Adiposity in children born small for gestational age

Abstract

Epidemiological studies indicate that children born small for gestational age (SGA) have an increased risk of metabolic and cardiovascular disorders as adults. This suggests that foetal undernutrition leads to permanent metabolic alterations, which predispose to metabolic abnormalities upon exposure to environmental factors such as low physical activity and/or high-energy intake in later life (thrifty phenotype hypothesis). However, this relationship is not restricted to foetal undernutrition or intrauterine growth retardation, but is also found for children born premature, or for high birth weight children. Furthermore, early post-natal nutrition, and more specifically catch-up growth, appear to modulate cardiovascular risk as well. Intrauterine growth retardation can be induced in animal models by energy/protein restriction, or ligation of uterine arteries. In such models, altered glucose homeostasis, including low beta-cell mass, low insulin secretion and insulin resistance is observed after a few weeks of age. In humans, several studies have confirmed that children born SGA have insulin resistance as adolescents and young adults. Alterations of glucose homeostasis and increased lipid oxidation can indeed be observed already in non-diabetic children born SGA at early pubertal stages. These children also have alterations of stature and changes in body composition (increased fat mass), which may contribute to the pathogenesis of insulin resistance. Permanent metabolic changes induced by foetal/early neonatal nutrition (metabolic inprinting) may involve modulation of gene expression through DNA methylation, or alterations of organ structure. It is also possible that events occurring during foetal/neonatal development lead to long-lasting alterations of the hypothalamo-pituitary-adrenal axis or the hypothalamo-pituitary-insulin-like growth factor-1 axis.

Pregnancy: An Underutilized Window of Opportunity to Improve Long-term Maternal and Infant Health—An Appeal for Continuous Family Care and Interdisciplinary Communication

“…The thrifty phenotype hypothesis suggests that early malnutrition induces poor development of pancreatic β-cell mass and programs the metabolic syndrome (157–162). LBW was related to high concentrations of split proinsulin, a sign of beta-cell dysfunction, linked to later high blood pressure (163, 164) and to metabolic abnormalities in combination with low physical activity and/or high-energy intake (165). The British Maternal Nutrition Study correlated prenatal micronutrient deficiency with increased insulin resistance in childhood: the offspring of mothers with combined high folate and low vitamin B12 levels were insulin resistant (166).…”

Thrifty energy metabolism in catch-up growth trajectories to insulin and leptin resistance

“…39 Among explanations of how such non-optimal early growth followed by catch-up growth could lead to these metabolic disorders, Eriksson 40 recently underscored the potential importance of impaired growth of organs and tissues that tracks into adulthood, with poor liver growth predisposing them to hepatic insulin resistance and dyslipidaemia, and poor muscle growth resulting in reduced buffering capacity for glucose disposal, and hence predisposing them towards insulin resistance. Tappy 41 has proposed a model in which the metabolic disorders and impaired growth in these individuals born SGA are secondary to growth hormone resistance. According to this model, the consequential decrease in IGF-1 secretion would lead to low growth rates and impaired glucose metabolism, while the increase in body fat would lead to insulin resistance through increased plasma FFAs.…”

The feto-placental endothelium in pregnancy pathologies

“…Recent data clearly demonstrate that the intrauterine environment has a persistent impact on the development of the offspring [4,43]. GDM is associated with an increased risk to develop Type-2 diabetes, obesity or cardiovascular disease in later life.…”