Maternal obesity and gestational diabetes reprogram the methylome of offspring beyond birth by inducing epigenetic signatures in metabolic and developmental pathways.

BACKGROUND: Obesity is a negative chronic metabolic health condition that represents an additional risk for the development of multiple pathologies. Epidemiological studies have shown how maternal obesity or gestational diabetes mellitus during pregnancy constitute serious risk factors in relation to the appearance of cardiometabolic diseases in the offspring. Furthermore, epigenetic remodelling may help explain the molecular mechanisms that underlie these epidemiological findings. Thus, in this study we explored the DNA methylation landscape of children born to mothers with obesity and gestational diabetes during their first year of life. METHODS: We used Illumina Infinium MethylationEPIC BeadChip arrays to profile more than 770,000 genome-wide CpG sites in blood samples from a paediatric longitudinal cohort consisting of 26 children born to mothers who suffered from obesity or obesity with gestational diabetes mellitus during pregnancy and 13 healthy controls (measurements taken at 0, 6 and 12 month; total N = 90). We carried out cross-sectional and longitudinal analyses to derive DNA methylation alterations associated with developmental and pathology-related epigenomics. RESULTS: We identified abundant DNA methylation changes during child development from birth to 6 months and, to a lesser extent, up to 12 months of age. Using cross-sectional analyses, we discovered DNA methylation biomarkers maintained across the first year of life that could discriminate children born to mothers who suffered from obesity or obesity with gestational diabetes. Importantly, enrichment analyses suggested that these alterations constitute epigenetic signatures that affect genes and pathways involved in the metabolism of fatty acids, postnatal developmental processes and mitochondrial bioenergetics, such as CPT1B, SLC38A4, SLC35F3 and FN3K. Finally, we observed evidence of an interaction between developmental DNA methylation changes and maternal metabolic condition alterations. CONCLUSIONS: Our observations highlight the first six months of development as being the most crucial for epigenetic remodelling. Furthermore, our results support the existence of systemic intrauterine foetal programming linked to obesity and gestational diabetes that affects the childhood methylome beyond birth, which involves alterations related to metabolic pathways, and which may interact with ordinary postnatal development programmes.

Hypertension in children and adolescents.

Definition and management of arterial hypertension in children and adolescents are uncertain, due to different positions of current guidelines. The European Society of Cardiology task-force, constituted by Associations and Councils with interest in arterial hypertension, has reviewed current literature and evidence, to produce a Consensus Document focused on aspects of hypertension in the age range of 6-16 years, including definition, methods of measurement of blood pressure, clinical evaluation, assessment of hypertension-mediated target organ damage, evaluation of possible vascular, renal and hormonal causes, assessment and management of concomitant risk factors with specific attention for obesity, and anti-hypertensive strategies, especially focused on life-style modifications. The Consensus Panel also suggests aspects that should be studied with high priority, including generation of multi-ethnic sex, age and height specific European normative tables, implementation of randomized clinical trials on different diagnostic and therapeutic aspects, and long-term cohort studies to link with adult cardiovascular risk. Finally, suggestions for the successful implementation of the contents of the present Consensus document are also given.

Identifying poor cardiorespiratory fitness in overweight and obese children and adolescents by using heart rate variability analysis under resting conditions.

