Gestational Diabetes Mellitus and its Effects on the Developing Cerebellum: A Narrative Review on Experimental Studies.

Diabetes mellitus during pregnancy is a common complication of gestation, but its effects on the offspring's development are poorly understood. Recently, some studies reported that gestational diabetes mellitus (GDM) impairs cerebellar development, and some genetic alterations have been described as consequences. Cerebellum, one of the hindbrain derived structures in the posterior cranial fossa, plays a crucial role in cognition and behavioral functions. In recent years, some surveys stated that gestational diabetes has adverse effects on the fetus's cerebellum. Disruption of cerebellar cortex morphogenesis, reduce the volume of the cerebellum, reduce the thickness of cerebellar cortex layers, and its neuronal cells and effects on the expression of synaptophysin, insulin, and insulin-like growth factor -1 receptors are some of the maternal diabetes effects on developing cerebellum. On other hand, GDM, as a neurotoxic agent, impaired cerebellar development and could be a cause for the behavioral, functional, and structural anomalies observed in pups of diabetic mothers. Based on the literature review, most studies have pointed out that administering insulin in patients with GDM decreased the cellular and molecular alterations that induced by GDM in the developing cerebellum. Undoubtedly, screening strategies for all pregnant women are necessary.

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.

Sensory Evaluation, Physico-Chemical Properties, and Aromatic Profile of Pasteurised Orange Juice with Resistant Maltodextrin.

The beneficial health effects of prebiotics have been demonstrated in numerous research papers. However, their incorporation into daily food remains unfamiliar to consumers. This work evaluates the effects of the addition of resistant maltodextrin (RMD) on the sensory attributes of pasteurised orange juice, together with the physico-chemical properties and the aromatic profile. RMD addition increased the sweetness and decreased the acidity and bitterness, resulting in a higher overall panellists' rating of orange juice. It also proportionally increased °Brix together with density and decreased acidity. Colour changes were registered with higher RMD concentrations. Orange pulp presence affected the volume particle size distribution analysis, while RMD addition did not have any effect. The aroma volatile compounds were also analysed. Pulp-added samples showed a higher quantity of alcohol and aldehydes, whereas pulp-free samples registered higher terpene and terpenoid values. Ketones and acids were also quantified. RMD had a moderate impact on volatile compound quantifications, with the orange pulp presence playing a much more decisive role. A correspondence analysis was also performed to relate instrumental and sensory determinations for all samples. This work proves that the addition of RMD to orange juice is technologically feasible while also achieving a good response at the sensory level.

Reproducibility and relative validity of a semi-quantitative food and beverage frequency questionnaire for Spanish children aged 3 to 11 years: the COME-Kids F&B-FQ.

A reliable food and beverage frequency questionnaire (F&B-FQ) to measure dietary intakes for children across Spain is currently unavailable. Thus, we designed and assessed the reproducibility and relative validity of a new F&B-FQ in 210 Spanish children aged 3-11 years. COME-Kids F&B-FQ contained 125 items to assess the usual diet intake in the past year among children. To explore the reproducibility, caregivers answered COME-Kids F&B-FQ twice over a 15-day period (± 1 week). To evaluate the relative validity, estimates from a third COME-Kids F&B-FQ administered at 1 year of follow-up were compared with the mean estimates from 3-day dietary records (3d-DR) collected at baseline, 6 months, and after 1 year of follow-up. Reproducibility and relative validity of the COME-Kids F&B-FQ in estimating food groups and nutrients were assessed using Pearson (r) and intra-class (ICC) correlation coefficients. We used the kappa index to evaluate the agreement in repeat administrations or with the 3d-DR. We used Bland-Altman plots to identify bias across levels of intake. A total of 195 children (105 boys, 90 girls) completed the study. The reproducibility of data estimated from COME-Kids F&B-FQ was substantial with mean r and ICC being 0.65 and 0.64 for food groups and 0.63 and 0.62 for nutrients, respectively. Validation assessments comparing the FFQ and 3d-DRs showed r = 0.36 and ICC = 0.30 for food groups and r = 0.29 and ICC = 0.24 for nutrients. The mean agreement for food group reproducibility and relative validity was 86% and 65%, respectively. These estimates were 85% for reproducibility and 64% for relative validity in the case of nutrients. For reproducibility and relative validity, the overall mean kappa index was 63% and 37% for all food groups and 52% and 27% for nutrients, respectively. Bland-Altman plots showed no specific bias relating to the level of intake of nutrients and several food groups. CONCLUSION: COME-Kids F&B-FQ showed substantial reproducibility and acceptable relative validity to assess food and beverage intake in Spanish children aged 3 to 11 years. Most children were correctly classified in relation to the intake of food groups and nutrients, and misclassification was unlikely with reference to 3d-DR. WHAT IS KNOWN: • The estimation of dietary intake in children is complex, especially in large cohorts. • The food frequency questionnaire is a well-recognized and the most frequently used method for assessing food consumption. WHAT IS NEW: • A new food and beverage frequency questionnaire including a beverage section and novel plant-based food items has been validated in Spanish children aged 3-11 years.

