Birth Weight, Childhood and Young Adult Overweight, and the Risk of Coronary Heart Disease in Men.

BACKGROUND: Low birth weight is a known risk factor for adult coronary heart disease (CHD), but the additional effect of weight development during childhood and early adult life has not been studied. METHODS: We included 35 659 men born 1945 to 1961 from the population-based BMI Epidemiology Study Gothenburg, with data available on birthweight, BMI in childhood (8 years), and BMI in young adulthood (20 years). Information on CHD diagnoses was retrieved from national registers. We used Cox proportional hazards regression to estimate hazard ratios and 95% CIs for the risk of early and late CHD (before and after 58.4 years of age, respectively). RESULTS: During follow-up, a total of 3380 cases of CHD (fatal and nonfatal) were registered. Birth weight was inversely associated with the risk of both early (hazard ratio, 0.88 per SD increase [95% CI, 0.84-0.92]) and late (hazard ratio, 0.94 per SD increase [95% CI, 0.90-0.98]) CHD, independently of BMI at 8 years and BMI change during puberty. In a model including birth weight (below or above the median) together with overweight at 8 and 20 years, only birth weight and young adult overweight, but not overweight in childhood, were significantly associated with the risk of CHD. A birth weight below the median, followed by overweight at 20 years of age was associated with a more than doubled risk of early CHD (hazard ratio, 2.29 [95% CI, 1.86-2.81]), compared with the reference (birth weight above the median and normal weight at 20 years of age). This excess risk was even more pronounced for a birthweight below 2.5 kg. CONCLUSIONS: We demonstrate that low birth weight and young adult overweight are important developmental markers of risk for adult CHD. These findings motivate a life course perspective for prevention and risk assessment of adult CHD.

Impact of BMI and smoking in adolescence and at the start of pregnancy on birth weight.

BACKGROUND: Birth weight is an indicator of intra-uterine conditions but also a determinant for future health. The importance of preconception health for a healthy birth weight has been emphasized, but evidence is lacking on how modifiable factors in adolescence, such as body mass index (BMI) and smoking, affect future pregnancy outcome. We evaluated associations between BMI and smoking in adolescence and at the start of pregnancy and birth weight of the first-born child. METHODS: This longitudinal study included 1256 mothers, born 1962-1992, and their first-born children, born between 1982-2016. Self-reported questionnaire information on weight, height and smoking at age 19 was cross-linked with national register data obtained at the start of pregnancy and with the birth weights of the children. Univariable and multivariable linear regressions were performed to determine the impact of maternal factors at 19 years of age and at the start of the pregnancy respectively, and the importance of BMI status at these points of time for the birth weight of the first child. RESULTS: BMI and smoking at the start of the pregnancy displayed strong associations with birth weight in a multivariable analysis, BMI with a positive association of 14.9 g per BMI unit (95% CI 6.0; 23.8 p = 0.001) and smoking with a negative association of 180.5 g (95% CI -275.7; -85.4) p = 0.0002). Smoking and BMI at 19 years of age did not show this association. Maternal birth weight showed significant associations in models at both time-points. Becoming overweight between age 19 and the start of the pregnancy was associated with a significantly higher birth weight (144.6 (95% CI 70.7;218.5) p = 0.0002) compared to mothers with normal weight at both time points. CONCLUSIONS: Our findings indicate that the time period between adolescence and first pregnancy could be a window of opportunity for targeted health promotion to prevent intergenerational transmission of obesity.

Features of Childhood Growth, Lifestyle, and Environment Associated with a Cardiometabolic Risk Score in Young Adults.

