miR-130a expression is related to aortic dilation in bicuspid aortic valve children.

BACKGROUND: Bicuspid aortic valve disease (BAV) is present in 0.5-2% of the population and can promote aortic dilation, eventually leading to fatal consequences. Although some biomarkers have been proposed in adults, no studies have tested these candidates in children. We aimed to evaluate four miRNAs previously described to be related to BAV disease and aortic dilation in adults in a paediatric cohort. METHODS: Eighty participants ≤17 years old (4-17; mean 12) were included. From the BAV group, 40% had a dilated aorta (z score >2). RT‒qPCR were performed in plasma samples to quantify miR-122, miR-130a, miR-486, and miR-718 using the delta-delta Ct method. Functional and enrichment analyses of miR-130a were also performed. RESULTS: miR-130a expression in plasma was found to be significantly lower in BAV patients with a dilated aorta versus nondilated patients (p = 0.008) and healthy TAV controls (p = 0.004). Furthermore, miR-130a expression in plasma was inversely correlated with ascending aorta (r = 0.318, p = 0.004) and aortic root z scores (r = 0.322; p = 0.004). Enrichment analysis showed that miR-130a target genes are related to the TGFß signalling pathway. CONCLUSIONS: miR-130a expression in plasma is decreased in aortic-dilated BAV children compared to nondilated BAV children, helping differentiate low- to high-risk patients. IMPACT: miR-130a expression in plasma is related to aortic dilation in bicuspid aortic valve (BAV) children. To our knowledge, this is the first study that analyses miRNA patterns in bicuspid aortic valve children with aortic dilation. miR-130a expression in plasma could be a biomarker in order to help differentiate low-to high-risk BAV children, which is vitally important for advanced care planning.

Adherence to a healthy lifestyle behavior composite score and cardiometabolic risk factors in Spanish children from the CORALS cohort.

To assess the associations between the adherence to a composite score comprised of 6 healthy lifestyle behaviors and its individual components with several cardiometabolic risk factors in Spanish preschool children. Cross-sectional analyses were conducted in 938 participants included in the CORALS cohort aged 3-6 years. Six recognized healthy lifestyle behaviors (breastfeeding, sleep duration, physical activity, screentime, adherence to the Mediterranean diet, and eating speed) were assessed in a composite score. Multiple linear and logistic regression models were fitted to assess the associations with cardiometabolic risk factors (weight status, waist circumference, fat mass index, blood pressure, fasting plasma glucose, and lipid profile). In the adjusted multiple linear and logistic regression models, compared with the reference category of adherence to the healthy lifestyle behavior composite score, those participants in the category of the highest adherence showed significant decreased prevalence risk of overweight or obesity [OR (95% CI), 0.4 (0.2, 0.6)] as well as significant lower waist circumference, fat mass index (FMI), systolic blood pressure and fasting plasma glucose concentration [ß (95% CI), - 1.4 cm (- 2.5, - 0.4); - 0.3 kg/m2 (- 0.5, - 0.1); and - 3.0 mmHg (- 5.2, - 0.9); - 1.9 mg/dL (- 3.5, - 0.4), respectively]. Slow eating speed was individually associated with most of the cardiometabolic risk factors.   Conclusions: Higher adherence to the healthy lifestyle behavior composite score was associated with lower waist circumference, FMI, other cardiometabolic risk factors, and risk of overweight or obesity in Spanish preschool children. Further studies are required to confirm these associations. What is Known: • Lifestyle is a well-recognized etiologic factor of obesity and its comorbidities. • Certain healthy behaviors such as adhering to a healthy diet, increasing physical activity, and decreasing screentime are strategies for prevention and treatment of childhood obesity. What is New: • Higher adherence to the healthy lifestyle behavior composite score to 6 healthy behaviors (breastfeeding, sleep duration, physical activity, screentime, eating speed, and adherence to the Mediterranean diet) was associated with decreased adiposity, including prevalence risk of overweight or obesity, and cardiometabolic risk in preschool children. • Slow eating and greater adherence to the Mediterranean diet were mainly associated to lower fasting plasma and serum triglycerides concentration, respectively.