Association of the rs17782313, rs17773430 and rs34114122 Polymorphisms of/near MC4R Gene with Obesity-Related Biomarkers in a Spanish Pediatric Cohort.

Obesity is a multifactorial disease whose onset and development are shaped by the individual genetic background. The melanocortin 4 receptor gene (MC4R) is involved in the regulation of food intake and energy expenditure. Some of the single nucleotide polymorphisms (SNPs) of this gene are related to obesity and metabolic risk factors. The present study was undertaken to assess the relationship between three polymorphism SNPs, namely, rs17782313, rs17773430 and rs34114122, and obesity and metabolic risk factors. One hundred seventy-eight children with obesity aged between 7 and 16 years were studied to determine anthropometric variables and biochemical and inflammatory parameters. Our results highlight that metabolic risk factors, especially alterations in carbohydrate metabolism, were related to rs17782313. The presence of the minor C allele in the three variants (C-C-C) was significantly associated with anthropometric measures indicative of obesity, such as the body mass and fat mass indexes, and increased the values of insulinemia to 21.91 µIU/mL with respect to the wild type values. Our study suggests that the C-C-C haplotype of the SNPs rs17782313, rs17773430 and rs34114122 of the MC4R gene potentiates metabolic risk factors at early ages in children with obesity.

Circadian Disruption and Mental Health: The Chronotherapeutic Potential of Microbiome-Based and Dietary Strategies.

Mental illness is alarmingly on the rise, and circadian disruptions linked to a modern lifestyle may largely explain this trend. Impaired circadian rhythms are associated with mental disorders. The evening chronotype, which is linked to circadian misalignment, is a risk factor for severe psychiatric symptoms and psychiatric metabolic comorbidities. Resynchronization of circadian rhythms commonly improves psychiatric symptoms. Furthermore, evidence indicates that preventing circadian misalignment may help reduce the risk of psychiatric disorders and the impact of neuro-immuno-metabolic disturbances in psychiatry. The gut microbiota exhibits diurnal rhythmicity, as largely governed by meal timing, which regulates the host's circadian rhythms. Temporal circadian regulation of feeding has emerged as a promising chronotherapeutic strategy to prevent and/or help with the treatment of mental illnesses, largely through the modulation of gut microbiota. Here, we provide an overview of the link between circadian disruption and mental illness. We summarize the connection between gut microbiota and circadian rhythms, supporting the idea that gut microbiota modulation may aid in preventing circadian misalignment and in the resynchronization of disrupted circadian rhythms. We describe diurnal microbiome rhythmicity and its related factors, highlighting the role of meal timing. Lastly, we emphasize the necessity and rationale for further research to develop effective and safe microbiome and dietary strategies based on chrononutrition to combat mental illness.

Correlation of Anti-Tissue Transglutaminase Antibodies With the Mucosal Changes and IgA Status of Children With Celiac Disease.

