Surgery for the treatment of obesity in children and adolescents

Background Child and adolescent overweight and obesity have increased globally, and are associated with significant short and long term health consequences. Objectives To assess the effects of surgical interventions for treating obesity in childhood and adolescence. Search methods We searched the Cochrane Library, MEDLINE, PubMed, EMBASE as well as LILACS, ICTRP Search Portal and ClinicalTrials.gov (all from database inception to March 2015). References of identified studies and systematic reviews were checked. No language restrictions were applied. Selection criteria We selected randomised controlled trials (RCTs) of surgical interventions for treating obesity in children and adolescents (age <18 years) with a minimum of six months follow-up. Interventions that specifically dealt with the treatment of eating disorders or type 2 diabetes, or included participants with a secondary or syndromic cause of obesity were excluded. Pregnant females were also excluded. Data collection and analysis Two review authors independently assessed risk of bias and extracted data. Where necessary authors were contacted for additional information. Main results We included one RCT (a total of 50 participants, 25 in both the intervention and comparator group). The intervention focused on laparoscopic adjustable gastric banding surgery, which was compared to a control group receiving a multi component lifestyle programme. The participating population consisted of Australian adolescents (a higher proportion of girls than boys) aged 14 to 18 years, with a mean age of 16.5 and 16.6 years in the gastric banding and lifestyle group, respectively which was conducted in a private hospital, receiving funding from the gastric banding manufacturer. The study authors were unable to blind participants, personnel and outcome assessors which may have resulted in a high risk of performance and detection bias. Attrition bias was noted as well. The study authors reported a mean reduction in weight of 34.6 kg (95% confidence interval (CI) 30.2 to 39.0) at two years, representing a change in body mass index (BMI) of 12.7 (95% CI 11.3 to 14.2) for the surgery intervention; and a mean reduction in weight of 3.0 kg (95% CI 2.1 to 8.1) representing a change in BMI of 1.3 (95% CI 0.4 to 2.9) for the lifestyle intervention. The differences between groups were statistically significant for all weight measures at 24 months (P <0.001). The overall quality of the evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was low. Adverse events were reported in 12/25 (48%) participants in the intervention group compared to 11/25 (44%) in the control group (low quality evidence). A total of 28% of the adolescents undergoing gastric banding required revisional surgery. No data were reported for all-cause mortality, behaviour change, participants views of the intervention and socioeconomic effects. At two years, the gastric banding group performed better than the lifestyle group in two of eight health-related quality of life concepts (very low quality evidence) as measured by the Child Health Questionnaire (physical functioning score (94 versus 78, community norm 95) and change in health score (4.4 versus 3.6, community norm 3.5)). Authors' conclusions Laparoscopic gastric banding led to greater body weight loss compared to a multi component lifestyle program in one small study with 50 patients. These results do not provide enough data to assess efficacy across populations from different countries, socioeconomic and ethnic backgrounds, who may respond differently. This systematic review highlights the lack of RCTs in this field. Future studies should assess the impact of the surgical procedure and post operative care to minimise adverse events, including the need for post operative adjustments and revisional surgery. Long-term follow-up is also critical to comprehensively assess the impact of surgery as participants enter adulthood

Liver Enzymes and the Development of Posttransplantation Diabetes Mellitus in Renal Transplant Recipients

BACKGROUND: Posttransplantation diabetes mellitus (PTDM) is common in renal transplant recipients (RTR), increasing the risk of graft failure, cardiovascular disease, and mortality. Early detection of a high risk for PTDM is warranted. Because liver function and liver fat are involved, we investigated whether serum liver markers are associated with future PTDM in RTR. METHODS: Between 2001 and 2003, 606 RTR with a functioning allograft beyond the first year after transplantation were included of which 500 participants (56% men; age, 50 ± 12 years) were free of diabetes at baseline and had liver enzyme values (1 missing) available. Serum concentrations of alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase were measured at baseline at 6.0 (6.2-11.5) years posttransplantation. PTDM cases were recorded until April 2012. RESULTS: During median follow-up for 9.6 years (interquartile range [IQR], 6.2-10.2) beyond baseline, 76 (15.2%) patients developed PTDM. Comparing the highest to the lower tertiles, higher liver enzyme activities were significantly related to incident PTDM for ALT (hazard ratio [HR], 2.22; IQR, 1.42-3.48), for GGT (HR, 2.93; IQR, 1.87-4.61), and for alkaline phosphatase (HR, 1.78; IQR, 1.13-2.80). The associations of ALT and GGT with development of PTDM were independent of potential confounders and risk factors, including age, sex, renal function, medication use, lifestyle factors, adiposity, presence of the metabolic syndrome, fasting glucose, HbA1c, proinsulin, and cytomegalovirus status. CONCLUSIONS: Markers for liver function and liver fat in the subclinical range are potential markers for future PTDM, independent of other known risk factors. This may allow for early detection and management of PTDM development