Role of dexamethasone in controlling the proinflammatory cytokine cascade in the first episode of paediatric acute pyelonephritis.

AIM: Febrile urinary tract infection is a common bacterial infection in childhood. The kidney damage after acute pyelonephritis (APN) could be related to the stimulation of the proinflammatory response. We aimed to investigate the role of inflammatory cytokines and the effect of dexamethasone after a first episode of APN. METHODS: Subanalysis of the DEXCAR RCT in which children with confirmed APN (1 month-14 years) were randomly assigned to receive a 3 days course of either intravenous dexamethasone or placebo. Urinary cytokine levels at diagnosis and after 72 h of treatment were measured. RESULTS: Ninety-two patients were recruited. Younger patients, males and those with abnormalities in the ultrasound study or vesicoureteral reflux showed higher values of urinary cytokines. Patients with severe APN had higher Tumour Necrosis Factor (TNF)α levels (81.0 ± 75.8 vs. 33.6 ± 48.5 pg/mg creatinine, p = 0.015). Both intervention groups showed similar basal clinical characteristics, including urinary cytokine levels. Treatment reduced urinary cytokine levels irrespective of dexamethasone administration. Neither the intervention group nor the urinary cytokine levels modulated the development of kidney scars. CONCLUSION: Basal urinary cytokines were associated with age, abnormal ultrasound and vesicoureteral reflux. Patients with severe APN had higher TNFa urinary levels. Administration of dexamethasone in children with APN does not improve the control of the proinflammatory cytokine cascade.

Associations Between Eating Speed, Diet Quality, Adiposity, and Cardiometabolic Risk Factors.

OBJECTIVE: To assess the associations between eating speed, adiposity, cardiometabolic risk factors, and diet quality in a cohort of Spanish preschool-children. STUDY DESIGN: A cross-sectional study in 1371 preschool age children (49% girls; mean age, 4.8 ± 1.0 years) from the Childhood Obesity Risk Assessment Longitudinal Study (CORALS) cohort was conducted. After exclusions, 956 participants were included in the analyses. The eating speed was estimated by summing the total minutes used in each of the 3 main meals and then categorized into slow, moderate, or fast. Multiple linear and logistic regression models were fitted to assess the ß-coefficient, or OR and 95% CI, between eating speed and body mass index, waist circumference, fat mass index (FMI), blood pressure, fasting plasma glucose, and lipid profile. RESULTS: Compared with participants in the slow-eating category, those in the fast-eating category had a higher prevalence risk of overweight/obesity (OR, 2.9; 95% CI, 1.8-4.4; P < .01); larger waist circumference (ß, 2.6 cm; 95% CI, 1.5-3.8 cm); and greater FMI (ß, 0.3 kg/m2; 95% CI, 0.1-0.5 kg/m2), systolic blood pressure (ß, 2.8 mmHg; 95% CI, 0.6-4.9 mmHg), and fasting plasma glucose levels (ß, 2.7 mg/dL, 95% CI, 1.2-4.2 mg/dL) but lower adherence to the Mediterranean diet (ß, -0.5 points; 95% CI, -0.9 to -0.1 points). CONCLUSIONS: Eating fast is associated with higher adiposity, certain cardiometabolic risk factors, and lower adherence to a Mediterranean diet. Further long-term and interventional studies are warranted to confirm these associations.

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.

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.

Dexamethasone to prevent kidney scarring in acute pyelonephritis: a randomized clinical trial.

