Physical activity is prospectively associated with adolescent nonalcoholic fatty liver disease

Objectives: The aim of the present study was to assess whether objectively measured physical activity at mean ages 12 and 14 years are prospectively associated with ultrasound scan liver fat and stiffness (alanine aminotransferase, aspartate aminotransferase [AST], and [gamma]-glutamyl transferase [GGT]) assessed at mean age 17.8 years. Methods: Participants were from the Avon Longitudinal Study of Parents and Children. Total physical activity (counts per minute) and minutes of moderate to vigorous physical activity (MVPA) were measured using ActiGraph accelerometers at mean ages 12 and 14 years. Results: Greater total physical activity and MVPA at ages 12 and 14 years were associated with lower odds of liver fat and lower GGT levels at mean age 17.8 years, such as per 15-minute increase in daily MVPA at age 12 years, the confounder adjusted odds ratio of liver fat was 0.47 (95% confidence interval [CI] 0.27–0.84). Associations attenuated after additional adjustment for fat mass as a potential confounder (eg, per 15-minute increase in daily MVPA at age 12 years, the odds ratio of liver fat attenuated to 0.65 [95% CI 0.35–1.21]) or a potential mediator (eg, per 15-minute increase in daily MVPA at age 12 years the odds ratio of liver fat attenuated to 0.59 [95% CI 0.32–1.09]). Results did not further attenuate after additional adjustment for insulin resistance. There was some evidence that greater total physical activity and MVPA at age 12 years were associated with the higher AST levels. Conclusions: Adolescents who were more active in childhood have lower odds of fatty liver and lower GGT levels. These findings are likely to be, at least in part, explained by adiposity

Association of maternal diabetes/glycosuria and pre-pregnancy body mass index with offspring indicators of non-alcoholic fatty liver disease

Background: Little is known about early life determinants of non-alcoholic fatty liver disease (NAFLD). We examined associations of maternal pregnancy diabetes/glycosuria and pre-pregnancy body mass index (BMI) with offspring markers of NAFLD and liver pathology and examined mediation by birthweight and concurrent offspring adiposity. Methods: We used data from a UK prospective pregnancy cohort. Offspring underwent abdominal ultrasonography (USS) at mean age 17.8 years. Outcomes included USS-assessed fatty liver, estimated liver volume and shear velocity, a variant of elastography (a marker of liver fibrosis) (N = 1 215) and blood-based markers of liver pathology [alanine amino transferase, aspartate amino transferase, gamma- glutamyltransferase and haptoglobin] (N = 2 359). Results: 2.1 % (N = 25) of participants had USS-assessed fatty liver [maternal diabetes/glycosuria (N = 7) and no diabetes/glycosuria (N = 18)]. Maternal diabetes/glycosuria was associated with greater odds of offspring USS fatty liver in confounder adjusted models [adjusted odds ratio (aOR) 6.74 (95 % confidence interval (CI) 2.47, 18.40)] and higher shear velocity [adjusted ratio of geometric mean (aRGM):1.10 (95 % CI 1.05, 1.15)]. These associations were not mediated by offspring birthweight or concurrent adiposity. Maternal diabetes/glycosuria was not associated with liver volume or blood-based outcomes. Greater maternal pre-pregnancy BMI was associated with greater odds of offspring USS fatty liver [aOR 2.72 (95 % CI: 1.20, 6.15)], higher liver volume [aRGM 1.03 (95 % CI 1.00, 1.07)] and shear velocity [aRGM1.03 (95 % CI: 1.01, 1.06)] in confounder adjusted models. These associations were largely mediated by offspring adiposity. Maternal pre-pregnancy BMI was not consistently associated with blood-based outcomes. Conclusions: Results suggest that maternal pregnancy diabetes/glycosuria is associated with offspring NAFLD through mechanisms other than offspring’s own adiposity

Hypertensive Disorders of Pregnany and Offspring Cardiac Structure and Function in Adolescence

Background-Fetal exposure to preeclampsia is associated with higher blood pressure and later risk of stroke. We aimed to investigate the associations of maternal preeclampsia, gestational hypertension, and maternal blood pressure change in pregnancy with offspring cardiac structure and function in adolescence. Methods and Results-Using data from a prospective birth cohort study, we included offspring who underwent echocardiography (mean age, 17.7 years; SD, 0.3; N=1592). We examined whether hypertensive disorders of pregnancy were associated with offspring cardiac structure and systolic/diastolic function using linear regression. Using multilevel linear spline models (measurement occasions within women), we also investigated whether rate of maternal systolic/diastolic blood pressure change during pregnancy (weeks 8-18, 18-30, 30-36, and 36 or more) were associated with offspring outcomes. Main models were typically adjusted for maternal age, offspring age and sex, prepregnancy body mass index, parity, glycosuria/diabetes mellitus, education, and maternal smoking. Exposure to maternal preeclampsia (0.025; 95% CI, 0.008-0.043) and gestational hypertension (0.010; 0.002-0.017) were associated with greater relative wall thickness. Furthermore, preeclampsia was also associated with a smaller left ventricular end-diastolic volume (-9.0 mL; -15 to -3.1). No associations were found between hypertensive disorders of pregnancy and offspring cardiac function. Positive rate of maternal systolic blood pressure change during weeks 8 to 18 was associated with greater offspring left ventricular end-diastolic volume, left ventricular mass indexed to height2.7, and E/A. Conclusions-Adolescent offspring exposed to maternal preeclampsia had greater relative wall thickness and reduced left ventricular end-diastolic volume, which could be early signs of concentric remodeling and affect future cardiac function as well as risk of cardiovascular disease

