Emma L Anderson

The Prevalence of Non-Alcoholic Fatty Liver Disease in Children and Adolescents: A Systematic Review and Meta-Analysis

Background & Aims Narrative reviews of paediatric NAFLD quote prevalences in the general population that range from 9% to 37%; however, no systematic review of the prevalence of NAFLD in children/adolescents has been conducted. We aimed to estimate prevalence of non-alcoholic fatty liver disease (NAFLD) in young people and to determine whether this varies by BMI category, gender, age, diagnostic method, geographical region and study sample size. Methods We conducted a systematic review and meta-analysis of all studies reporting a prevalence of NAFLD based on any diagnostic method in participants 1–19 years old, regardless of whether assessing NAFLD prevalence was the main aim of the study. Results The pooled mean prevalence of NAFLD in children from general population studies was 7.6% (95%CI: 5.5% to 10.3%) and 34.2% (95% CI: 27.8% to 41.2%) in studies based on child obesity clinics. In both populations there was marked heterogeneity between studies (I2 = 98%). There was evidence that prevalence was generally higher in males compared with females and increased incrementally with greater BMI. There was evidence for differences between regions in clinical population studies, with estimated prevalence being highest in Asia. There was no evidence that prevalence changed over time. Prevalence estimates in studies of children/adolescents attending obesity clinics and in obese children/adolescents from the general population were substantially lower when elevated alanine aminotransferase (ALT) was used to assess NAFLD compared with biopsies, ultrasound scan (USS) or magnetic resonance imaging (MRI). Conclusions Our review suggests the prevalence of NAFLD in young people is high, particularly in those who are obese and in males.

The Prevalence of Non-Alcoholic Fatty Liver Disease in Children and Adolescents

Background & Aims Narrative reviews of paediatric NAFLD quote prevalences in the general population that range from 9% to 37%; however, no systematic review of the prevalence of NAFLD in children/adolescents has been conducted. We aimed to estimate prevalence of non-alcoholic fatty liver disease (NAFLD) in young people and to determine whether this varies by BMI category, gender, age, diagnostic method, geographical region and study sample size. Methods We conducted a systematic review and meta-analysis of all studies reporting a prevalence of NAFLD based on any diagnostic method in participants 1–19 years old, regardless of whether assessing NAFLD prevalence was the main aim of the study. Results The pooled mean prevalence of NAFLD in children from general population studies was 7.6% (95%CI: 5.5% to 10.3%) and 34.2% (95% CI: 27.8% to 41.2%) in studies based on child obesity clinics. In both populations there was marked heterogeneity between studies (I2 = 98%). There was evidence that prevalence was generally higher in males compared with females and increased incrementally with greater BMI. There was evidence for differences between regions in clinical population studies, with estimated prevalence being highest in Asia. There was no evidence that prevalence changed over time. Prevalence estimates in studies of children/adolescents attending obesity clinics and in obese children/adolescents from the general population were substantially lower when elevated alanine aminotransferase (ALT) was used to assess NAFLD compared with biopsies, ultrasound scan (USS) or magnetic resonance imaging (MRI). Conclusions Our review suggests the prevalence of NAFLD in young people is high, particularly in those who are obese and in males.

Facilitating professional liaison in collaborative care for depression in UK primary care; a qualitative study utilising normalisation process theory

BackgroundCollaborative care (CC) is an organisational framework which facilitates the delivery of a mental health intervention to patients by case managers in collaboration with more senior health professionals (supervisors and GPs), and is effective for the management of depression in primary care. However, there remains limited evidence on how to successfully implement this collaborative approach in UK primary care. This study aimed to explore to what extent CC impacts on professional working relationships, and if CC for depression could be implemented as routine in the primary care setting.MethodsThis qualitative study explored perspectives of the 6 case managers (CMs), 5 supervisors (trial research team members) and 15 general practitioners (GPs) from practices participating in a randomised controlled trial of CC for depression. Interviews were transcribed verbatim and data was analysed using a two-step approach using an initial thematic analysis, and a secondary analysis using the Normalisation Process Theory concepts of coherence, cognitive participation, collective action and reflexive monitoring with respect to the implementation of CC in primary care.ResultsSupervisors and CMs demonstrated coherence in their understanding of CC, and consequently reported good levels of cognitive participation and collective action regarding delivering and supervising the intervention. GPs interviewed showed limited understanding of the CC framework, and reported limited collaboration with CMs: barriers to collaboration were identified. All participants identified the potential or experienced benefits of a collaborative approach to depression management and were able to discuss ways in which collaboration can be facilitated.ConclusionPrimary care professionals in this study valued the potential for collaboration, but GPs’ understanding of CC and organisational barriers hindered opportunities for communication. Further work is needed to address these organisational barriers in order to facilitate collaboration around individual patients with depression, including shared IT systems, facilitating opportunities for informal discussion and building in formal collaboration into the CC framework.Trial registrationISRCTN32829227 30/9/2008.