Background: Childhood obesity, including overweight, continues increasing worldwide affecting health expectancy, quality of life and healthcare expenditure. These subjects have higher probability of suffering or developing cardio metabolic risk factors. Recent studies have revealed cardiorespiratory fitness (CRF) as a valuable clinical parameter to identify these subjects and have even suggested cut-off values. However, evaluating CRF in overweight and obese youth can be difficult to implement, unfriendly and expensive.Objective: Develop a screening tool to identify high-risk subjects in a representative population of those attending overweight/obesity assessment programmes without prior intervention. It will be based on heart rate variability parameters, which has strong association with CRF and cardio metabolic risk factors.Methods: Sixty-three subjects, overweight and obese, between 9 and 17 years of age, and of both sexes were enrolled. None of them had secondary obesity syndromes and/or suffered from acute or chronic disease. Anthropometric parameters, electrocardiogram signal recording under resting conditions and cardiorespiratory fitness - evaluated by oxygen consumption and time elapsed of cardiopulmonary exercise test - were measured.Results: Significant differences in the sympathetic nervous system activity - assessed by heart rate variability analysis - are observed when grouping by overweight and obesity degree as well as by CRF (poor/normal). Body mass index, puberty and sympathetic nervous system activity are the significant variables of a logistic regression model develop to identify poor CRF individuals. Its accuracy reaches 92%.Conclusions: A screening tool based on heart rate variability and anthropometric parameters was developed to identify subjects with higher probability of suffering or developing cardio metabolic risk factors.

Blood cell transcript levels in 5-year-old children as potential markers of breastfeeding effects in those small for gestational age at birth.

BACKGROUND: Nutrition of the newborn during the early postnatal period seems to be of capital importance and there is clinical evidence showing the protective effect of breastfeeding compared with formula feeding on childhood obesity and its comorbidities. Infants born small for gestation age may be more sensitive to the type of feeding during lactation. Here, we aimed to analyze the impact of birth weight and the type of infant feeding on the expression levels in peripheral blood cells of selected candidate genes involved in energy homeostasis in 5-year-old children, to find out potential early biomarkers of metabolic programming effects during this period of metabolic plasticity. METHODS: Forty subjects were recruited at birth and divided in four groups according to birth weight (adequate or small for gestational age) and type of infant feeding (breastfeeding or formula feeding). They were followed from birth to the age of 5 years. RESULTS: At 5 years, no significant differences regarding anthropometric parameters were found between groups, and all children had normal biochemical values. Expression levels of UCP2 and MC4R in peripheral blood cells were lower and higher, respectively, in formula feeding children compared with breastfeeding ones (P = 0.002 and P = 0.064, two-way ANOVA). Differences were more marked and significant by Student's t test in small for gestation age children (P < 0.001 and P = 0.017, respectively). Transcript levels of FASN and FTO in peripheral blood cells were also different according to the type of infant feeding, but only in small for gestation age children. CONCLUSIONS: Altogether, these results suggest that small for gestation age infants are more sensitive to the type of feeding during lactation, and transcript levels of particular genes in peripheral blood cells, especially the MC4R/UCP2 mRNA ratio, may precisely reflect these effects in the absence of clear differences in phenotypic traits.

Longitudinal genome-wide DNA methylation analysis uncovers persistent early-life DNA methylation changes.

BACKGROUND: Early life is a period of drastic epigenetic remodeling in which the epigenome is especially sensitive to extrinsic and intrinsic influence. However, the epigenome-wide dynamics of the DNA methylation changes that occur during this period have not been sufficiently characterized in longitudinal studies. METHODS: To this end, we studied the DNA methylation status of more than 750,000 CpG sites using Illumina MethylationEPIC arrays on 33 paired blood samples from 11 subjects at birth and at 5 and 10 years of age, then characterized the chromatin context associated with these loci by integrating our data with histone, chromatin-state and enhancer-element external datasets, and, finally, validated our results through bisulfite pyrosequencing in two independent longitudinal cohorts of 18 additional subjects. RESULTS: We found abundant DNA methylation changes (110,726 CpG sites) during the first lustrum of life, while far fewer alterations were observed in the subsequent 5 years (460 CpG sites). However, our analysis revealed persistent DNA methylation changes at 240 CpG sites, indicating that there are genomic locations of considerable epigenetic change beyond immediate birth. The chromatin context of hypermethylation changes was associated with repressive genomic locations and genes with developmental and cell signaling functions, while hypomethylation changes were linked to enhancer regions and genes with immunological and mRNA and protein metabolism functions. Significantly, our results show that genes that suffer simultaneous hyper- and hypomethylation are functionally distinct from exclusively hyper- or hypomethylated genes, and that enhancer-associated methylation is different in hyper- and hypomethylation scenarios, with hypomethylation being more associated to epigenetic changes at blood tissue-specific enhancer elements. CONCLUSIONS: These data show that epigenetic remodeling is dramatically reduced after the first 5 years of life. However, there are certain loci which continue to manifest DNA methylation changes, pointing towards a possible functionality beyond early development. Furthermore, our results deepen the understanding of the genomic context associated to hyper- or hypomethylation alterations during time, suggesting that hypomethylation of blood tissue-specific enhancer elements could be of importance in the establishment of functional states in blood tissue during early-life.