BACKGROUND: Urinary tract infection (UTI) is one of the most common bacterial infections in childhood and is associated with long-term complications. We aimed to assess the effect of adjuvant dexamethasone treatment on reducing kidney scarring after acute pyelonephritis (APN) in children. METHODS: Multicenter, prospective, double-blind, placebo-controlled, randomized clinical trial (RCT) where children from 1 month to 14 years of age with proven APN were randomly assigned to receive a 3-day course of either an intravenous corticosteroid (dexamethasone 0.30 mg per kg/day) twice daily or placebo. The late technetium 99 m-dimercaptosuric acid scintigraphy (> 6 months after acute episode) was performed to assess kidney scar persistence. Kidney scarring risk factors (vesicoureteral reflux, kidney congenital anomalies, or urinary tract dilatation) were also assessed. RESULTS: Ninety-one participants completed the follow-up and were finally included (dexamethasone n = 49 and placebo n = 42). Both groups had similar baseline characteristics. Twenty participants showed persistent kidney scarring after > 6 months of follow-up without differences in incidence between groups (22% and 21% in the dexamethasone and placebo groups, p = 0.907). Renal damage severity in the early DMSA (ß = 0.648, p = 0.023) and procalcitonin values (ß = 0.065 p = 0.027) significantly modulated scar development. Vesicoureteral reflux grade showed a trend towards significance (ß = 0.545, p = 0.054), but dexamethasone treatment showed no effect. CONCLUSION: Dexamethasone showed no effect on reducing the risk of scar formation in children with APN. Hence, there is no evidence for an adjuvant corticosteroid treatment recommendation in children with APN. However, the study was limited by not achieving the predicted sample size and the expected scar formation. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02034851. Registered in January 14, 2014. "A higher resolution version of the Graphical abstract is available as Supplementary information."

Influence of total sugar intake on metabolic blood markers at 8 years of age in the Childhood Obesity Project.

PURPOSE: We aimed to characterize the association of dietary sugar intake with blood lipids and glucose-related markers in childhood. METHODS: Data from the multicentric European Childhood Obesity Project Trial were used. Three-day weighed dietary records were obtained at 8 years of age along with serum concentrations of triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), glucose, and insulin. Total sugar intake comprised all mono- and disaccharides; different sugar sources were defined. Linear regression models were applied to investigate the cross-sectional association of total sugar intake with blood lipids and glucose-related markers with adjustment for total energy intake using the residual method. RESULTS: Data were available for 325 children. Children consumed on average 332 kcal (SD 110) and 21% (SD 6) of energy from total sugar. In an energy-adjusted model, an increase of 100 kcal from total sugar per day was significantly associated with a z score HDL-C decrease (- 0.14; 95% CI - 0.01, - 0.27; p value = 0.031). Concerning different food groups of total sugar intake, 100 kcal total sugar from sweetened beverages was negatively associated with z score HDL-C (- 1.67; 95% CI - 0.42, - 2.91; p value = 0.009), while total sugar from milk products was positively related to z score HDL-C (1.38, 95% CI 0.03, 2.72; p value = 0.045). None of the other blood lipids or glucose-related markers showed a significant relationship with total sugar intake. CONCLUSION: Increasing dietary total sugar intake in children, especially from sweetened beverages, was associated with unfavorable effects on HDL-C, which might increase the long-term risk for dyslipidemia and cardiovascular disease. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT00338689; Registered: June 19, 2006. URL: https://clinicaltrials.gov/ct2/show/NCT00338689?term=NCT00338689&rank=1 .

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.

Associations of sugar intake with anthropometrics in children from ages 2 until 8 years in the EU Childhood Obesity Project.

PURPOSE: We determined the association of total sugar intake with body weight and fat mass in children on an energy-equivalent basis and potential changes in the association from 2 to 8 years of age. METHODS: Data were available from the Childhood Obesity Project Trial initiated in 2002. Sugar intake was measured by 3-day weighed food protocols at 2, 3, 4, 5, 6, and 8 years of age. Body mass index (BMI) and fat mass index (FMI) were available at the same time points. To investigate the association of sugar intake with anthropometrics over time, linear mixed models were applied. Odds ratios for having a high BMI or FMI (above one standard deviation) were estimated by logistic random-effects models. To control for total energy intake, the residual method was chosen and models were additionally adjusted for total energy intake. RESULTS: Data were available for 809 children with in total 2846 observations. In an isocaloric model, an increase of 100 kcal from sugar per day was significantly associated with lower zBMI (- 0.033; 95% CI -0.061, - 0.005) and zFMI (- 0.050; 95% CI - 0.089, - 0.011). In addition, a 100 kcal higher sugar intake was related to lower odds of having a high zBMI (OR 0.743; 95% CI 0.611, 0.903). CONCLUSION: This study provides no indication that increased total sugar intake positively affects BMI on an energy-equivalent basis. Whether the negative association of sugar is due to physiological effects or points more to macronutrient preferences or a reporting bias (lower sugar intake) in children with higher BMI can be debated. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT00338689; Registered: June 19, 2006. URL: http://clinicaltrials.gov/ct2/show/NCT00338689?term=NCT00338689&rank=1 .

