Programming of weight and obesity across the lifecourse by the maternal metabolic exposome: A systematic review

Exposome research aims to comprehensively understand the multiple environmental exposures that influence human health. To date, much of exposome science has focused on environmental chemical exposures and does not take a lifecourse approach. The rising prevalence of obesity, and the limited success in its prevention points to the need for a better understanding of the diverse exposures that associate with, or protect against, this condition, and the mechanisms driving its pathogenesis. The objectives of this review were to 1. evaluate the evidence on the maternal metabolic exposome in the programming of offspring growth/obesity and 2. identify and discuss the mechanisms underlying the programming of obesity. A systematic review was conducted following PRISMA guidelines to capture articles that investigated early life metabolic exposures and offspring weight and/or obesity outcomes. Scientific databases were searched using pre-determined indexed search terms, and risk of bias assessments were conducted to determine study quality. A final total of 76 articles were obtained and extracted data from human and animal studies were visualised using GOfER diagrams. Multiple early life exposures, including maternal obesity, diabetes and adverse nutrition, increase the risk of high weight at birth and postnatally, and excess adipose accumulation in human and animal offspring. The main mechanisms through which the metabolic exposome programmes offspring growth and obesity risk include epigenetic modifications, altered placental function, altered composition of the gut microbiome and breast milk, and metabolic inflammation, with downstream effects on development of the central appetite system, adipose tissues and liver. Understanding early life risks and protectors, and the mechanisms through which the exposome modifies health trajectories, is critical for developing and applying early interventions to prevent offspring obesity later in life.