Weight trajectories through infancy and childhood and risk of non-alcoholic fatty liver disease in adolescence: The ALSPAC study

Background & Aims Adiposity is a key risk factor for NAFLD. Few studies have examined prospective associations of infant and childhood adiposity with subsequent NAFLD risk. We examined associations of weight-for-height trajectories from birth to age 10 with liver outcomes in adolescence, and assessed the extent to which associations are mediated through fat mass at the time of outcome assessment. Methods Individual trajectories of weight and height were estimated for participants in the Avon Longitudinal Study of Parents and Children using random-effects linear-spline models. Associations of birthweight (adjusted for birth length) and weight change (adjusted for length/height change) from 0–3 months, 3 months–1 y, 1–3 y, 3–7 y, and 7–10 y with ultrasound scan (USS) determined liver fat and stiffness, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) at mean age 17.8 y were assessed with linear and logistic regressions. Mediation by concurrent fat mass was assessed with adjustment for fat mass at mean age 17.8 y. Results Birth weight was positively associated with liver stiffness and negatively with ALT and AST. Weight change from birth to 1 y was not associated with outcomes. Weight change from 1–3 y, 3–7 y, and 7–10 y was consistently positively associated with USS and blood-based liver outcomes. Adjusting for fat mass at mean age 17.8 y attenuated associations toward the null, suggesting associations are largely mediated by concurrent body fatness. Conclusions Greater rates of weight-for-height change between 1 y and 10 y are consistently associated with adverse liver outcomes in adolescence. These associations are largely mediated through concurrent fatness.

Associations of postnatal growth with asthma and atopy: the PROBIT Study.

It has been hypothesised that postnatal weight and length/height gain are variously related to wheeze, asthma and atopy; however, supporting evidence is limited and inconsistent.

Nonalcoholic Fatty Liver Disease, Liver Fibrosis, and Cardiometabolic Risk Factors in Adolescence: A Cross-Sectional Study of 1874 General Population Adolescents

Context: The impact of adolescent nonalcoholic fatty liver disease (NAFLD) on health, independent of fat mass, is unclear. Objective: The objective of the study was to determine the independent (of total body fat) association of ultrasound scan (USS)-determined NAFLD with liver fibrosis, insulin resistance, and dyslipidemia among healthy adolescents. Design: This was a cross-sectional analysis in participants from a UK birth cohort. Participants: One thousand eight hundred seventy-four (1059 female) individuals of a mean age of 17.9 years participated in the study. Main Outcomes: USS assessed liver stiffness (shear velocity, an indicator of fibrosis) and volume, fasting glucose, insulin, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine amino transferase, aspartate amino transferase, γ-glutamyltransferase, and haptoglobin. Results: The prevalence of NAFLD was 2.5% [95% confidence interval (CI) 1.8–3.3] and was the same in females and males. Dual-energy X-ray absorptiometry determined total body fat mass was strongly associated with USS NAFLD: odds ratio 3.15 (95% CI 2.44–4.07) per 1 SD (∼10 kg) fat mass. Those with NAFLD had larger liver volumes and greater shear velocity. They also had higher fasting glucose, insulin, triglycerides, low-density lipoprotein cholesterol, alanine amino transferase, aspartate amino transferase, γ-glutamyltransferase, and haptoglobin and lower high-density lipoprotein cholesterol. Most associations were independent of total body fat. For example, after adjustment for fat mass and other confounders, hepatic shear velocity [mean difference 22.8% (95% CI 15.6–30.5)], triglyceride levels [23.6% (95% CI 6.0–44.2)], and insulin [39.4% (95% CI 10.7–75.5)] were greater in those with NAFLD compared with those without NAFLD. Conclusion: In healthy European adolescents, 2.5% have USS-defined NAFLD. Even after accounting for total body fat, those with NAFLD have more adverse levels of liver fibrosis and cardiometabolic risk factors.

Associations of postnatal growth with asthma and atopy

It has been hypothesised that postnatal weight and length/height gain are variously related to wheeze, asthma and atopy; however, supporting evidence is limited and inconsistent.

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

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. 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. 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. Conclusion Our results suggest that in healthy adolescent females, AMH is not associated with cardiometabolic risk factors.

Estimating trajectories of energy intake through childhood and adolescence using linear-spline multilevel models

Background: Methods for the assessment of changes in dietary intake across the life course are underdeveloped. Methods: We demonstrate the use of linear-spline multilevel models to summarize energy-intake trajectories through childhood and adolescence and their application as exposures, outcomes, or mediators. The Avon Longitudinal Study of Parents and Children assessed children’s dietary intake several times between ages 3 and 13 years, using both food frequency questionnaires (FFQs) and 3-day food diaries. We estimated energy-intake trajectories for 12,032 children using linear-spline multilevel models. We then assessed the associations of these trajectories with maternal body mass index (BMI), and later offspring BMI, and also their role in mediating the relation between maternal and offspring BMIs. Results: Models estimated average and individual energy intake at 3 years, and linear changes in energy intake from age 3 to 7 years and from age 7 to 13 years. By including the exposure (in this example, maternal BMI) in the multilevel model, we were able to estimate the average energy-intake trajectories across levels of the exposure. When energy-intake trajectories are the exposure for a later outcome (in this case offspring BMI) or a mediator (between maternal and offspring BMI), results were similar, whether using a two-step process (exporting individual-level intercepts and slopes from multilevel models and using these in linear regression/path analysis), or a single-step process (multivariate multilevel models). Trajectories were similar when FFQs and food diaries were assessed either separately, or when combined into one model. Conclusions: Linear-spline multilevel models provide useful summaries of trajectories of dietary intake that can be used as an exposure, outcome, or mediator.

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.