Efficacy of a cognitive and behavioral treatment for childhood obesity supported by the ETIOBE web platform.

Recently, the prevalence of childhood obesity has increased alarmingly. Interventions combining eating habits, physical activity (PA), behavioral components, and family support have been shown to be effective, although variables such as self-efficacy beliefs and motivation seem to be important in achieving stable changes. Information and communication technologies (ICTs) can provide additional resources to traditional treatments. The objective is to analyze the efficacy of two treatments: a cognitive and behavioral treatment (CBT) focused on the promotion of healthy eating and PA habits, and this CBT intervention supported by a web platform (ETIOBE). Forty-seven obese children were randomized to these two conditions. Anthropometrical measures were evaluated before and after treatment and at follow-up. Self-efficacy and motivation questionnaires were filled out in the first and last intervention sessions. Mixed ANOVAs were performed for all variables. Simple mediation analyses were conducted to test whether the effect of condition on the post-intervention anthropometrical variable scores were mediated by self-efficacy. Results revealed that both treatments produced an improvement in the anthropometrical variables. CBT-E participants showed more PA self-efficacy as the treatment progressed and lower BMIz, lower fat mass, and higher lean mass. These results suggest that ICT help to improve the effects of childhood obesity interventions.

Home-exercise Childhood Obesity Intervention: A Randomized Clinical Trial Comparing Print Versus Web-based (Move It) Platforms.

PURPOSE: To compare the impact of adhering to a Mediterranean diet plus mixed physical exercise program (Move-It) implemented by means of printed instructions or via a web-platform (with or without e-mail support) on body composition, physical fitness, and blood pressure. DESIGN AND METHODS: Randomized clinical trial. Fifty-two overweight or obese Spanish children and adolescents were randomly assigned to the print-based (n = 18), Move-It (n = 18), or Move-It plus support (n = 16) intervention groups. Two-way mixed ANOVA tests were used to compare any changes between the groups in terms of percentage body fat, physical fitness (VO2peak), handgrip strength, and systolic and diastolic blood pressure. The measurements were taken before and after a three-month mixed-exercise (aerobic and resistance) and Mediterranean-diet program which was either implemented by means of printed instructions or via a web-platform (with or without e-mail support). RESULTS: No statistical differences were found between groups. However, the results highlighted significant improvements in body fat percentage metrics over time for all three groups (print-based: -1.8%, 95%CI -3.3% to -0.3%; Move-It: -1.8%, 95%CI -3.3% to -0.3%; Move-It plus support: -2.0%, 95%CI -3.7% to -0.4%, P < 0.05). We also observed a tendency towards improvement in the VO2peak, handgrip strength, and blood pressure variable values 10 min after the exercise-stress test in these three groups. CONCLUSIONS: The program improved the body composition, regardless of the way it is implemented. PRACTICE IMPLICATIONS: A mixed physical exercise program lasting for three months, combined with a Mediterranean diet, improves the body composition of children and adolescents with overweight/obesity.

Longitudinal study of DNA methylation during the first 5 years of life.

