Intrauterine Growth Restriction and Developmental Programming of the Metabolic Syndrome: A Critical Appraisal

Abstract

According to the "small baby syndrome hypothesis," low birthweight and intrauterine growth restriction (IUGR) occurring in westernized countries mainly through altered placental flow, have been linked to increased metabolic syndrome risk in later life. Independency and causal mechanisms of this phenomenological association are a matter of controversy. By means of epidemiological as well as experimental methods, using meta-analyses and different rodent models of pre- and/or neonatal malnutrition and altered placental flow (uterine artery ligation; Lig), we systematically addressed the phenomenon. Our data and systematic literature analysis revealed that neither epidemiological nor experimental evidence seems to exist linking prenatal underfeeding, low birthweight, IUGR, or decreased placental flow in rats (Lig-model) as independent risk factors to increased metabolic syndrome risk in later life. Rather, pre- and/or neonatal overfeeding, elevated birthweight, rapid neonatal weight gain, and especially increased adiposity during critical periods of perinatal life may increase long-term risks. Perinatally acquired microstructural and epigenomic alterations in regulatory systems of metabolism and body weight seem to be critical, leading to a cardiometabolic risk disposition throughout life. While experimental data in Lig-offspring seem to be considerably biased, prenatal stress and postnatal overfeeding/rapid neonatal weight gain might be causally linked to a long-term deleterious outcome in growth restricted newborns. From a clinical point of view, prevention of causes of IUGR, as well as avoidance of perinatal overnourishment, might be prophylactic approaches to avoid perinatal programming of cardiometabolic risks.

Detection of expressional changes induced by intrauterine growth restriction in the developing rat pancreas

“…IUGR is associated with an increased incidence of perinatal mortality, 2 as well as an elevated risk of developing metabolic syndrome (MS) later in life, exemplified by coronary heart disease, hypertension, hyperlipidemia, and type 2 diabetes. 3 Several studies have demonstrated that MS occurred in adulthood had close relationship with early growth. 4 Recent, epidemiological data strongly indicate that infants experiencing IUGR due to poor maternal nutrition during pregnancy have a propensity for obesity and MS during adulthood.…”

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

“…Insulin resistance is considered to be a fundamental contributor to metabolic syndrome (1)(2)(3). The underlying causes of IUGR are complicated.…”

Evaluation of kidney dysfunction and angiotensinogen as an early novel biomarker of intrauterine growth restricted offspring rats

“…Most cases of IUGR reportedly result from decreased placenta blood flow (6). A decrease in placenta blood flow by maternal bilateral uterine artery ligation was shown in an animal model; however, relatively few studies have been conducted to evaluate subsequent kidney dysfunction.…”