OBJECTIVES: The objective of this study was to assess the association between serological markers and changes of the intestinal mucosa in children with celiac disease (CD). METHODS: Clinical data from CD patients under 15 years old were collected from the participating centers in an on-line multicenter nationwide observational Spanish registry called REPAC-2 (2011-2017). Correlation between anti-tissue transglutaminase antibodies (t-TGA) levels and other variables, including mucosal damage and clinical findings (symptoms, age, and gender), was assessed. RESULTS: A total of 2955 of 4838 patients had t-TGA and a small bowel biopsy (SBB) performed for CD diagnosis. A total of 1931 (66.2%) patients with normal IgA values had a Marsh 3b-c lesion and 1892 (64.9%) had t-TGA Immunoglobulin A (IgA) ≥ 10 times upper limit of normal (ULN). There is a statistically significant association between t-TGA IgA levels and the degree of mucosal damage ( P < 0.001), the higher the t-TGA IgA levels the more severe the mucosal damage. Those patients who reported symptoms had more severe mucosal damage ( P = 0.001). On the contrary, there was a negative association between age and changes of the intestinal mucosa ( P < 0.001). No association was found with gender. Regarding the IgA-deficient patients, 47.4% (18 cases) had t-TGA Immunoglobulin A (IgA) ≥ 10 times ULN and a Marsh 3b-c lesion was observed in 68.4% (26 patients). No statistical relation was found between t-TGA IgG levels and the changes of the intestinal mucosa, neither a relation with age, gender, or symptoms. CONCLUSIONS: There is a positive correlation between t-TGA IgA levels and the severity of changes of the intestinal mucosa. Such correlation was not found in IgA-deficient patients who had positive t-TGA IgG serology. The results in this group of patients support the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition recommendations about the need of performing a SBB in IgA-deficient individuals despite high t-TGA IgG levels.

Reduced Free Fatty Acid Receptor 4 Gene Expression is Associated With Extreme Obesity and Insulin Resistance in Children.

OBJECTIVES: Free fatty acid receptor 4 (FFAR4) is a G-protein-coupled membrane receptor highly expressed in macrophages that triggers anti-inflammatory effects and promotes insulin sensitization. We have previously found significant associations between the FFAR4 rs11187533 single nucleotide polymorphism (SNP) and various obesity comorbidity parameters. We aimed to verify the FFAR4 expression levels in children with obesity and the associated comorbidities. METHODS: Thirty-eight children with obesity were studied. Clinical and anthropometric evaluation was performed. A venous sample under fasting conditions was obtained. Biochemical study included parameters of metabolic risk. DNA was extracted and genotyped for the rs11187533 FFAR4 SNP. Real-time PCR technique was performed to investigate the gene expression. Relative FFAR4 mRNA levels were determined according to the 2-ΔΔCt method. RESULTS: Significant differences in FFAR4 expression levels between the CC and CT-TT genotypes of the rs11187533 FFAR4 SNP were observed (P = 0.034). The minor allele T presented higher levels of FFAR4 expression. We found that a loss of FFAR4 expression was associated with extreme obesity (P = 0.032). The lowest FFAR4 expression levels were observed in children who had higher insulin (P = 0.008) and homeostasis model assessment insulin resistance values (P = 0.012) and lower quantitative insulin-sensitivity check index (P = 0.033). CONCLUSIONS: The underexpression of FFAR4 was associated with extreme obesity and parameters indicative of obesity comorbidities in children. This under expression could be partially influenced by the presence of the C allele rs11187533 FFAR4 SNP.

Spanish National Registry of Paediatric Coeliac Disease: Changes in the Clinical Presentation in the 21st Century.