INTRODUCTION: In young adults, metabolic syndrome (MS) is rare. To better assess the risks for future cardiovascular disease (CVD), a cardiometabolic score can be used, ranking the disease risk in each subject. The score is a continuous variable, summarizing the individual z-scores for waist circumference, blood pressure, blood levels of glucose, triglycerides, and high-density-lipoprotein cholesterol. Our main aim was to assess the association between early childhood growth and the cardiometabolic score in young adults. METHODS: Study participants were recruited among subjects in the longitudinal population-based GrowUp 1990 Gothenburg study. Those with information on weight and length at birth, as well as weight, height, waist circumference, and parental body mass index (BMI) at 10 years of age were invited to participate in a health survey at 18-20 years of age. Five hundred and thirteen young adults (female 51%) were included. Multivariable linear stepwise regression analysis was applied. RESULTS: The mean (standard deviation) BMI was 22.2 (3.26) in males and 21.3 (2.69) kg/m2 in females; the cardiometabolic score was 0.24 (3.12) and -0.22 (3.18), respectively. A statistically significantly higher score (p < 0.001) was seen in individuals with MS, as defined by IDF. After controlling for adult lifestyle features, the BMI z-score at 10 years of age was a significant risk factor in both sexes for an elevated cardiometabolic score in early adulthood with mean [standard error] beta 0.47 [0.19], p = 0.014 in males, and 0.82 [017], p < 0.0001 in females. In males, a high maternal BMI and low age at adiposity rebound and in females, high birth weight were also associated with a statistically significant risk. Additionally, contraceptive use in females was a risk factor for an elevated cardiometabolic score and in males, a high lifestyle-related index score showed a protective association with the cardiometabolic score. CONCLUSION: A high BMI z-score at 10 years of age is a risk factor for the cardiometabolic state in young adults, an outcome pointing to the preventive potential of monitoring BMI in 10-year-old schoolchildren. This finding must however be validated in a new large cohort. Moreover, in young adults in whom MS is rare, the cardiometabolic score seems to be a promising and more powerful tool to detect risks for CVD later in life than using MS categorization.

Longitudinal association of inflammatory markers with markers of glycaemia and insulin resistance in European children.

PURPOSE: Subclinical systemic inflammation may lead to development of type 2 diabetes, but there has been no investigation into its relationship with early progression of glycaemic deterioration and insulin resistance, especially in younger population. In this study we assessed longitudinal associations of pro- and anti-inflammatory markers with markers that evaluate glycaemia and insulin resistance. METHODS: This study includes 6537 initially nondiabetic children (mean age at baseline = 6.2 years) with repeated measurements from the IDEFICS/I.Family cohort study (mean follow-up = 5.3 years) from eight European countries. Markers of inflammation were used as independent variables and markers of glycaemia/insulin resistance as dependent variables. Associations were examined using two-level growth model. Models were adjusted for sex, age, major lifestyle, metabolic risk factors, early life markers, and other inflammatory markers in final model. RESULTS: Children with 6 years of follow-up showed that a one-unit increase in z-score of leptin level was associated with 0.38 (95% CI = 0.32 to 0.44) unit increase in HOMA-IR z-scores. Leptin continued to be associated with HOMA-IR even when analysis was limited to children with no overall obesity, no abdominal obesity, and low to normal triglyceride levels. An inverse association was observed between IL-15 and HOMA-IR (ß = -0.11, 95% CI = -0.15 to -0.07). CONCLUSIONS: IL-15 should be evaluated further in the prevention or treatment of prediabetes whereas leptin may prove to be useful in early detection of prediabetes via their association with markers of insulin resistance in European children.

Cross-Sectional and Longitudinal Associations Between Psychosocial Well-Being and Cardiometabolic Markers in European Children and Adolescents.

OBJECTIVE: Research examining aspects of positive mental health as potential predictors of cardiometabolic health in young populations is scarce. We investigated the associations between psychosocial well-being and waist circumference (WAIST), blood pressure (BP), the homeostasis model assessment for insulin resistance, triglycerides, and high-density lipoprotein cholesterol considering life-style factors as mediators. METHODS: Data of European children and adolescents participating in the baseline (2007/2008), first follow-up (FU1; 2009/2010) and second follow-up (FU2; 2013/2014) examinations of the IDEFICS/I.Family study were used (ncross-sectional = 6519; nlongitudinal = 1393). A psychosocial well-being score was calculated from 16 items on emotional well-being, self-esteem, and social relationships (0-48 points). Cardiometabolic markers were transformed to age- and sex-specific and, in case of BP, also height-specific z scores. Life-style factors included diet, physical activity, sleep, and electronic media use. Applying path analysis, we obtained unstandardized estimates of direct and indirect effects of well-being on cardiometabolic markers. RESULTS: Cross-sectionally, well-being score showed a negative direct and a negative indirect effect through life-style factors on WAIST z score (estimate per 4-point increase, -0.051 [p = .001] and -0.014 [p < .001], respectively). Longitudinally, positive changes in well-being score between baseline and FU1 and between FU1 and FU2, respectively, demonstrated negative indirect effects through life-style factorsFU2 on WAIST z scoreFU2. Both cross-sectionally and longitudinally, higher levels of well-being showed lowering indirect effects on homeostasis model assessment, BP, and triglyceride z scores and an increasing indirect effect on high-density lipoprotein cholesterol z score through both life-style factors and WAIST z score. CONCLUSIONS: These results supported our hypothesis that a healthier life-style may be one mechanism through which higher well-being is linked with lower abdominal obesity and fewer other cardiometabolic disorders in young populations. TRIAL REGISTRATION: Pan-European IDEFICS/I.Family children cohort, ISRCTN registry number: ISRCTN62310987 (http://www.isrctn.com/ISRCTN62310987).