Cultural effects on neurodevelopmental testing in children from six European countries: an analysis of NUTRIMENTHE Global Database.

Cultural background is an important variable influencing neuropsychological performance. Multinational projects usually involve gathering data from participants from different countries and/or different cultures. Little is known about the influence of culture on neuropsychological testing results in children and especially in European children. The objectives of this study were to compare neuropsychological performance of children from six European countries (Belgium, Germany, Italy, The Netherlands, Poland and Spain) using a comprehensive neuropsychological battery and to apply a statistical procedure to reduce the influence of country/cultural differences in neuropsychological performance. As expected, the results demonstrated differences in neuropsychological performance among children of the six countries involved. Cultural differences remained after adjusting for other confounders related to neuropsychological execution, such as sex, type of delivery, maternal age, gestational age and maternal educational level. Differences between countries disappeared and influence of culture was considerably reduced when standardised scores by country and sex were used. These results highlight the need for developing specific procedures to compare neuropsychological performance among children from different cultures to be used in multicentre studies.

Are All Breast-fed Infants Equal? Clustering Metabolomics Data to Identify Predictive Risk Clusters for Childhood Obesity.

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.

Does the fortified milk with high iron dose improve the neurodevelopment of healthy infants? Randomized controlled trial.

BACKGROUND: Since iron plays an important role in several physiological processes, its deficiency but also overload may harm the development of children. The aim was to assess the effect of iron-fortified milk on the iron biochemical status and the neurodevelopment of children at 12 months of age. METHODS: Randomized controlled trial conducted in 133 Spanish children, allocated in two groups to receive formula milk fortified with 1.2 or 0.4 mg/100 mL of iron between 6 and 12 months of age. Psychomotor (PDI) and Mental (MDI) Development Index were assessed by the Bayley Scales before and after the intervention. Maternal obstetrical and psychosocial variables were recorded. The biochemical iron status of children was measured and data about breastfeeding, anthropometry and infections during the first year of life were registered. RESULTS: Children fortified with 1.2 mg/100 mL of iron, compared with 0.4 mg/100 mL, showed higher serum ferritin (21.5 vs 19.1 µg/L) and lower percentage of both iron deficiency (1.1 to 5.9% vs 3.8 to 16.7%, respectively, from 6 to 12 months) and iron deficiency anemia (4.3 to 1.1% vs 0 to 4.2%, respectively, from 6 to 12 months) at the end of the intervention. No significant differences were found on neurodevelopment from 6 to 12 months between children who received high dose of Fe compared with those who received low dose. CONCLUSION: Despite differences on the iron status were observed, there were no effects on neurodevelopment of well-nourished children in a developed country after iron supplementation with doses within dietary recommendations. Follow-up studies are needed to test for long-term neurodevelopmental improvement. TRIAL REGISTRATION: Retrospectively registered in ClinicalTrials.gov with the ID: NCT02690675.

Unhealthy Dietary Patterns Established in Infancy Track to Mid-Childhood: The EU Childhood Obesity Project.