OBJECTIVES: Over the last several decades, there has been a tendency towards a predominance of less symptomatic forms of coeliac disease (CD) and an increase in the patient age at diagnosis. This study aimed to assess the clinical presentation and diagnostic process of paediatric CD in Spain. METHODS: A nationwide prospective, observational, multicentre registry of new paediatric CD cases was conducted from January 2011 to June 2017. The data regarding demographic variables, type of birth, breast-feeding history, family history of CD, symptoms, height and weight, associated conditions, serological markers, human leukocyte antigen (HLA) phenotype, and histopathological findings were collected. RESULTS: In total, 4838 cases (61% girls) from 73 centres were registered. The median age at diagnosis was 4 years. Gastrointestinal symptoms were detected in 71.4% of the patients, and diarrhoea was the most frequent symptom (45.9%). The most common clinical presentation was the classical form (65.1%) whereas 9.8% ofthe patients were asymptomatic. There was a trend towards an increase in the age at diagnosis, proportion of asymptomatic CD cases, and usage of anti-deamidated gliadin peptide antibodies and HLA typing for CD diagnosis. There was, however, a decreasing trend in the proportion of patients undergoing biopsies. Some of these significant trend changes may reflect the effects of the 2012 ESPGHAN diagnosis guidelines. CONCLUSIONS: Paediatric CD in Spain is evolving in the same direction as in the rest of Europe, although classical CD remains the most common presentation form, and the age at diagnosis remains relatively low.

Melatonin Levels in Children with Obesity Are Associated with Metabolic Risk and Inflammatory Parameters.

Melatonin, the hormone of circadian rhythm regulation, is involved in the modulation of mitochondrial activity through its antioxidant and anti-inflammatory properties. Alteration of circadian rhythms such as sleep is related to obesity and metabolic pathogenesis in adulthood, but studies during childhood are scarce. The present study investigated the association of melatonin with metabolic and inflammatory markers in children with (n = 113) and without obesity (n = 117). Melatonin was measured in saliva four and two hours before bedtime, and after one hour of sleep. Cardiometabolic factors, high sensitivity C-reactive protein, immune markers (monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, tumor necrosis α and interferon-γ), leptin and ghrelin were determined. Sleep duration was recorded by a questionnaire. The melatonin level at 1 h after sleep was found to be increased more than twofold in children with obesity (90.16 (57.16-129.16) pg/mL) compared to controls (29.82 (19.05-61.54) pg/mL, p < 0.001) and was related to fat mass (rho = 0.294, p < 0.001); melatonin levels at 1 h after sleep were inversely correlated with high-density lipoprotein cholesterol. Positive correlation was found with apolipoprotein B, adipokines, high sensitivity C-reactive protein, plasminogen activator inhibitor-1 and tumor necrosis factor-α. Shorter sleep duration and earlier waking times were recorded in children with obesity. In conclusion, melatonin in children with obesity appears to be involved in the global metabolic and inflammatory alteration of this condition.

Melatonin in Early Nutrition: Long-Term Effects on Cardiovascular System.

Breastfeeding protects against adverse cardiovascular outcomes in the long term. Melatonin is an active molecule that is present in the breast milk produced at night beginning in the first stages of lactation. This indoleamine appears to be a relevant contributor to the benefits of breast milk because it can affect infant health in several ways. The melatonin concentration in breast milk varies in a circadian pattern, making breast milk a chrononutrient. The consumption of melatonin can induce the first circadian stimulation in the infant's body at an age when his/her own circadian machinery is not functioning yet. This molecule is also a powerful antioxidant with the ability to act on infant cells directly as a scavenger and indirectly by lowering oxidant molecule production and enhancing the antioxidant capacity of the body. Melatonin also participates in regulating inflammation. Furthermore, melatonin can participate in shaping the gut microbiota composition, richness, and variation over time, also modulating which molecules are absorbed by the host. In all these ways, melatonin from breast milk influences weight gain in infants, limiting the development of obesity and comorbidities in the long term, and it can help shape the ideal cellular environment for the development of the infant's cardiovascular system.

Towards Tailored Gut Microbiome-Based and Dietary Interventions for Promoting the Development and Maintenance of a Healthy Brain.

