ABSTRACT
Childhood obesity continues to be a significant public health burden, with almost one-third of children in the United States classified as overweight or obese (≥85th percentile of weight for height).[1] The original “Barker hypothesis”[2] (also known as the fetal origins of adult disease hypothesis) postulated, based on epidemiological evidence available in the early 1990s, that fetal life was a critical period for the development of later, adult chronic diseases. Later on, empirical evidence began to accumulate identifying developmental pathways and mechanisms that increase the likelihood of excess adiposity and increased risk of type 2 diabetes (T2D) among offspring. Epidemiologic studies have demonstrated that both lowand high-birth weight offspring have increased obesity in later life, though this is likely through different mechanisms. Thus, intrauterine exposures resulting in both restricted and exacerbated fetal growth also lead to in-
creased adiposity later in the life course.[3, 4] Fetal growth restriction occurs as a result of inadequate fuel substrates and oxygenation, resulting in a phenotypically undernourished infant. Excessive fetal growth occurs when the fetus is overnourished by excess maternal fuels, which can deregulate the fetus' adipoinsular axis, resulting in altered energy and appetite regulation, and disordered adipocyte metabolism.[5] The adipoinsular axis, which involves the hormones insulin and leptin, may play a significant role in the development of adiposity and diabetes. The pathway related to excess maternal fuels results in increased fetal and neonatal fat mass and subsequent childhood obesity, which increases the likelihood of cardiovascular disease (CVD), T2D, metabolic syndrome, and other morbidities later in life. Studies have shown that developmental overnutrition can occur as a result of the fetus being exposed to an excess of maternal fuels from maternal diabetes,[6-8] maternal prepregnancy overweight and obesity,[9, 10] and excess gestational weight gain (GWG).[11-13] Based on this and other evidence reviewed herein, it appears that a transgenerational vicious cycle is set in motion, which perpetuates and likely contributes to the rise in the prevalence and risk for early-onset obesity and T2D.[14, 15]
The present review examines the evidence that an altered intrauterine environment results in long-term consequences for the offspring. It also explores the history and concept of developmental overnutrition along with the evidence of the effect it has on childhood adiposity and T2D, public health consequences, potential preventive approaches, and future directions for research.