Background: Dietary habits established in infancy may persist into adulthood and determine long-term health. Objectives: The aims of this work were to describe dietary patterns, predictors of adherence to them, and their tracking from ages 1 to 8 y in European children. Methods: Three-day food diaries were prospectively collected at ages 1, 2, 3, 4, 5, 6 and 8 y. Foods were allocated to 1 of 29 food groups, which were included in exploratory factor analyses at each children's age. The tracking of patterns through childhood was assessed by an estimated general equation model. Results: At age 1 y (n = 633), 2 patterns were identified. One was labeled "core foods" (CORE), since it was positively loaded for vegetables, fish, olive oil, and white and red meat, and negatively loaded for ready-to-eat infant products, sugar, and confectioneries. The other was positively loaded for saturated spreads, sugar, fruit juices, and confectioneries, and negatively loaded for olive oil, fish, and cow milk; this was labeled as the "poor-quality fats and added sugars" (F&S) pattern. From ages 2 to 8 y, 3 patterns were repeatedly identified: CORE, F&S, and a "high protein sources" (PROT) pattern that was positively loaded for milk, flavored milks, fish, eggs, white and processed meat, chips, and olive oil, and negatively loaded for fresh fruits at almost all time points. Of those children in the highest quartiles of the CORE, F&S, and PROT patterns at 2 y, 45%, 72%, and 36%, respectively, remained in the highest quartile at 8 y [OR = 2.01 (1.08, 3.8), OR = 3.6 (1.5, 8.4) and OR = 0.80 (0.4,1.6), respectively; P = 0.510]. Conclusions: Dietary patterns are established between 1 and 2 y of age and track into mid-childhood. A dietary pattern characterized by added sugars, unhealthy fats, and poor consumption of fish and olive oil was the most stable throughout childhood. Further analyses will reveal whether those dietary patterns are associated with metabolic disease risk.

Bifidobacterium longum subsp infantis CECT7210-supplemented formula reduces diarrhea in healthy infants: a randomized controlled trial.

BackgroundIntestinal microbiota of breast-fed infants is plenty of beneficial bifidobacteria. We aimed to determine whether an infant formula supplemented with probiotic Bifidobacterium longum subsp. infantis CECT7210 (B. infantis IM1) is effective at reducing diarrhea incidence in healthy term infants.MethodsDouble-blinded, randomized, multicenter, controlled clinical trial, where formula-fed infants (<3 months) received an infant formula supplemented (Probiotic) or not (Control) with 107 cfu/g of B. infantis IM1 over 12 weeks. Diarrheas, growth, digestive symptoms, stool bifidobacteria, and microbiota were assessed.ResultsIn all, 97 (Control) and 93 (Probiotic) infants were randomized, and 78 (Control) and 73 (Probiotic) completed the 12 week-follow-up. In the overall study period, a median of 0.29±1.07 and 0.05±0.28 diarrhea events/infant was observed in the Control and Probiotic groups, respectively (P=0.059). This trend to less diarrhea episodes in the Probiotic group reached statistical significance at 8 weeks (0.12±0.47 vs. 0.0±0.0 events/infant, P=0.047). Constipation incidence was higher (odds ratio (OR) 2.67 (1.09-6.50)) and stool frequency lower (2.0±1.0 vs. 2.6±1.3 stools/day, P=0.038) in the Control group after 4 weeks. No differences were found at other time points nor in other digestive symptoms, growth, or formula intake.ConclusionA B. infantis IM1-supplemented infant formula may reduce diarrhea episodes, being safe, well tolerated, and associated with lower constipation prevalence.

Influence of Feeding Types during the First Months of Life on Calciuria Levels in Healthy Infants: A Secondary Analysis from a Randomized Clinical Trial.

BACKGROUND/AIMS: Dietary factors can modify calciuria. We aim to investigate urinary calcium excretion in healthy infants according to their protein. METHODS: Secondary data analysis from a randomized clinical trial where healthy term infants were randomized after birth to a higher (HP) or lower (LP) protein content formula that was consumed until age 1 year. A non-randomized group of breastfed (BF) infants was used for reference. Anthropometry, dietary intakes and calciuria (calcium/creatinine ratios) from spot urine samples were assessed at ages 3 and 6 months. At 6 months, the kidney volumes were assessed using ultrasonography, and the serum urea and creatinine levels were determined. RESULTS: BF infants showed the highest calciuria levels, followed by the HP and the LP groups (p < 0.001 for all comparisons). Either protein intakes or formula types modulated the calciuria in linear regression models adjusted for other influencing dietary factors. The usual cut-off values classified 37.8% (BF), 16.8% (HP) and 4.9% (LP) of the infants as hypercalciuric. CONCLUSIONS: Feeding types during the first months of life affect calciuria, with BF infants presenting the highest levels. We propose new cut-off values, based on feeding types, to prevent the overestimation in hypercalciuria diagnoses among BF infants.

BMI and recommended levels of physical activity in school children.