Childhood energy intake is associated with nonalcoholic fatty liver disease in adolescents

Background: Greater adiposity is an important risk factor for nonalcoholic fatty liver disease (NAFLD). Thus, it is likely that dietary intake is involved in the development of the disease. Prospective studies assessing the relation between childhood dietary intake and risk of NAFLD are lacking. Objective: This study was designed to explore associations between energy, carbohydrate, sugar, starch, protein, monounsaturated fat, polyunsaturated fat, saturated fat, and total fat intake by youth at ages 3, 7, and 13 y and subsequent (mean age: 17.8 y) ultrasound scan (USS)–measured liver fat and stiffness and serum alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltransferase. We assessed whether observed associations were mediated through fat mass at the time of outcome assessment. Methods: Participants were from the Avon Longitudinal Study of Parents and Children. Trajectories of energy and macronutrient intake from ages 3–13 y were obtained with linear-spline multilevel models. Linear and logistic regression models examined whether energy intake and absolute and energy-adjusted macronutrient intake at ages 3, 7, and 13 y were associated with liver outcomes. Results: Energy intake at all ages was positively associated with liver outcomes; for example, the odds of having a USS-measured liver fat per 100 kcal increase in energy intake at age 3 y were 1.79 (95% CI: 1.14, 2.79). Associations between absolute macronutrient intake and liver outcomes were inconsistent and attenuated to the null after adjustment for total energy intake. The majority of associations attenuated to the null after adjustment for fat mass at the time liver outcomes were assessed. Conclusion: Higher childhood and early adolescent energy intake is associated with greater NAFLD risk, and the macronutrients from which energy intake is derived are less important. These associations appear to be mediated, at least in part, by fat mass at the time of outcome assessment

Changes in ponderal index and body mass index across childhood and their associations with fat mass and cardiovascular risk factors at age 15

Background: Little is known about whether associations between childhood adiposity and later adverse cardiovascular health outcomes are driven by tracking of overweight from childhood to adulthood and/or by vascular and metabolic changes from childhood overweight that persist into adulthood. Our objective is to characterise associations between trajectories of adiposity across childhood and a wide range of cardiovascular risk factors measured in adolescence, and explore the extent to which these are mediated by fat mass at age 15. Methods and Findings: Using data from the Avon Longitudinal Study of Parents and Children, we estimated individual trajectories of ponderal index (PI) from 0-2 years and BMI from 2-10 years using random-effects linear spline models (N = 4601). We explored associations between PI/BMI trajectories and DXA-determined total-body fat-mass and cardiovascular risk factors at 15 years (systolic and diastolic blood pressure, fasting LDL-and HDL-cholesterol, triglycerides, C-reactive protein, glucose, insulin) with and without adjustment for confounders. Changes in PI/BMI during all periods of infancy and childhood were associated with greater DXA-determined fat-mass at age 15. BMI changes in childhood, but not PI changes from 0-2 years, were associated with most cardiovascular risk factors in adolescence; associations tended to be strongest for BMI changes in later childhood (ages 8.5-10), and were largely mediated by fat mass at age 15. Conclusion: Changes in PI/BMI from 0-10 years were associated with greater fat-mass at age 15. Greater increases in BMI from age 8.5-10 years are most strongly associated with cardiovascular risk factors at age 15, with much of these associations mediated by fat-mass at this age. We found little evidence supporting previous reports that rapid PI changes in infancy are associated with future cardiovascular risk. This study suggests that associations between early overweight and subsequent adverse cardiovascular health are largely due to overweight children tending to remain overweight

DNA methylation and body mass index:investigating identified methylation sites at HIF3A in a causal framework