BACKGROUND: Early life epigenetic programming influences adult health outcomes. Moreover, DNA methylation levels have been found to change more rapidly during the first years of life. Our aim was the identification and characterization of the CpG sites that are modified with time during the first years of life. We hypothesize that these DNA methylation changes would lead to the detection of genes that might be epigenetically modulated by environmental factors during early childhood and which, if disturbed, might contribute to susceptibility to diseases later in life. METHODS: The study of the DNA methylation pattern of 485577 CpG sites was performed on 30 blood samples from 15 subjects, collected both at birth and at 5 years old, using Illumina(®) Infinium 450 k array. To identify differentially methylated CpG (dmCpG) sites, the methylation status of each probe was examined using linear models and the Empirical Bayes Moderated t test implemented in the limma package of R/Bioconductor. Surogate variable analysis was used to account for batch effects. RESULTS: DNA methylation levels significantly changed from birth to 5 years of age in 6641 CpG sites. Of these, 36.79 % were hypermethylated and were associated with genes related mainly to developmental ontology terms, while 63.21 % were hypomethylated probes and associated with genes related to immune function. CONCLUSIONS: Our results suggest that DNA methylation alterations with age during the first years of life might play a significant role in development and the regulation of leukocyte-specific functions. This supports the idea that blood leukocytes experience genome remodeling related to their interaction with environmental factors, underlining the importance of environmental exposures during the first years of life and suggesting that new strategies should be take into consideration for disease prevention.

Assessment of ten trace elements in umbilical cord blood and maternal blood: association with birth weight.

BACKGROUND: Trace elements are an essential nutritional component for humans and inadequate tissue-concentrations may have a significant effect on fetal size. OBJECTIVE: To measure ten trace elements in blood samples from mothers and their newborns, and assess their association with anthropometric characteristics at birth. The effects of other factors on fetal growth, such as biologic characteristics of the infant and mother, were analysed. METHODS: A cross-sectional study was conducted in the Hospital general, University of Valencia, Spain. Healthy pregnant women, and their full-term infants were selected (n = 54 paired samples). Infants were grouped according to birth weight: small for gestational age (SGA n = 11), appropriate (AGA n = 30), and large (LGA n = 13). Anthropometric and biologic characteristics of the infant and mother were recorded. Levels of ten essential elements: arsenic (As), barium (Ba), cobalt (Co), copper (Cu), chrome (Cr), iron (Fe), magnesium (Mg), manganese (Mn), selenium (Se) and zinc (Zn), in maternal and cord plasma samples were determined. Samples were obtained from the umbilical cord immediately after delivery and the samples of their mothers were drawn at 2-4 h after delivery. RESULTS: The analysis identified that cord blood Cu (p = 0.017) and maternal blood Ba and Mg (p = 0.027 and p = 0.002, respectively) concentrations were significantly higher among SGA infants compared to AGA and LGA infants. A multiple linear regression analysis showed that increased umbilical cord Cu concentration (adjusted ß -146.4 g, 95% CI -255 to -37.7; p = 0.009), maternal smoking during pregnancy (adjusted ß -483.8 g, 95% CI -811.7 to -155.9; p = 0.005), shorter gestational age (adjusted ß 350.1 g, 95% CI 244.5 to 455.8; p = 0.000), and female sex (adjusted ß -374 g, 95% CI -648 to -100; p = 0.009) were significantly associated with decreased birth weight. Maternal anaemia was positively associated with birth weight (adjusted ß 362 g, 95% CI 20.8 to 703.1; p = 0.038). No significant associations were found between maternal trace elements and birth weight in multivariate analysis. CONCLUSIONS: We did not observe significant associations of cord blood trace elements other than Cu and maternal trace elements with birth weight in the multivariate analyses.

DNA methylation patterns in newborns exposed to tobacco in utero.

