Cord blood adipokines and lipids and adolescent nonalcoholic fatty liver disease

Abstract

Context: Maternal adiposity in pregnancy is associated with offspring adiposity and metabolic dysfunction postnatally, including greater risk of nonalcoholic fatty liver disease (NAFLD). Recent genetic analyses suggest a causal effect of greater maternal body mass index on offspring birth weightandponderal index, but the relative roles of the environment in utero or later in life remains unclear. Objective: We sought to determine whether markers of infant adiposity (birth weight, umbilical cord blood leptin, adiponectin, and lipids) were associated with markers of NAFLD in adolescence. Design, Setting, and Participants: This was aUK prospective birth cohort with 17 years of follow-up with liver function tests (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase) (n = 1037 participants), and ultrasound scan assessed liver fat, volume, and sheer velocity at age 17 (n = 541 participants). Missing covariate data were imputed. Main Outcomes: Ultrasound and biochemical measures of NAFLD were measured. Results: Birth weight, cord blood leptin, and adiponectin were not associated with a diagnosis of NAFLD. In adjusted analyses, 2 of 42 associations attained conventional 5% levels of significance. Birth weight was positively associated with liver volume (1.0% greater per 100 g [95% confidence interval 0.5%-2.0%]). Cord high-density lipoprotein-cholesterol was positively associated with alanine aminotransferase (11.6% higher per 1 mmol/L [95% confidence interval 0.3, 23.4]); however, this association was primarily mediated via offspring adiposity. Conclusions: In this extensive analysis, we found little evidence measurements of infant fat mass and birth size were related to adolescent markers of NAFLD. The association between birth weight and adolescent liver volume may indicate the contribution of greater organ size to birth weight and tracking of organ size.