Area-level and family-level socioeconomic position and body composition trajectories: longitudinal analysis of the UK Millennium Cohort Study

Background: Inequalities in the trajectories of body composition in childhood and adolescence have been infrequently studied. Despite the importance of environmental factors in obesity development, little research has looked at area-level socioeconomic position, independent of family socioeconomic position. We aimed to assess how inequalities in body composition develop with age. Methods: The Millennium Cohort Study is a longitudinal study of 19 243 families who had a child born between 2000 and 2002 in the UK. Multilevel growth curve models were applied to examine change in fat mass index (FMI), fat free mass index (FFMI; using the Benn index), and fat mass to fat free mass ratio (FM:FFM), measured using Bioelectrical Impedance Analysis, from ages 7 years to 17 years by the Index of Multiple Deprivation (IMD) and household income at baseline. Findings: Inequalities in FMI and FM:FFM ratio are evident at age 7 years and widen with age. At age 17 years, adolescents in the most disadvantaged IMD group had FMI 0·57 kg/mB (B=Benn parameter; 95% CI 0·43 to 0·70) higher and FM:FFM ratio 0·037 (95% CI 0·026 to 0·047) higher compared with the most advantaged group. Disadvantaged socioeconomic position is associated with higher FFMI but is reversed in adolescence after adjustment for FMI. Inequalities were greater in girls at age 7 years (mean FMI 0·22 kg/mB; 95% CI 0·13 to 0·32) compared with boys of the same age (0·05 kg/mB; –0·04 to 0·15, p=0·3), but widen fastest in boys, especially for FMI, in which there was over an 11 times increase in the inequality from age 7 years of 0·05kg/mB (95% CI –0·04 to 0·15) to 0·62 kg/mB at 17 years (0·42 to 0·82). Inequalities for the IMD were similar to income, and persisted at age 17 years independent of family socioeconomic position. Interpretation: Childhood and adolescence is an important period to address inequalities in body composition, as they emerge and widen. Policies should consider FFM as well as FM, and inequalities in the environment. Funding: Medical Research Council, Economic and Social Research Council

Trends in the ability of socioeconomic position to predict individual body mass index: an analysis of repeated cross-sectional data, 1991–2019

Background: The widening of group-level socioeconomic differences in body mass index (BMI) has received considerable research attention. However, the predictive power of socioeconomic position (SEP) indicators at the individual level remains uncertain, as does the potential temporal variation in their predictive value. Examining this is important given the increasing incorporation of SEP indicators into predictive algorithms and calls to reduce social inequality to tackle the obesity epidemic. We thus investigated SEP differences in BMI over three decades of the obesity epidemic in England, comparing population-wide (SEP group differences in mean BMI) and individual-level (out-of-sample prediction of individuals’ BMI) approaches to understanding social inequalities. Methods: We used repeated cross-sectional data from the Health Survey for England, 1991–2019. BMI (kg/m2) was measured objectively, and SEP was measured via educational attainment, occupational class, and neighbourhood index of deprivation. We ran random forest models for each survey year and measure of SEP adjusting for age and sex. Results: The mean and variance of BMI increased within each SEP group over the study period. Mean differences in BMI by SEP group also increased: differences between lowest and highest education groups were 1.0 kg/m2 (0.4, 1.6) in 1991 and 1.3 kg/m2 (0.7, 1.8) in 2019. At the individual level, the predictive capacity of SEP was low, though increased in later years: including education in models improved predictive accuracy (mean absolute error) by 0.14% (− 0.9, 1.08) in 1991 and 1.05% (0.18, 1.82) in 2019. Similar patterns were obtained for occupational class and neighbourhood deprivation and when analysing obesity as an outcome. Conclusions: SEP has become increasingly important at the population (group difference) and individual (prediction) levels. However, predictive ability remains low, suggesting limited utility of including SEP in prediction algorithms. Assuming links are causal, abolishing SEP differences in BMI could have a large effect on population health but would neither reverse the obesity epidemic nor reduce much of the variation in BMI

Clinical aspects of tacrolimus use in paediatric renal transplant recipients

The calcineurin inhibitor tacrolimus, cornerstone of most immunosuppressive regimens, is a drug with a narrow therapeutic window: underexposure can lead to allograft rejection and overexposure can result in an increased incidence of infections, toxicity and malignancies. Tacrolimus is metabolised in the liver and intestine by the cytochrome P450 3A (CYP3A) isoforms CYP3A4 and CYP3A5. This review focusses on the clinical aspects of tacrolimus pharmacodynamics, such as efficacy and toxicity. Factors affecting tacrolimus pharmacokinetics, including pharmacogenetics and the rationale for routine CYP3A5*1/*3 genotyping in prospective paediatric renal transplant recipients, are also reviewed. Therapeutic drug monitoring, including pre-dose concentrations and pharmacokinetic profiles with the available reference values, are discussed. Factors contributing to high intra-patient variability in tacrolimus exposure and its impact on clinical outcome are also reviewed. Lastly, suggestions for future research and clinical perspectives are discussed