The role of lifestyle and non-modifiable risk factors in the development of metabolic disturbances from childhood to adolescence.

BACKGROUND: The study aimed to identify the effects of lifestyle, C-reactive protein (CRP) and non-modifiable risk factors on metabolic disturbances in the transition from childhood to adolescence. METHODS: In 3889 children of the IDEFICS/I.Family cohort, latent transition analysis was applied to estimate probabilities of metabolic disturbances based on waist circumference, blood pressure, blood glucose, and lipids assessed at baseline and at 2- and 6-year follow-ups. Multivariate mixed-effects models were used to assess the age-dependent associations of lifestyle, non-modifiable risk factors and CRP, with the transformed probabilities of showing abdominal obesity, hypertension, dyslipidemia, or several metabolic disturbances (reference: being metabolically healthy). RESULTS: Higher maternal body mass index, familial hypertension as well as higher CRP z-score increased the risk for all four metabolic outcomes while low/medium parental education increased the risk of abdominal obesity and of showing several metabolic disturbances. Out of the lifestyle factors, the number of media in the bedroom, membership in a sports club, and well-being were associated with some of the outcomes. For instance, having at least one media in the bedroom increased the risk for showing several metabolic disturbances where the odds ratio (OR) markedly increased with age (1.30 [95% confidence interval 1.18; 1.43] at age 8; 1.18 [1.14; 1.23] for interaction with age; i.e., resulting in an OR of 1.30 × 1.18 = 1.53 at age 9 and so forth). Further, entering puberty at an early age was strongly associated with the risk of abdominal obesity (2.43 [1.60; 3.69] at age 8; 0.75 [0.69; 0.81] for interaction with age) and the risk of showing several metabolic disturbances (2.46 [1.53; 3.96] at age 8; 0.71 [0.65; 0.77] for interaction with age). CONCLUSIONS: Various factors influence the metabolic risk of children revealing the need for multifactorial interventions. Specifically, removing media from children's bedroom as well as membership in a sports club seem to be promising targets for prevention.

Common genetic variation in obesity, lipid transfer genes and risk of Metabolic Syndrome: Results from IDEFICS/I.Family study and meta-analysis.

As the prevalence of metabolic syndrome (MetS) in children and young adults is increasing, a better understanding of genetics that underlie MetS will provide critical insights into the origin of the disease. We examined associations of common genetic variants and repeated MetS score from early childhood to adolescence in a pan-European, prospective IDEFICS/I.Family cohort study with baseline survey and follow-up examinations after two and six years. We tested associations in 3067 children using a linear mixed model and confirmed the results with meta-analysis of identified SNPs. With a stringent Bonferroni adjustment for multiple comparisons we obtained significant associations(p < 1.4 × 10-4) for 5 SNPs, which were in high LD (r2 > 0.85) in the 16q12.2 non-coding intronic chromosomal region of FTO gene with strongest association observed for rs8050136 (effect size(ß) = 0.31, pWald = 1.52 × 10-5). We also observed a strong association of rs708272 in CETP with increased HDL (p = 5.63 × 10-40) and decreased TRG (p = 9.60 × 10-5) levels. These findings along with meta-analysis advance etiologic understanding of childhood MetS, highlighting that genetic predisposition to MetS is largely driven by genes of obesity and lipid metabolism. Inclusion of the associated genetic variants in polygenic scores for MetS may prove to be fundamental for identifying children and subsequently adults of the high-risk group to allow earlier targeted interventions.

Metabolic status in children and its transitions during childhood and adolescence-the IDEFICS/I.Family study.