BACKGROUND: Maternal smoking during pregnancy is a major risk factor for adverse health outcomes. The main objective of the study was to assess the impact of in utero tobacco exposure on DNA methylation in children born at term with appropriate weight at birth. METHODS: Twenty mother-newborn dyads, after uncomplicated pregnancies, in the absence of perinatal illness were included. All mothers were healthy with no cardiovascular risk factors, except for the associated risks among those mothers who smoked. Umbilical cord blood and maternal peripheral venous blood were collected and an epigenome-wide association study was performed using a 450 K epigenome-wide scan (Illumina Infinium HumanMethylation 450BeadChip) with adjustment to normalize the DNA methylation for data cell variability in whole blood. RESULTS: The maternal plasmatic cotinine levels ranged from 10.70-115.40 ng/ml in the exposed group to 0-0.59 ng/ml in the non-exposed group. After adjusting for multiple comparisons in 427102 probes, statistically significant differences for 31 CpG sites, associated to 25 genes were observed. There was a greater than expected proportion of statistically-significant loci located in CpG islands (Fisher's exact test, p = 0.029) and of those CpG islands, 90.3% exhibit higher methylation levels in the exposed group. The most striking and significant CpG site, cg05727225, is located in the chromosome 11p15.4, within the adrenomedullin gene. CONCLUSIONS: In utero tobacco exposure, even in the absence of fetal growth restriction, may alter the epigenome, contributing to global DNA hypomethylation. Therefore, DNA status can be used as a biomarker of prenatal insults. Considering the possibility to reverse epigenetic modifications, a window of opportunity exists to change the programmed chronic disease.

The kidney in obesity.

Body mass index has been found to be the second most important contributor to relative risk for developing end state renal disease (ESRD), after proteinuria. The impact of obesity on the kidney includes a wide spectrum, from characteristic pathologic lesions to increment in urinary albumin excretion (UAE) and proteinuria/or decrease in glomerular filtration rate (GFR). The cause of renal disease associated to obesity is not well understood, but two relevant elements emerge. The first is the presence of obesity-related glomerulopathy, and the second is the fat deposit in the kidney with impact on renal haemodynamics and intrarenal regulation. The mechanisms linking obesity and renal damage are complex and include haemodynamic changes, inflammation, oxidative stress, apoptosis, and finally renal scarring. The protection of kidney damage needs to combine weight reduction with the proper control of the cardiometabolic risk factors associated, hypertension, metabolic syndrome, diabetes and dyslipidaemia. The search for specific treatments merits future research.

Competitive active video games: Physiological and psychological responses in children and adolescents.

BACKGROUND: Recent strategies to reduce sedentary behaviour in children include replacing sedentary screen time for active video games. Active video game studies have focused principally on the metabolic consumption of a single player, with physiological and psychological responses of opponent-based multiplayer games to be further evaluated. OBJECTIVE: To determine whether adding a competitive component to playing active video games impacts physiological and psychological responses in players. METHODS: Sixty-two healthy Caucasian children and adolescents, nine to 14 years years of age, completed three conditions (8 min each) in random order: treadmill walking, and single and opponent-based Kinect active video games. Affect, arousal, rate of perceived exertion, heart rate and percentage of heart rate reserve were measured for each participant and condition. RESULTS: Kinect conditions revealed significantly higher heart rate, percentage of heart rate reserve, rate of perceived exertion and arousal when compared with treadmill walking (P<0.001). Opponent-based condition revealed lower values for the rate of perceived exertion (P=0.02) and higher affect (P=0.022) when compared with single play. CONCLUSION: Competitive active video games improved children's psychological responses (affect and rate of perceived exertion) compared with single play, providing a solution that may contribute toward improved adherence to physical activity.

