ricart, E, Luque, V, Zaragoza, M, Ferre, N, Closa-Monasterolo, R, Koletzko, B, Grote, V, Gruszfeld, D, Verduci, E, Xhonneux, A, et al
Scientific reports. 2022;(1):17308
Abstract
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.
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4.
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.
Totzauer, M, Escribano, J, Closa-Monasterolo, R, Luque, V, Verduci, E, ReDionigi, A, Langhendries, JP, Martin, F, Xhonneux, A, Gruszfeld, D, et al
Pediatric obesity. 2022;(12):e12961
Abstract
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.
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5.
Association of Protein Intake during the Second Year of Life with Weight Gain-Related Outcomes in Childhood: A Systematic Review.
Ferré, N, Luque, V, Closa-Monasterolo, R, Zaragoza-Jordana, M, Gispert-Llauradó, M, Grote, V, Koletzko, B, Escribano, J
Nutrients. 2021;(2)
Abstract
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.
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6.
Validation of bioelectrical impedance analysis for body composition assessment in children with obesity aged 8-14y.
Gutiérrez-Marín, D, Escribano, J, Closa-Monasterolo, R, Ferré, N, Venables, M, Singh, P, Wells, JC, Muñoz-Hernando, J, Zaragoza-Jordana, M, Gispert-Llauradó, M, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(6):4132-4139
Abstract
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.
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7.
A novel approach to assess body composition in children with obesity from density of the fat-free mass.
Gutiérrez-Marín, D, Escribano, J, Closa-Monasterolo, R, Ferré, N, Venables, M, Singh, P, Wells, JCK, Muñoz-Hernando, J, Zaragoza-Jordana, M, Gispert-Llauradó, M, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(3):1102-1107
Abstract
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.
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8.
Fibre Intake Is Associated with Cardiovascular Health in European Children.
Larrosa, S, Luque, V, Grote, V, Closa-Monasterolo, R, Ferré, N, Koletzko, B, Verduci, E, Gruszfeld, D, Xhonneux, A, Escribano, J
Nutrients. 2020;(1)
Abstract
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.
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9.
Impact of infant protein supply and other early life factors on plasma metabolome at 5.5 and 8 years of age: a randomized trial.
Kirchberg, FF, Hellmuth, C, Totzauer, M, Uhl, O, Closa-Monasterolo, R, Escribano, J, Gruszfeld, D, Gradowska, K, Verduci, E, Mariani, B, et al
International journal of obesity (2005). 2020;(1):69-81
Abstract
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.
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10.
Are All Breast-fed Infants Equal? Clustering Metabolomics Data to Identify Predictive Risk Clusters for Childhood Obesity.
Kirchberg, FF, Grote, V, Gruszfeld, D, Socha, P, Closa-Monasterolo, R, Escribano, J, Verduci, E, Mariani, B, Langhendries, JP, Poncelet, P, et al
Journal of pediatric gastroenterology and nutrition. 2019;(3):408-415
Abstract
OBJECTIVES Fetal and early life represent a period of developmental plasticity during which metabolic pathways are modified by environmental and nutritional cues. Little is known on the pathways underlying this multifactorial complex. We explored whether 6 months old breast-fed infants could be clustered into metabolically similar groups and that those metabotypes could be used to predict later obesity risk. METHODS Plasma samples were obtained from 183 breast-fed infants aged 6 months participating in the European multicenter Childhood Obesity Project study. We measured amino acids along with polar lipid concentrations (acylcarnitines, lysophosphatidylcholines, phosphatidylcholines, sphingomyelins). We determined the metabotypes using a Bayesian agglomerative clustering method and investigated the properties of these clusters with respect to clinical, programming, and metabolic factors up to 6 years of age. RESULTS We identified 20 metabolite clusters comprising 1 to 39 children. Phosphatidylcholines predominantly influenced the clustering process. In the largest clusters (n ≥ 14), large differences existed for birth length (unadjusted P < 0.0001) and length and weight at 6 months (unadjusted P < 0.0001 and P = 0.012, respectively). Infants tended to cluster together by country (unadjusted P < 0.001). The body mass index (BMI) z score at 6 years of age tended to differ (unadjusted P = 0.07). CONCLUSIONS Our exploratory study provided evidence that breast-fed infants are not metabolically homogeneous and that variation in metabolic profiles among infants may provide insight into later development and health. This work highlights the potential of metabotypes for identifying inter-individual differences that may form the basis for developing personalized early preventive strategies.