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

Abstract

Background & AimsAdiposity 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.MethodsIndividual 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.ResultsBirth 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.ConclusionsGreater 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.

FTO-dependent function of N6-methyladenosine is involved in the hepatoprotective effects of betaine on adolescent mice

“…Nonalcoholic fatty liver disease (NAFLD) has been rapidly emerging among children and adolescents and is now the most common cause of chronic liver disease in the developed world [2,15,26]. Adolescents with NAFLD also tend to be more insulin resistant and dyslipidemic, but the extent to which these associations are independent of total body fatness is not clearly understood [1,5,27].…”

Associations between early body mass index trajectories and later metabolic risk factors in European children: the IDEFICS study

“…The common denominator of several hypotheses relating early life exposures to later health seems to be faster growth during infancy and childhood [4]. To date, various associations between childhood trajectories of growth, including height, weight or body mass index (BMI), and later outcomes such as non-alcoholic fatty liver disease [6], asthma [7], hypertension [8][9][10], coronary heart disease [11,12] and other cardiovascular (metabolic) risk factors [13][14][15] have been reported. With regard to BMI development during childhood, also the magnitude and timing of the infancy peak and adiposity rebound were suggested to be related to later obesity and metabolic factors [16][17][18].…”

A Life Course Perspective on Health Trajectories and Transitions

“…In ALSPAC and Probit, two large studies with lots of repeated measurements of growth, we have used multilevel models to define growth trajectories across childhood (Howe et al 2013c;Tilling et al 2011b); an approach which is appropriate for repeated measures data and which can incorporate missing data under a missing at random assumption. In these analyses, we have not found strong support for infancy as a sensitive period in relation to a wide range of cardiometabolic risk factors, including blood pressure (central and peripheral), glucose, lipids, insulin, and non-alcoholic fatty liver disease Tilling et al 2011a;Anderson et al 2014).…”