TABLE 1.

Overview of intrauterine epigenetic factors relevant to subsequent adiposity.

Prenatal variable	Effect
Maternal pre-partum weight and weight gain during pregnancy	In studies comparing siblings born to the same mothers before and after bariatric surgery, the infants developing in the weight reduced, post-bariatric surgery environment show lower adiposity, blood pressure, circulating concentrations of insulin, gene expression relevant to diabetes, autoimmune disease, and vascular disease risk (Guenard et al., 2013). Weight gain during pregnancy has a strong positive correlation with birthweight and the incidence of subsequent childhood obesity (Oken et al., 2009). These correlations are augmented 2–5 fold in mothers with pre-partum obesity compared to those who were neither overweight nor obese prior to pregnancy
Intrauterine nutritional and chemical environment	Maternal diet (overall nutrition, low folate, and low amounts of other methyl donors), diabetes mellitus, use of steroids, antipsychotics or antibiotics, smoking, exposure to chemicals such as bisphenol all alter DNA methylation of genes that favor increased subsequent adiposity (Inadera, 2013)
Prenatal undernutrition	Maternal undernutrition or compromised fuel delivery to the fetus [e.g., placental dysfunction) are all associated with increased risk of intrauterine growth retardation (small for gestational age, SGA)] and with subsequent obesity and acquisition of co-morbidities at lower levels of body fatness (Barker, 1997; Ravelli et al., 1998; Yarbrough et al., 1998; Hattersley and Tooke, 1999; Moore et al., 1999; Godfrey and Barker, 2000) depending upon the timing of intrauterine undernutrition (Ravelli et al., 1976). It has been hypothesized that early intrauterine malnutrition might affect development of hypothalamic feeding circuits while the anti-obesity effects of perinatal malnutrition might be due to suppression of adipocyte formation
Prenatal overnutrition	Prenatal overnutrition is exemplified by the infant of the mother with diabetes (usually gestational) with high ambient glucose. It is difficult to separate the metabolic effects of gestational diabetes and those of maternal adiposity in this population. Gestational diabetes is associated with an increased risk of obesity in the offspring, independent of the degree of maternal obesity (Pettitt et al., 1983, 1987, 1988).
Maternal stress during pregnancy	Metabolic (e.g., obesity, diabetes, undernutrition, and illness), psychiatric (e.g., depression, anxiety, and bereavement), or pharmacological (e.g., steroids, antidepressants, and antibiotics) maternal stressors have all been associated with increased risk of offspring obesity via effects on developing neural systems regulating energy homeostasis, endocrine systems affecting risk of diabetes–including increased activity of the hypothalamic-pituitary-adrenal (HPA) axis, immune system alterations resulting in increased circulating concentrations of pro-inflammatory cytokines, decreased concentrations of adiponectin relative to fat mass, and increased risk of hypertension (Entringer et al., 2012; Entringer and Wadhwa, 2013)