Mental health is determined by a complex interplay between the Neurological Exposome and the Human Genome. Multiple genetic and non-genetic (exposome) factors interact early in life, modulating the risk of developing the most common complex neurodevelopmental disorders (NDDs), with potential long-term consequences on health. To date, the understating of the precise etiology underpinning these neurological alterations, and their clinical management pose a challenge. The crucial role played by diet and gut microbiota in brain development and functioning would indicate that modulating the gut-brain axis may help protect against the onset and progression of mental-health disorders. Some nutritional deficiencies and gut microbiota alterations have been linked to NDDs, suggesting their potential pathogenic implications. In addition, certain dietary interventions have emerged as promising alternatives or adjuvant strategies for improving the management of particular NDDs, at least in particular subsets of subjects. The gut microbiota can be a key to mediating the effects of other exposome factors such as diet on mental health, and ongoing research in Psychiatry and Neuropediatrics is developing Precision Nutrition Models to classify subjects according to a diet response prediction based on specific individual features, including microbiome signatures. Here, we review current scientific evidence for the impact of early life environmental factors, including diet, on gut microbiota and neuro-development, emphasizing the potential long-term consequences on health; and also summarize the state of the art regarding the mechanisms underlying diet and gut microbiota influence on the brain-gut axis. Furthermore, we describe the evidence supporting the key role played by gut microbiota, diet and nutrition in neurodevelopment, as well as the effectiveness of certain dietary and microbiome-based interventions aimed at preventing or treating NDDs. Finally, we emphasize the need for further research to gain greater insight into the complex interplay between diet, gut microbiome and brain development. Such knowledge would help towards achieving tailored integrative treatments, including personalized nutrition.

Effect of Adding Resistant Maltodextrin to Pasteurized Orange Juice on Bioactive Compounds and Their Bioaccessibility.

Resistant maltodextrin (RMD) is a water-soluble and fermentable functional fiber. RMD is a satiating prebiotic, reducer of glucose and triglycerides in the blood, and promoter of good gut health, and its addition to food is increasingly frequent. Therefore, it is necessary to study its potential effects on intrinsic bioactive compounds of food and their bioaccessibility. The aim of this study was to evaluate the effect of adding RMD on the bioactive compounds of pasteurized orange juice with and without pulp, and the bioaccessibility of such compounds. RMD was added at different concentrations: 0 (control sample), 2.5%, 5%, and 7.5%. Ascorbic acid (AA) and vitamin C were analyzed using HPLC, whereas total phenols, total carotenoids (TC), and antioxidant capacity were measured using spectrophotometry. After that, sample in vitro digestibility was assessed using the standardized static in vitro digestion method. The control orange juice with pulp presented significantly higher values of bioactive compounds and antioxidant capacity than the control orange juice without pulp (p < 0.05). RMD addition before the juice pasteurization process significantly protected all bioactive compounds, namely total phenols, TC, AA, and vitamin C, as well as the antioxidant capacity (AC) (p < 0.05). Moreover, this bioactive compound protective effect was higher when higher RMD concentrations were added. However, RMD addition improved phenols and vitamin C bioaccessibility but decreased TC and AA bioaccessibility. Therefore, the AC value of samples after gastrointestinal digestion was slightly decreased by RMD addition. Moreover, orange pulp presence decreased total phenols and TC bioaccessibility but increased AA and vitamin C bioaccessibility.

Vitamin D receptor gene ApaI and FokI polymorphisms and its association with inflammation and oxidative stress in vitamin D sufficient Caucasian Spanish children.