BACKGROUND: Physical activity (PA) and its health benefits are a continuous point of discussion. Recommendations for children's daily PA vary between guidelines. To better define the amount of PA necessary to prevent overweight and obesity in children, further research is needed. The present study investigates children's compliance to physical activity guidelines (PAGs) and the association between objectively measured PA and body mass index (BMI). METHODS: Participating children were 11 years old (n = 419) and part of the European CHOP trial, which was conducted in Germany, Belgium, Poland, Spain, Italy. At least 2 days of PA measurements were collected from each child using a SenseWear™ armband. BMI was calculated from children's height and weight. Thresholds of min·day-1 in PA needed to differentiate between normal and excess weight (overweight/obesity) were determined with Receiver Operator Characteristics (ROC) analysis. Additionally, adjusted linear and logistic regressions models were calculated for group differences and effects of a 5, 15 and 60 min·day-1 increases in PA on BMI. RESULTS: Median time spent in total PA was 462 min·day-1 (25th percentile; 75th percentile: 389; 534) and 75 min·day-1 (41; 115) in moderate to vigorous PA (MVPA). Girls spent 36 min·day-1 less in MVPA than boys and overweight/obese children 24 min·day-1 less than normal weight children (linear regression, p < 0.001). 63.2% of the children met PAGs of 60 min·day-1 in MVPA. The optimal threshold for min·day-1 in MVPA determined with ROC analysis was 46 min·day-1. Comparing 5, 15 and 60 min·day-1 increases in PA revealed that an additional 15 min·day-1 of vigorous PA had the same effect as 60 min·day-1 of MVPA. Sedentary time and light PA showed contrary associations to one another, with light PA being negatively and sedentary time being positively associated with excessive weight. CONCLUSIONS: Current PAGs are met by 2/3 of children and seem appropriate to prevent excess weight in children. An official recommendation of daily 15-20 min of vigorous PA and further reduction of sedentary time could help to fight youth overweight and thus be of potential public health importance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00338689 . Registered: June 19, 2006 (retrospectively registered).

The use of inulin-type fructans improves stool consistency in constipated children. A randomised clinical trial: pilot study.

BACKGROUND: Constipation is a common disorder in children. OBJECTIVE: The objective of this study is to assess the beneficial effects of a daily supplementation with Orafti® inulin-type fructans in 2-5 year old constipated children. METHODS: Double-blind, randomised, placebo-controlled parallel group trial where constipated children received two doses of 2 g Orafti® inulin-type fructans (OF:IN) or placebo (maltodextrin) for 6 weeks. Primary outcome was stool consistency. Secondary outcomes were stool frequency and gastrointestinal symptoms. RESULTS: Twenty-two children were included, 17 completed the study protocol (nine and eight for the control and the OF:IN group, respectively). Results showed that Orafti® inulin-type fructans supplemented children had softer stools (p = .003). The longitudinal analysis showed no significant changes in controls, whereas supplemented children increased their stool consistency from 2.2 to 2.6 on the modified Bristol scale for children (five items instead of seven) (p = .040). CONCLUSIONS: Prebiotic inulin-type fructans supplementation improves stool consistency in constipated 2-5-year old children. Clinicaltrials.gov, with number NCT02863848.

Higher protein intake increases cardiac function parameters in healthy children: metabolic programming by infant nutrition-secondary analysis from a clinical trial.

BACKGROUND: Protein intake may modulate cardiac structure and function in pathological conditions, but there is a lack of knowledge on potential effects in healthy infants. METHODS: Secondary analysis of an ongoing randomized clinical trial comparing two groups of infants receiving a higher (HP) or lower (LP) protein content formula in the first year of life, and compared with an observational group of breastfed (BF) infants. Growth and dietary intake were assessed periodically from birth to 2 y. Insulin-like growth factor 1 (IGF-1) axis parameters were analyzed at 6 mo in a blood sample. At 2 y, cardiac mass and function were assessed by echocardiography. RESULTS: HP infants (n = 50) showed a higher BMI z-score at 2 y compared with LP (n = 47) or BF (n = 44). Cardiac function parameters were increased in the HP group compared with the LP and were directly related to the protein intake during the first 6 mo of life. Moreover, there was an increase in free IGF-1 in the HP group at 6 mo. CONCLUSION: A moderate increase in protein supply during the first year of life is associated with higher cardiac function parameters at 2 y. IGF-1 axis modifications may, at least in part, underlie these effects.