BACKGROUND: This study aimed to investigate metabolic status in children and its transitions into adolescence. METHODS: The analysis was based on 6768 children who participated in the European IDEFICS/I.Family cohort (T0 2007/2008, T1 2009/2010 and/or T3 2013/2014; mean ages: 6.6, 8.4 and 12.0 years, respectively) and provided at least two measurements of waist circumference, blood pressure, blood glucose and lipids over time. Latent transition analysis was used to identify groups with similar metabolic status and to estimate transition probabilities. RESULTS: The best-fitting model identified five latent groups: (i) metabolically healthy (61.5%; probability for group membership at T0); (ii) abdominal obesity (15.9%); (iii) hypertension (7.0%); (iv) dyslipidaemia (9.0%); and (v) several metabolic syndrome (MetS) components (6.6%). The probability of metabolically healthy children at T0 remaining healthy at T1 was 86.6%; when transitioning from T1 to T3, it was 90.1%. Metabolically healthy children further had a 6.7% probability of developing abdominal obesity at T1. Children with abdominal obesity at T0 had an 18.5% probability of developing several metabolic syndrome (MetS) components at T1. The subgroup with dyslipidaemia at T0 had the highest chances of becoming metabolically healthy at T1 (32.4%) or at T3 (35.1%). Only a minor proportion of children showing several MetS components at T0 were classified as healthy at follow-up; 99.8% and 88.3% remained in the group with several disorders at T1 and T3, respectively. CONCLUSIONS: Our study identified five distinct metabolic statuses in children and adolescents. Although lipid disturbances seem to be quite reversible, abdominal obesity is likely to be followed by further metabolic disturbances.

Association of Infant Feeding Patterns with Taste Preferences in European Children and Adolescents: A Retrospective Latent Profile Analysis.

The aim was to investigate associations between the duration of infant feeding practices (FP) and taste preferences (TP) in European children and adolescents. A total of 5526 children (6-16 years old) of the I.Family study completed a Food and Beverage Preference Questionnaire to measure their preferences for sweet, fatty and bitter tastes. Mothers retrospectively reported the FPs duration in months: exclusive breastfeeding (EBF), exclusive formula milk feeding (EFMF), combined breastfeeding (BF&FMF) and the age at the introduction of complementary foods (CF). Using logistic regression analyses and latent class analysis (latent profiles of FP and CF were identified), we explored associations between profiles and TP, adjusting for various covariates, including the Healthy Diet Adherence Score (HDAS). A total of 48% of children had short durations of EBF (≤4 months) and BF&FMF (≤6 months) and were introduced to CF early (<6 months). No significant relationship was observed between the single FPs and TP, even when considering common profiles of FP. HDAS was inversely associated with sweet and fatty TP, but positively with bitter TP. Contrary to our hypotheses, we did not observe associations between FP and children's TP later in life. Further studies with higher FP variation and longitudinal design are needed to investigate the causal associations between infant FP and taste preferences later in life.

Sleep duration and blood pressure in children: Analysis of the pan-European IDEFICS cohort.

The present study aims to examine the cross-sectional and longitudinal association between self-reported nocturnal sleep duration, blood pressure, and hypertension in European children, aged 2-9.9 years, participating in the IDEFICS project. Blood pressure (BP) and the main anthropometric indices were measured according to standardized procedures. Childhood elevated BP and hypertension were defined according to the European Society of Hypertension Guidelines for children and adolescents. Parents reported lifestyle and socio-demographic data. Nocturnal sleep duration was assessed as part of a parental 24-h recall and categorized as follows: (a) ≤9 hours/night; (b) >9 hours to ≤10 hours/night; (c) >10 hours to ≤11 hours/night; and (d) >11 hours/night. A complete set of variables included in the present analysis was provided by 7974 participants (boys/girls = 4049/3925) at the baseline survey (T0). Of them, 5656 were re-examined 2 years later at follow-up (T1). Children reporting shorter sleep duration at T0 had significantly higher BP values (P for trend < 0.001) compared to those who slept more. Prospective analyses showed that shorter sleep duration at baseline predicted, over the 2-year follow-up, higher increases in systolic blood pressure and diastolic blood pressure, after adjustment for age, sex, country of origin, BMI z-score, parental education, physical activity, screen time, and T0 value of the examined outcome variables (P for trend < 0.001). Our findings reveal that shorter sleep duration is associated with higher BP in childhood, suggesting that sleep may be a potential risk factor for hypertension later in life.