BACKGROUND: Vitamin D has gone from being just one vitamin to being an important prohormone with multiple effects on different tissue types. The mechanism of action of the active form or calcitriol is mediated by the intracellular vitamin D receptor (VDR). The interaction of the VDR with calcitriol modulates the expression of target genes involved in cell proliferation and cytokine production. Several studies have explored the effects of vitamin D deficiency in inflammatory disorders. Furthermore, some mutations in the VDR can affect its functionality. The focus of this study was to explore associations between VDR single nucleotide polymorphisms (SNPs) and markers of inflammation and oxidative stress in vitamin D sufficient children. METHODS: This is a cross-sectional study of a Caucasian Spanish population including 155 healthy children (87 males, 68 females) aged 10 to 14 years. FokI, ApaI and TaqI SNPs of the VDR gene were genotyped. Routine biochemistry, serum levels of interleukin-6, tumor necrosis factor-α, interferon-γ, 8-isoprostaglandin F2α and nitrates were determined. RESULTS: The homozygous major allele AA in the FokI SNP was associated with increased levels of high-density lipoprotein cholesterol in a recessive inheritance mode (P=0.025). The minor allele A of ApaI was significantly associated with decreased serum tumor necrosis factor-α and 8-isoprostaglandin F2α in an additive mode (P=0.016 and P=0.020 respectively). No significant associations were observed between the TaqI SNP and any of the parameters evaluated. Haplotype analysis confirmed the significance of the relationships between ApaI and FokI SNPs and parameters associated with inflammation and oxidative stress. CONCLUSIONS: Genetic variations of VDR are associated with subtle changes in metabolic, inflammatory and oxidative stress markers. These results may provide a better understanding of the relationships between vitamin D and these clinical parameters.

Impact of Resistant Maltodextrin Addition on the Physico-Chemical Properties in Pasteurised Orange Juice.

Resistant maltodextrin (RMD) is a water-soluble fibre that can be fermented in the colon and exert prebiotic effects. Therefore, its addition to food and beverage products could be beneficial from both technological and nutritional viewpoints. However, to date, most studies have focused on the stability of the prebiotic fibre rather than its impact in the original food matrices. Therefore, this work aimed to evaluate the addition of RMD on the physico-chemical properties of pasteurised orange juice (with and without pulp). °Brix, pH, acidity, particle size distribution, density, turbidity, rheology, and colour were measured in orange juices with increasing RMD concentrations (2.5, 5, and 7.5%). Control samples without RMD were also prepared. RMD added soluble solids to the orange juice, affecting the °Brix, density, turbidity, and rheology. Slight colour differences were observed, and lower citric acid content was achieved because of orange juice replacement with RMD. Differences in particle size distribution were exclusively because of pulp content. Further studies are needed to elucidate if potential consumers will appreciate such physico-chemical changes in organoleptic terms.

Melatonin Content of Human Milk: The Effect of Mode of Delivery.

Objective: Cesarean section rates are increasing in developed countries and could be performed as an emergency or elective procedure. Our research aim was to determine whether elective cesarean section influences the melatonin content, the main circadian hormone, in human milk. Methods: Twenty-one women after vaginal delivery and 18 women after elective cesarean section were included. Only healthy mothers with normal newborns exclusively breastfed were recruited. Two samples of human milk were collected for each woman at three stages of lactation: colostrum, transitional milk, and mature milk; at each stage, one daytime sample and another nighttime sample were obtained. In total, 228 milk samples were studied. The melatonin content was analyzed by enzyme-linked immunosorbent assay. Results: Melatonin rhythmicity with higher melatonin content at night was maintained at each of the three stages of lactation, regardless of the type of delivery. A higher melatonin content was found in daytime colostrum after cesarean section with respect to colostrum obtained from mothers after vaginal delivery (30.3 pg/mL versus 14.7 pg/mL, p = 0.020). Melatonin content decreased progressively throughout the course of lactation in both groups. This decrease was significant when comparing transitional milk to colostrum in the cesarean group, both in the daytime (p = 0.016) and nighttime samples (p = 0.048). Conclusions: Cesarean section is associated with an increase in daytime colostrum melatonin. No difference was observed in mature milk with respect to vaginal delivery. Melatonin values in human milk decrease during the first month of lactation and circadian rhythmicity was observed irrespective of the mode of delivery.

Leukocyte-Endothelium Interaction Is Associated with Fat Mass in Children.