HISTORIQUE: Parmi les récentes stratégies en vue de réduire les comportements sédentaires chez les enfants, soulignons le remplacement du temps d'écran sédentaire par des jeux vidéo actifs. Les études sur ce type de jeux ont surtout porté sur la consommation métabolique en mode solo. Les réponses physiologiques et psychologiques de jeux en mode multijoueur comportant des adversaires n'ont pas encore été évaluées. OBJECTIF: Déterminer si l'ajout d'un élément compétitif aux jeux vidéo actifs influe sur les réponses physiologiques et psychologiques chez les joueurs. MÉTHODOLOGIE: Soixante-deux enfants et adolescents blancs en bonne santé de neuf à 14 ans ont effectué trois conditionnements de huit minutes chacun, dans un ordre aléatoire : marche sur tapis roulant et jeux vidéo actifs Kinect en mode solo et multijoueur (Microsoft Corporation, États-Unis). Les chercheurs ont mesuré l'affect, l'éveil, le taux d'effort perçu, la fréquence cardiaque et le pourcentage de réserve de fréquence cardiaque de chaque participant et de chaque conditionnement. RÉSULTATS: Le conditionnement Kinect a suscité une augmentation significative de la fréquence cardiaque, du pourcentage de réserve de fréquence cardiaque, d'effort perçu et d'éveil par rapport à la marche sur tapis roulant (P<0,001). Le conditionnement contre un adversaire révélait des valeurs plus faibles de taux d'effort perçu (P=0,02) et un affect plus élevé (P=0,022) que le jeu en mode solo. CONCLUSION: Les jeux vidéo actifs compétitifs donnent de meilleures réponses psychologiques chez les enfants (affect et taux d'efforts perçu) que le jeu en mode solo. Cette solution pourrait contribuer à une meilleure adhérence à l'activité physique.

A holistic perspective of the comorbidities in childhood obesity.

Childhood obesity is associated with comorbidities that affect almost all body systems, including, among others, the endocrine, gastrointestinal, pulmonary, cardiovascular and musculoskeletal systems, as well as medical and surgical procedures that may be required due to different clinical situations. The objective of this article is to describe the classic and emerging comorbidities associated with obesity and the complications of procedures that involve invasive manoeuvres. Although some of the problems associated with obesity during childhood are widely known, such as musculoskeletal and cutaneous disorders or apnoea-hypopnoea syndrome, others, such as changes in kidney function, non-alcoholic fatty liver and cardiometabolic risk, have received less attention due to their insidious development, as they may not manifest until adulthood. In contrast, there is another group of comorbidities that may have a greater impact due to their frequency and consequences, which are psychosocial problems. Finally, in the context of invasive medico-surgical interventions, obesity can complicate airway management. The recognition of these pathologies in association with childhood obesity is of vital importance not only in childhood but also due to their ramifications in adulthood.

Association Between Elevated Body Mass Index and Cardiac Organ Damage in Children and Adolescents: Evidence and Mechanisms.

INTRODUCTION: Although a number of pathophysiological aspects of childhood obesity have been reported, few information are available on obesity-related cardiac organ damage. AIM: The present study was aimed at assessing the impact of anthropometric, blood pressure (BP) and metabolic variable on cardiac structure and function in youth. METHODS: In 78 subjects aged 5-16 years attending the outpatient clinic of cardiovascular risk (Valencia, Spain) anthropometric and metabolic variables, clinic and ambulatory BP and echocardiographic parameters were assessed. Subjects were also classified according to the presence of insulin resistance. RESULTS: Subjects mean age (± SD) amounted to 12.03 ± 2.4 years and males to 53.8%. Ten subjects were normoweight, 11 overweight, 39 obese, and 18 severely obese. No significant difference in office and ambulatory BP was detected among different bodyweight groups. A significant direct correlation was observed between left ventricular mass index (LVMI) and obesity markers [body mass index (BMI): r = 0.38, waist circumference (WC): r = 0.46, P < 0.04 for both]. Left ventricular hypertrophy, relative wall thickness and left atrial diameter were significantly related to BMI and WC. In contrast, office and ambulatory BP were unrelated to other variables, and differences in LVMI among different BP phenotypes were not significant. When partitioning the population by insulin resistance, LVMI, adjusted for confounders, was significantly greater in the insulin-resistant group. CONCLUSIONS: In children and adolescents characterized by different body weight patterns, weight factors "per se" and the related insulin resistance state appear to represent the main determinants of LVMI and left ventricular hypertrophy, independently on BP values and BP phenotypes.

Ambulatory blood pressure monitoring in children and adolescents: coming of age?

