Causes of Intrauterine Growth Restriction and the Postnatal Development of the Metabolic Syndrome

Abstract

The term intrauterine growth restriction (IUGR) is assigned to newborns with a birth weight and/or birth length below the 10th percentile for their gestational age and whose abdominal circumference is below the 2.5th percentile with pathologic restriction of fetal growth. IUGR is usually due to maternal, fetal, or placental factors. However, many IUGR cases have unknown underlying cause. Recent studies focus on new factors that can influence fetal development and birth outcome like the timing and the type of fetal nutrition, maternal psychosocial stress and personality variables, 11beta-hydroxysteroid dehydrogenase type 2 placental activity, the activity of the neuroendocrine system that mediates the effects of psychosocial stress, and the role of proinflammatory cytokines and of oxidative stress. Data have shown that IUGR is associated with a late life increased prevalence of metabolic syndrome, a condition associating obesity with hypertension, type 2 diabetes mellitus (DM2), and cardiovascular disease. Recent data demonstrated that the diabetes-associated mortality appears to be disproportionately concentrated among individuals of abnormal birth weight.

Downregulating SOCS3 with siRNA ameliorates insulin signaling and glucose metabolism in hepatocytes of IUGR rats with catch-up growth

“…The underlying causes of IUGR are complicated. In developed countries, poor placental function and cigarette smoking during pregnancy are the most common factors causing IUGR, although maternal malnutrition is the major determinant of IUGR in developing countries (4). Approximately 85-90% of infants with IUGR demonstrate catch-up growth during the first 2 y, and those who display a catch-up in body weight are more prone to insulin resistance (5).…”

Low Birthweight Increases the Likelihood of Severe Steatosis in Pediatric Non-Alcoholic Fatty Liver Disease

“…Intrauterine growth retardation (IUGR) is associated with the development of clinical manifestations of the MetS and increased cardiovascular risk in adulthood [10] and is a strong risk factor for NAFLD since childhood [17,18]. We had previously shown the association of paediatric NAFLD with IUGR; the prevalence of SGA in children with NAFLD resulted about four times higher compared to the average percentage of the hospitalized children [18].…”

“…Perturbations of intrauterine environment during pregnancy (i.e. placental insufficiency) may deeply affect foetus growth causing intrauterine growth retardation (IUGR) [10,11]. The American College of Obstetricians and Gynecologists has defined small for gestational age (SGA) a newborn with an actual birthweight below the 10 th weight percentile for his/her age in gestational weeks [12].…”

Maternal Undernutrition and Long-Term Effects on Hepatic Function

“…Barker explained this phenomenon with the "predictive adaptive response" hypothesis, which suggests that "adverse events during development induce adaptations suited for survival in a similar predictive environment but can become maladaptive if a mismatch to the predictive environment occurs, leading to a thrifty phenotype" [32,33]. Since IUGR leads to major decreases in fetal liver development, it seems conceivable that the liver has the most to gain in growth during postnatal life [19,20]. Animal models of IUGR support that the undernourished liver undergoes rapid postnatal catch-up growth leading to further metabolic dysfunction, but there is evidence from human studies as well [34][35][36].…”

“…The early evidence that an impairment of liver size and/or function was involved came from the fact that there was a strong correlation between reduced abdominal circumference at birth with elevated total and LDL cholesterol in adulthood [18]. Secondly, intrauterine growth restriction (IUGR), caused by either placental insufficiency or maternal malnutrition, often results in asymmetric organ development whereby there is a reduction in the growth of less essential organs such as the liver, lungs, and kidneys [19,20]. Thirdly, there is a strong inverse relationship between birth weight and obesity or glucose intolerance; both under the regulation of the liver [21][22][23][24].…”