OBJECTIVE: To study leukocyte-endothelium interaction, a measure of the initial phase of atheromatosis, in children with overweight or obesity. STUDY DESIGN: A prospective study was conducted in 77 children aged 7-16 years; 47 were children with overweight/obesity and 30 were normal weight. Polymorphonuclear neutrophils (PMNs) and peripheral blood mononuclear cells were isolated from venous blood samples and the interaction of leukocytes over a monolayer of human umbilical vein endothelial cells was analyzed using flow chamber microscopy. The variables studied included leukocyte rolling velocity, rolling flux, and adhesion to endothelial cells. These were compared between children with overweight/obesity and control children. Correlation between the measures of leukocyte-endothelium interaction and anthropometric and biochemical variables was evaluated. RESULTS: In comparison with normal weight children, the PMNs and peripheral blood mononuclear cells of the overweight/obesity group showed a reduction in rolling velocity (P = .000 and P = .001, respectively) and an increase in rolling flux (P = .001 and P = .004), and adhesion (P = .003 and P = .002). The homeostasis model of insulin resistance was correlated inversely with rolling velocity and positively with rolling flux in PMNs. C-reactive protein was correlated positively with rolling flux and adhesion in both types of leucocytes. Fat mass index was correlated with all measures of leukocyte-endothelial interaction and proved to be the main predictor of leukocyte adhesion in the multiple regression analysis (P = .001 for PMNs and P = .006 for peripheral blood mononuclear cells). CONCLUSIONS: Excess fat mass in children is related to the activation of the leukocyte-endothelium interaction, potentially contributing to the development of atherosclerosis.

The rs11187533 C>T Variant of the FFAR4 Gene Is Associated with Lower Levels of Fasting Glucose and Decreases in Markers of Liver Injury in Children with Obesity.

INTRODUCTION: Genetic factors can modulate the development of associated comorbidities in obesity. It has been shown that loss-of-function variants of the free fatty acid receptor 4 (FFAR4) gene negatively affect obesity comorbidities such as insulin resistance and fatty liver disease. OBJECTIVE: To test the relationships of metabolic factors in children with obesity with variants of the FFAR4 gene. METHODS: We performed an association study of 3 single nucleotide polymorphisms (SNPs) of FFAR4 (rs10882273 T>C, rs12243124 T>C, and rs11187533 C>T) covering the last intron and last exon of FFAR4 in a cohort of 203 children with obesity. Cardiometabolic factors were determined, including parameters related to insulin resistance, liver injury, and high-sensitivity C-reactive protein as an inflammatory marker. RESULTS: Significant genotype - phenotype interactions occurred between the rs11187533 SNP and glucose levels (p = 0.011). Moreover, we identified 2 marginally significant associations between this SNP and the hepatic enzymes alanine aminotransferase (p = 0.022) and gamma-glutamyltransferase (p = 0.015). The homozygous minor allele genotype (TT) was associated with a decrease in glucose levels. CONCLUSION: The homozygous minor allele genotype of the rs11187533 SNP might be protective against metabolic consequences accompanying obesity and could allow the identification of metabolically healthy obese individuals at early ages.

Depletion of Blautia Species in the Microbiota of Obese Children Relates to Intestinal Inflammation and Metabolic Phenotype Worsening.

Cross-sectional studies conducted with obese and control subjects have suggested associations between gut microbiota alterations and obesity, but the links with specific disease phenotypes and proofs of causality are still scarce. The present study aimed to profile the gut microbiota of lean and obese children with and without insulin resistance to characterize associations with specific obesity-related complications and understand the role played in metabolic inflammation. Through massive sequencing of 16S rRNA gene amplicons and data analysis using a novel permutation approach, we have detected decreased incidence of Blautia species, especially Blautia luti and B. wexlerae, in the gut microbiota of obese children, which was even more pronounced in cases with both obesity and insulin resistance. There was also a parallel increase in proinflammatory cytokines and chemokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and monocyte chemoattractant protein 1 [MCP-1]) in feces of obese children compared to those of lean ones. B. luti and B. wexlerae were also shown to exert an anti-inflammatory effect in peripheral blood mononuclear cell cultures in vitro, compared to non-obesity-associated species. We suggest that the depletion of B. luti and B. wexlerae species in the gut ecosystem may occur in cases of obesity and contribute to metabolic inflammation leading to insulin resistance.IMPORTANCE Child obesity constitutes a risk factor for developing insulin resistance which, if sustained, could lead to more severe conditions like type 2 diabetes (T2D) in adulthood. Our study identified previously unknown species whose depletion (Blautia luti and Blautia wexlerae) is associated with insulin resistance in obese individuals. Our results also indicate that these bacterial species might help to reduce inflammation causally linked to obesity-related complications. Childhood is considered a window of opportunity to tackle obesity. These new findings provide, therefore, valuable information for the future design of microbiota-based strategies for the early prevention of obesity-related complications.