Randomised study of children with obesity showed that whole body vibration reduced sclerostin.

AIM: New strategies are required to increase physical activity and improve metabolic profiles in children with obesity. We studied the effect of whole body vibration (WBV) on children with obesity on biochemical markers of energy and bone metabolism, anthropometric measurements, muscle parameters and calcaneal bone mineral density (BMD). METHODS: This was a randomised, prospective, controlled study of 30 children with a median age of 13 years (range 7-17) at Queen Silvia Children's Hospital, Gothenburg, Sweden, from 2013 to 2015. The target for the intervention group was to perform WBV three times a week for 12 weeks, and the study parameters were assessed at baseline and 12 weeks. RESULTS: The 16 in the WBV group achieved 51% of the planned activity, mainly at home, and were compared with 14 controls. Sclerostin, bone-specific alkaline phosphatase and carboxy-terminal collagen cross-links decreased in the WBV group (p < 0.05) and balance improved (p < 0.006), but osteocalcin and insulin remained unchanged. Anthropometric data, muscle strength and calcaneal BMD did not differ between the groups. CONCLUSION: WBV did not affect most of the clinical parameters in children with obesity, but the reduction in sclerostin implies that it had direct effects on osteocytes, which are key players in bone mechanotransduction.

Four-year outcome of randomly assigned lifestyle treatments in primary care of children with obesity.

AIM: To assess the four-year outcome in children with obesity randomised to one of two 12-month lifestyle treatment programmes in primary care. METHODS: At baseline, 64 children with obesity aged 8.0-13.0 years were randomised to a treatment programme managed either by a nurse, dietician and physiotherapist (n = 32) or by a nurse and dietician (n = 32). RESULTS: From baseline to follow-up, the mean body mass standard deviation score (BMISDS) had decreased by -0.50 [standard deviation (SD) 0.73], p = 0.002, in the nurse, dietician and physiotherapist group (n = 27), by -0.26 (SD 0.73), p = 0.057 in the other group (n = 29); adjusted mean difference was -0.22, 95% confidence interval -0.59; 0.16, p = 0.25. Changes in weight categories did not differ between the groups: both had a change from obesity to normal weight in 1 and to overweight in 6; in the physiotherapist group 1 case of severe obesity changed to obesity. The combined treatment groups (n = 56) had a mean reduction in BMISDS of -0.37 (SD 0.73) and an improved distribution in weight categories, p = 0.015. CONCLUSION: After four years, there was no difference in outcome between the treatment options. In the treatment groups combined the number of children with obesity and their adiposity measures were significantly lower.

Prospective associations between socioeconomically disadvantaged groups and metabolic syndrome risk in European children. Results from the IDEFICS study.

OBJECTIVE: Socioeconomic disadvantages during childhood are hypothesised to have negative implications for health. We aimed to investigate the association between socioeconomic disadvantages and children's total metabolic syndrome (MetS) score at baseline and follow-up and the extent to which socioeconomic disadvantages over time and the accumulation of these socioeconomic disadvantages can affect children's MetS risk. METHODS: The two-year longitudinal IDEFICS study included 2401 European children (aged 2.0-9.9) with complete information of the 16,229 participating at baseline. Sociodemographic variables, psychosocial factors and lifestyle were proxy-reported via questionnaires. Socioeconomically disadvantaged groups included children from families with low income, low education, migrant origin, unemployed parents, parents who lacked a social network, and from non-traditional families. MetS risk score was calculated as the sum of z-scores of waist circumference, blood pressure, lipids and insulin resistance. Linear mixed-effects models were used to study the association between social disadvantages and MetS risk. Models were adjusted for sex, age, well-being and lifestyle (fruit and vegetables consumption, physical activity, screen time). RESULTS: At both time points, children from low-income families (0.20 [0.03-0.37]); (ß estimate and 99% confidence interval), children from non-traditional families (0.14 [0.02-0.26]), children whose parents were unemployed (0.31 [0.05-0.57]) and children who accumulated >3 disadvantages (0.21 [0.04-0.37]) showed a higher MetS score compared to non-socioeconomically disadvantaged groups. CONCLUSION: Children from socioeconomically disadvantaged families are at high metabolic risk independently of diet, physical activity, sedentary behaviours and well-being. Interventions focusing on these socioeconomically disadvantaged groups should be developed to tackle health disparities.