Multiple differentially methylated sites and regions associated with adiposity have now been identified in large-scale cross-sectional studies. We tested for replication of associations between previously identified CpG sites at HIF3A and adiposity in ∼1,000 mother-offspring pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC). Availability of methylation and adiposity measures at multiple time points, as well as genetic data, allowed us to assess the temporal associations between adiposity and methylation and to make inferences regarding causality and directionality. Overall, our results were discordant with those expected if HIF3A methylation has a causal effect on BMI and provided more evidence for causality in the reverse direction (i.e., an effect of BMI on HIF3A methylation). These results are based on robust evidence from longitudinal analyses and were also partially supported by Mendelian randomization analysis, although this latter analysis was underpowered to detect a causal effect of BMI on HIF3A methylation. Our results also highlight an apparent long-lasting intergenerational influence of maternal BMI on offspring methylation at this locus, which may confound associations between own adiposity and HIF3A methylation. Further work is required to replicate and uncover the mechanisms underlying the direct and intergenerational effect of adiposity on DNA methylation.Rebecca C. Richmond, Gemma C. Sharp, Mary E. Ward, Abigail Fraser, Oliver Lyttleton, Wendy L. McArdle, Susan M. Ring, Tom R. Gaunt, Debbie A. Lawlor, George Davey Smith, and Caroline L. Relto

Real Lives; Real Difference: Service User and Carer Involvement in Professional Education. Conference Summary Report

First paragraph: On the 4th of June 2013, eight Scottish universities involved in the Scottish Inter-University Social Work Service User and Carers' Network, supported by the Scottish Social Services Council (SSSC) and the Institute for Research and Innovation in Social Services (IRISS), collaborated to produce the first national service user and carer conference aimed at highlighting the importance of involving people who have experience of using Social Work and/or health services in the education of Social Workers and other professionals. The day was deemed "interesting, informative and successful" and involved approximately 45 people delivering presentations and workshops to just over 100 conference delegates. The one-day conference included a keynote speaker and a research presentation delivered by leading academics in Social Work education, poetry recitations delivered by a Social Work service user and workshops delivered by Social Work and Nursing academics, Service Users and carers and social work students

Anti-müllerian hormone is not associated with cardiometabolic risk factors in adolescent females

<p>Objectives: Epidemiological evidence for associations of Anti-Müllerian hormone (AMH) with cardiometabolic risk factors is lacking. Existing evidence comes from small studies in select adult populations, and findings are conflicting. We aimed to assess whether AMH is associated with cardiometabolic risk factors in a general population of adolescent females.</p> <p>Methods: AMH, fasting insulin, glucose, HDLc, LDLc, triglycerides and C-reactive protein (CRP) were measured at a mean age 15.5 years in 1,308 female participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Multivariable linear regression was used to examine associations of AMH with these cardiometabolic outcomes.</p> <p>Results: AMH values ranged from 0.16–35.84 ng/ml and median AMH was 3.57 ng/ml (IQR: 2.41, 5.49). For females classified as post-pubertal (n = 848) at the time of assessment median (IQR) AMH was 3.81 ng/ml (2.55, 5.82) compared with 3.25 ng/ml (2.23, 5.05) in those classed as early pubertal (n = 460, P≤0.001). After adjusting for birth weight, gestational age, pubertal stage, age, ethnicity, socioeconomic position, adiposity and use of hormonal contraceptives, there were no associations with any of the cardiometabolic outcomes. For example fasting insulin changed by 0% per doubling of AMH (95%CI: −3%,+2%) p = 0.70, with identical results if HOMA-IR was used. Results were similar after additional adjustment for smoking, physical activity and age at menarche, after exclusion of 3% of females with the highest AMH values, after excluding those that had not started menarche and after excluding those using hormonal contraceptives.</p> <p>Conclusion: Our results suggest that in healthy adolescent females, AMH is not associated with cardiometabolic risk factors.</p&gt

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Age at period cessation and trajectories of cardiovascular risk factors across mid and later life

Objective: To examine the association between age at period cessation and trajectories of anthropometry, blood pressure, lipids and glycated haemoglobin (HbA1c) from midlife to age 69 years. / Methods: We used data from the UK Medical Research Council National Survey of Health and Development to examine the association between age at period cessation and trajectories of systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI) and waist circumference (WC) from 36 to 69 years and trajectories of triglyceride, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and HbA1c from 53 to 69 years. / Results: We found no evidence that age at period cessation was associated with trajectories of log triglyceride, LDL-C and HDL-C from 53 to 69 years and trajectories of SBP or DBP from 36 to 69 years, regardless of whether period cessation occurred naturally or due to hysterectomy. While we found some evidence of associations of age at period cessation with log BMI, log WC and log HbA1c, patterns were not consistent and differences were small at age 69 years, with confidence intervals that spanned the null value. / Conclusion: How and when women experience period cessation is unlikely to adversely affect conventional cardiovascular risk factors across mid and later life. Women and clinicians concerned about the impact of type and timing of period cessation on conventional cardiovascular intermediates from midlife should be reassured that the impact over the long term is small