[Validation and transcultural adaptation to spanish of the "Parental Supervision Attributes Profile Questionnaire"]. / Validación y adaptación transcultural al español del Parental Supervision Attributes Profile questionnaire: método de medición de la supervisión parental.

OBJECTIVE: Child accidents are the most important preventable cause of morbidity and mortality in pediatric age. The degree of parental supervision is a factor that can influence, among others, in these accidents. The aim of this study was to validate and cross-culturally adapt to Spanish the questionnaire Parental Supervision Attributes Profile Questionnaire (PSAPQ) as a method of measuring the degree of parental supervision. METHODS: Forward and back-translation methodology was applied using 4 bilingual spanish-english people to obtain version 1.0 of the questionnaire. Subsequently, the questionnaire was reviewed by a committee of experts, obtaining version 1.1, which was provided to 149 parents of children between 2-5 years old, randomly obtained, who attended consultation for the well child visits in several health centers in the province of Valencia. For the statistical study, the internal consistency was analyzed using Cronbach's α test and the test-retest reliability using Pearson correlations. RESULTS: A very good internal consistency was obtained, with Cronbach's α values greater than 0.7 in three of the four subscales that make up the test, with the remaining being 0.68. The reliability obtained was excellent, with values with Pearson correlations close to or higher than 0.7 for all subscales. CONCLUSIONS: The PSAPQ translated and validated into spanish shows very good psychometric results with respect to the original, so it can be said that an adequate instrument has been obtained to objectively measure one of the possible risk factors of child accidents.

OBJETIVO: Los accidentes infantiles son la causa prevenible más importante de morbi-mortalidad en edad pediátrica. El grado de supervisión parental es un factor que puede influir, entre otros, en su aparición. El objetivo de este estudio fue validar y adaptar transculturalmente al español el cuestionario Parental Supervision Attributes Profile Questionnaire (PSAPQ) como método de medida del grado de supervisión de los padres a sus hijos. METODOS: Se empleó una metodología de traducción/retrotraducción mediante 4 personas bilingües (españolinglés), obteniéndose la versión 1.0 del cuestionario. Posteriormente, fue revisada por un comité de expertos, obteniéndose la versión 1.1, que se proporcionó a 149 padres de niños de entre 2-5 años, reclutados de forma aleatoria, que acudían a las revisiones del programa de salud infantil de diversos centros de salud de la provincia de Valencia. En el estudio estadístico se analizó la consistencia interna mediante el test alfa de Cronbach y la fiabilidad test-retest mediante correlaciones de Pearson. RESULTADOS: Se obtuvo buena consistencia interna, con valores de alfa de Cronbach mayores de 0,7 en tres de las cuatro subescalas que forman el test. En la restante se consiguió un valor de 0,68. En cuanto a la fiabilidad, se obtuvieron correlaciones de Pearson cercanas o superiores a 0,7 para todas las subescalas. CONCLUSIONES: El PSAPQ traducido y validado al idioma español muestra muy buenos resultados psicométricos respecto al original, por lo que se puede afirmar que se ha obtenido un instrumento adecuado para medir objetivamente uno de los posibles factores de riesgo de accidentes infantiles.