Children's stress-related reports and stress biomarkers interact in their association with metabolic syndrome risk.

The purpose was to examine the cross-sectional associations of stress-related reports and stress biomarkers with metabolic syndrome (MetS) risk in children while also testing the interaction between stress biomarkers and stress reports. In 353 children (5-10 years old, 7.9% overweight/obese), MetS risk was measured by blood pressure, waist circumference, glucose homeostasis, triglycerides, and high-density cholesterol. Stress was measured by stress-related reports (events, emotions, and internalizing/externalizing problems) and two biomarkers: salivary cortisol (total-day and morning output) and heart rate variability (percentage of consecutive normal RR intervals differing more than 50 ms and low-to-high-frequency ratio). Cross-sectional regression analyses with z scored total MetS risk as outcome were adjusted for age, sex, and socio-economic status. Only internalizing problems were directly related to a higher MetS risk score (ß = 0.236). Cortisol and heart rate variability were significant moderators: High cortisol morning output resulted in a positive (unfavourable) report-MetS relationship (ß = 0.259-0.552), whereas low percentage of consecutive normal RR intervals differing more than 50 ms resulted in a negative (favourable) report-MetS relationship (ß = -0.298) and low low-to-high-frequency ratio in a positive (unfavourable) report-MetS relationship (ß = 0.478). In conclusion, stress can sometimes be a disadvantageous factor in metabolic health of otherwise healthy children. The cortisol biomarker seems relevant because metabolic risk was highest when stress-related reports were accompanied by high morning cortisol output.

Parental education and family income affect birthweight, early longitudinal growth and body mass index development differently.

AIM: This study investigated the effects of two parental socio-economic characteristics, education and income, on growth and risk of obesity in children from birth to 8 years of age. METHODS: Longitudinal growth data and national register-based information on socio-economic characteristics were available for 3,030 Swedish children. The development of body mass index (BMI) and height was compared in groups dichotomised by parental education and income. RESULTS: Low parental education was associated with a higher BMI from 4 years of age, independent of income, immigrant background, maternal BMI and smoking during pregnancy. Low family income was associated with a lower birthweight, but did not independently predict BMI development. At 8 years of age, children from less educated families had a three times higher risk of obesity, independent of parental income. Children whose parents had fewer years of education but high income had significantly higher height than all other children. CONCLUSION: Parental education protected against childhood obesity, even after adjusting for income and other important parental characteristics. Income-related differences in height, despite similar BMIs, raise questions about body composition and metabolic risk profiles. The dominant role of education underscores the value of health literacy initiatives for the parents of young children.

The role of neuromedin U in adiposity regulation. Haplotype analysis in European children from the IDEFICS Cohort.

BACKGROUND AND AIMS: Neuromedin U (NMU) is a hypothalamic neuropeptide with important roles in several metabolic processes, recently suggested as potential therapeutic target for obesity. We analysed the associations between NMU gene variants and haplotypes and body mass index (BMI) in a large sample of European children. METHODS AND RESULTS: From a large European multi-center study on childhood obesity, 4,528 children (2.0-9.9 years, mean age 6.0±1.8 SD; boys 52.2%) were randomly selected, stratifying by age, sex and country, and genotyped for tag single nucleotide polymorphisms (SNPs; rs6827359, T:C; rs12500837, T:C; rs9999653,C:T) of NMU gene, then haplotypes were inferred. Regression models were applied to estimate the associations between SNPs or haplotypes and BMI as well as other anthropometric measures. BMI was associated with all NMU SNPs (p<0.05). Among five haplotypes inferred, the haplotype carrying the minor alleles (CCT, frequency = 22.3%) was the only associated with lower BMI values (beta = -0.16, 95%CI:-0.28,-0.04, p = 0.006; z-score, beta = -0.08, 95%CI:-0.14,-0.01, p = 0.019) and decreased risk of overweight/obesity (OR = 0.81, 95%CI:0.68,0.97, p = 0.020) when compared to the most prevalent haplotype (codominant model). Similar significant associations were also observed using the same variables collected after two years' time (BMI, beta = -0.25, 95%CI:-0.41,-0.08, p = 0.004; z-score, beta = -0.10, 95%CI:-0.18,-0.03, p = 0.009; overweight/obesity OR = 0.81, 95%CI:0.66,0.99, p = 0.036). The association was age-dependent in girls (interaction between CCT haplotypes and age, p = 0.008), more evident between 7 and 9 years of age. The CCT haplotype was consistently associated with lower levels of fat mass, skinfold thickness, hip and arm circumferences both at T0 and at T1, after adjustment for multiple testing (FDR-adjusted p<0.05). CONCLUSIONS: This study shows an association between a NMU haplotype and anthropometric indices, mainly linked to fat mass, which appears to be age- and sex-specific in children. Genetic variations within or in linkage with this haplotype should be investigated to identify functional variants responsible for the observed phenotypic variation.