Infant position in neonates receiving mechanical ventilation.

BACKGROUND: In patients of various ages undergoing mechanical ventilation (MV), it has been observed that positions other than the standard supine position, such as the prone position, may improve respiratory parameters. The benefits of these positions have not been clearly defined for critically ill newborns receiving MV.This is an update of a review first published in 2005 and last updated in 2013. OBJECTIVES: Primary objectiveTo assess the effects of different positioning of newborn infants receiving MV (supine vs prone, lateral decubitus or quarter turn from prone) in improving short-term respiratory outcomes. Secondary objectiveTo assess the effects of different positioning of newborn infants receiving MV on mortality and neuromotor and developmental outcomes over the long term, and on other complications of prematurity. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8), MEDLINE via PubMed (1966 to 22 August 2016), Embase (1980 to 22 August 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 22 August 2016). We also searched clinical trials databases, conference proceedings and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised and quasi-randomised clinical trials comparing different positions in newborns receiving mechanical ventilation. DATA COLLECTION AND ANALYSIS: Three unblinded review authors independently assessed trials for inclusion in the review and extracted study data. We used standard methodological procedures as expected by The Cochrane Collaboration and assessed the quality of the evidence using the GRADE approach. If the meta-analysis was not appropriate owing to substantial clinical heterogeneity between trials, we presented review findings in narrative format. MAIN RESULTS: We included in this review 19 trials involving 516 participants. Seven of the included studies (N = 222) had not been evaluated in the previous review. Investigators compared several positions: prone versus supine, prone alternant versus supine, prone versus lateral right, lateral right versus supine, lateral left versus supine, lateral alternant versus supine, lateral right versus lateral left, quarter turn from prone versus supine, quarter turn from prone versus prone and good lung dependent versus good lung uppermost.Apart from two studies that compared lateral alternant versus supine, one comparing lateral right versus supine and two comparing prone or prone alternant versus the supine position, all included studies had a cross-over design. In five studies, infants were ventilated with continuous positive airway pressure (CPAP); in the other studies, infants were treated with conventional ventilation (CV).Risks of bias did not differ substantially for different comparisons and outcomes. This update detects a moderate to high grade of inconsistency, similar to previous versions. However, for the analysed outcomes, the direction of effect was the same in all studies. Therefore, we consider that this inconsistency had little effect on the conclusions of the meta-analysis. When comparing prone versus supine position, we observed an increase in arterial oxygen tension (PO2) in the prone position (mean difference (MD) 5.49 mmHg, 95% confidence interval (CI) 2.92 to 8.05 mmHg; three trials; 116 participants; I2= 0). When percent haemoglobin oxygen saturation was measured with pulse oximetry (SpO2), improvement in the prone position was between 1.13% and 3.24% (typical effect based on nine trials with 154 participants; I2= 89%). The subgroup ventilated with CPAP (three trials; 59 participants) showed a trend towards improving SpO2 in the prone position compared with the supine position, although the mean difference (1.91%) was not significant (95% CI -1.14 to 4.97) and heterogeneity was extreme (I2= 95%).Sensitivity analyses restricted to studies with low risk of selection bias showed homogeneous results and verified a small but significant effect (MD 0.64, 95% CI 0.26 to 1.02; four trials; 92 participants; I2= 0).We also noted a slight improvement in the number of episodes of desaturation; it was not possible to establish whether this effect continued once the intervention was stopped. Investigators studied few adverse effects from the interventions in sufficient detail. Two studies analysed tracheal cultures of neonates after five days on MV, reporting lower bacterial colonisation in the alternating lateral position than in the supine posture. Other effects - positive or negative - cannot be excluded in light of the relatively small numbers of neonates studied. AUTHORS' CONCLUSIONS: This update of our last review in 2013 supports previous conclusions. Evidence of low to moderate quality favours the prone position for slightly improved oxygenation in neonates undergoing mechanical ventilation. However, we found no evidence to suggest that particular body positions during mechanical ventilation of the neonate are effective in producing sustained and clinically relevant improvement.