Over the last years, ambulatory blood pressure monitoring has been introduced into the pediatric population, contributing to a significant increase in the bulk of knowledge of crucial clinically relevant issues. Guidelines have established the currently known conditions where ambulatory blood pressure monitoring is useful and where it will provide additional information in children and adolescents. How common and important the intra-individual differences are within clinical and ambulatory blood pressure is the keystone to the use of ambulatory blood pressure monitoring as a diagnostic tool. By using not only office, but also ambulatory blood pressure, four possible situations arise. Two of these have values in agreement for normotension or hypertension. Two have values that are discrepant. The latter two are known as white coat and masked hypertension. The relationship with hypertension-induced organ damage, the prognostic value and the assessment of treatment goals are key issues of ambulatory blood pressure monitoring. In children, the accurate identification of hypertension at the earliest possible age would, therefore, give health-care providers the opportunity to initiate preventive measures, thereby reducing the chance of developing end-organ damage and its attendant morbidity and mortality.

Persistence and determinants of blood pressure phenotypes according to office and ambulatory blood pressure measurements in youth.

Ambulatory BP monitoring is increasingly used in children and adolescents, and the persistence of discrepant phenotypes, such as white coat or masked hypertension, is a relevant issue. The objective of this study was to assess the persistence of BP phenotypes over time and the factors related to their persistence. The study included 582 children and adolescents (9.4 ± 2.8 years of age) of both sexes (51% females) referred for routine health maintenance. Anthropometric parameters and office and 24-h ABPM measurements were obtained twice (interval 19.5 ± 6.9 months). BP classification and phenotypes were qualified using the 2016 ESH Guidelines. The correlation coefficient and kappa statistics were used to assess the persistence of phenotypes, and the related factors were evaluated using logistic regression. Based on both systolic and diastolic BP measurements, 91.6%, 16%, 17.2% and 13.7% of the subjects with true normotension, sustained HTN, white coat HTN and masked HTN, respectively, remained in the same category (overall agreement 74.2%, kappa 0.20). The multivariate model predicted the lack of persistence and correctly classified 90.3% of the subjects, with the pathological baseline BP phenotype (mainly masked HTN) being the independent variable that contributed most to the model. Excluding the phenotypes, the rest of the model explained 14% of the lack of persistence, and a high office SBP and high waist circumference were related to the lack of persistence. Furthermore, subjects who experienced an increase in their BMI z score and change in their BMI category were at risk of a lack of persistence. In conclusion, children, especially those with BP phenotypes different from true normotension, should be re-evaluated because a large percentage are likely to become normotensive.

Impact of Maternal Weight Gain on the Newborn Metabolome.

Pre-pregnancy obesity and excessive gestational weight gain (GWG) appear to affect birth weight and the offspring's risk of obesity and disease later in life. However, the identification of the mediators of this relationship, could be of clinical interest, taking into account the presence of other confounding factors, such as genetics and other shared influences. The aim of this study was to evaluate the metabolomic profiles of infants at birth (cord blood) and 6 and 12 months after birth to identify offspring metabolites associated with maternal GWG. Nuclear Magnetic Resonance (NMR) metabolic profiles were measured in 154 plasma samples from newborns (82 cord blood samples) and in 46 and 26 of these samples at 6 months and 12 months of age, respectively. The levels of relative abundance of 73 metabolomic parameters were determined in all the samples. We performed univariate and machine-learning analysis of the association between the metabolic levels and maternal weight gain adjusted for mother's age, Body Mass Index (BMI), diabetes, diet adherence and infant sex. Overall, our results showed differences, both at the univariate level and in the machine-learning models, between the offspring, according to the tertiles of maternal weight gain. Some of these differences were resolved at 6 and 12 months of age, whereas some others remained. Lactate and leucine were the metabolites with the strongest and longest association with maternal weight gain during pregnancy. Leucine, as well as other significant metabolites, have been associated in the past with metabolic wellness in both general and obese populations. Our results suggest that the metabolic changes associated to excessive GWG are present in children from early life.