Estudio computacional del comportamiento como ácidos de Lewis de los haluros de Boro

[Abstract]: In this work we present a detailed computational study that aims to shed light on the anti-trend properties of the different boron halides in terms of their Lewis acidities (BF3 < BCl3 < BBr3). This trend in Lewis acidity is contrary to that expected considering the electronegativity of the halogen atoms. For this purpose we conducted a detailed investigation using density functional theory (DFT) calculations at the M062X/aug-cc-pVQZ level. The geometries and vibrational frequencies of the BX3 species and their adducts formed with NH3 were obtained and compared with the available experimental data. Subsequently, we carried out an energy analysis to gain information on the different energy contributions the lead to the observed trend. Finally, we performed a molecular orbital analysis. This study indicated that the increasing Lewis acidity on descending the halogens group is related to the stronger B-N bonds formed as the LUMO of the BX3 fragment approaches the energy of the HOMO of NH3.[Resumen]: En este trabajo se presenta un estudio computacional detallado que tiene como objetivo arrojar luz sobre la sorprendente tendencia en acidez de Lewis de los haluros de boro (BF3 < BCl3 < BBr3). Esta tendencia en acidez de Lewis es contraria a la esperada considerando la electronegatividad de los halógenos. Para este propósito se realizó una investigación minuciosa empleando la Teoría del Funcional de Densidad (DFT), con cálculos realizados al nivel M062X/aug-cc-pVQZ. Las geometrías moleculares y frecuencias vibracionales de las especies BX3 y sus aductos con NH3 fueron calculadas y comparadas con los valores experimentales. A continuación se realizó un análisis energético para evaluar como afectan las diferentes contribuciones energéticas a la tendencia observada. Finalmente se realizó un análisis de orbitales moleculares. Este estudio indicó que el aumento de la acidez de Lewis al descender en el grupo de los halógenos está relacionado con una mayor fortaleza de los enlaces B-N formados a medida que desciende la energía del LUMO del fragmento BX3 y ésta se aproxima a la del HOMO del NH3.Traballo fin de mestrado (UDC.CIE). Investigación química y química industrial. Curso 2017/201

Maternal alcohol consumption and offspring DNA methylation: Findings from six general population-based birth cohorts

Aim: Alcohol consumption during pregnancy is sometimes associated with adverse outcomes in offspring, potentially mediated by epigenetic modifications. We aimed to investigate genome-wide DNA methylation in cord blood of newborns exposed to alcohol in utero. Materials & methods: We meta-analyzed information from six population-based birth cohorts within the Pregnancy and Childhood Epigenetics consortium. Results: We found no strong evidence of association at either individual CpGs or across larger regions of the genome. Conclusion: Our findings suggest no association between maternal alcohol consumption and offspring cord blood DNA methylation. This is in stark contrast to the multiple strong associations previous studies have found for maternal smoking, which is similarly socially patterned. However, it is possible that a combination of a larger sample size, higher doses, different timings of exposure, exploration of a different tissue and a more global assessment of genomic DNA methylation might show evidence of association

Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation

Publisher Copyright: © 2022 The AuthorsBackground: Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits. Methods: We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5–10 years from 8 cohorts (n = 4268). Results: In newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p < 1.3 × 10−7) after adjusting for white blood cell proportions and batch. Most of those sites had lower methylation levels in males than in females. Of the differentially methylated CpG sites identified in newborn blood, 68% (31,727) met look-up level significance (p < 1.1 × 10−6) in older children and had methylation differences in the same direction. Conclusions: This is a large-scale meta-analysis examining sex differences in DNA methylation in newborns and older children. Expanding upon previous studies, we replicated previous findings and identified additional autosomal sites with sex-specific differences in DNA methylation. Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes.Peer reviewe

The LifeCycle Project-EU Child Cohort Network : a federated analysis infrastructure and harmonized data of more than 250,000 children and parents

Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It also provides a novel model for collaborative research in large research infrastructures with individual-level data. The LifeCycle Project will translate results from research using the EU Child Cohort Network into recommendations for targeted prevention strategies to improve health trajectories for current and future generations by optimizing their earliest phases of life.Peer reviewe

Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (P-Bonferroni <1.06 x 10(-7)). In additional analyses in 7,278 participants,Peer reviewe

Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

Background Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P <1.06 x 10(- 7), of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.Peer reviewe

DNA methylation and body mass index from birth to adolescence : meta-analyses of epigenome-wide association studies

Background DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits. Methods We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment. Results DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P <1.06 x 10(-7), with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth P-enrichment = 1; childhood P-enrichment = 2.00 x 10(-4); adolescence P-enrichment = 2.10 x 10(-7)). Conclusions There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.Peer reviewe