Laparoscopic Roux-en-Y gastric bypass in adolescents with severe obesity (AMOS): a prospective, 5-year, Swedish nationwide study.

BACKGROUND: Severe obesity in adolescence is associated with reduced life expectancy and impaired quality of life. Long-term benefits of conservative treatments in adolescents are known to be modest, whereas short-term outcomes of adolescent bariatric surgery are promising. We aimed to compare 5-year outcomes of adolescent surgical patients after Roux-en-Y gastric bypass with those of conservatively treated adolescents and of adults undergoing Roux-en-Y gastric bypass, in the Adolescent Morbid Obesity Surgery (AMOS) study. METHODS: We did a nationwide, prospective, non-randomised controlled study of adolescents (aged 13-18 years) with severe obesity undergoing Roux-en-Y gastric bypass at three specialised paediatric obesity treatment centres in Sweden. We compared clinical outcomes in adolescent surgical patients with those of matched adolescent controls undergoing conservative treatment and of adult controls undergoing Roux-en-Y gastric bypass. The primary outcome measure was change in BMI over 5 years. We used multilevel mixed-effect regression models to assess longitudinal changes. This trial is registered with ClinicalTrials.gov, number NCT00289705. FINDINGS: Between April, 2006, and May, 2009, 100 adolescents were recruited to the study, of whom 81 underwent Roux-en-Y gastric bypass (mean age 16·5 years [SD 1·2], bodyweight 132·8 kg [22·1], and BMI 45·5 kg/m2 [SD 6·1]). 80 matched adolescent controls and 81 matched adult controls were enrolled for comparison of outcomes. The change in bodyweight in adolescent surgical patients over 5 years was -36·8 kg (95% CI -40·9 to -32·8), resulting in a reduction in BMI of -13·1 kg/m2 (95% CI -14·5 to -11·8), although weight loss less than 10% occurred in nine (11%). Mean BMI rose in adolescent controls (3·3 kg/m2, 95% CI 1·1-4·8) over the 5-year study period, whereas the BMI change in adult controls was similar to that in adolescent surgical patients (mean change -12·3 kg/m2, 95% CI -13·7 to -10·9). Comorbidities and cardiovascular risk factors in adolescent surgical patients showed improvement over 5 years and compared favourably with those in adolescent controls. 20 (25%) of 81 adolescent surgical patients underwent additional abdominal surgery for complications of surgery or rapid weight loss and 58 (72%) showed some type of nutritional deficiency; health-care consumption (hospital attendances and admissions) was higher in adolescent surgical patients compared with adolescent controls. 20 (25%) of 81 adolescent controls underwent bariatric surgery during the 5-year follow-up. INTERPRETATION: Adolescents with severe obesity undergoing Roux-en-Y gastric bypass had substantial weight loss over 5 years, alongside improvements in comorbidities and risk factors. However, gastric bypass was associated with additional surgical interventions and nutritional deficiencies. Conventional non-surgical treatment was associated with weight gain and a quarter of patients had bariatric surgery within 5 years. FUNDING: Swedish Research Council; Swedish Governmental Agency for Innovation Systems; National Board of Health and Welfare; Swedish Heart and Lung Foundation; Swedish Childhood Diabetes Foundation; Swedish Order of Freemasons Children's Foundation; Stockholm County Council; Västra Götaland Region; Mrs Mary von Sydow Foundation; Stiftelsen Göteborgs Barnhus; Stiftelsen Allmänna Barnhuset; and the US National Institute of Diabetes, Digestive, and Kidney Diseases (National Institutes of Health).