Intrauterine Growth Restriction: Hungry for an Answer

Abstract

Intrauterine growth restriction (IUGR) has been defined in several ways, but in general describes a condition in which the fetus exhibits poor growth in utero. This complication of pregnancy poses a significant public health burden as well as increased morbidity and mortality for the offspring. In human IUGR, alteration in fetal glucose and insulin homeostasis occurs in an effort to conserve energy and survive at the expense of fetal growth in an environment of inadequate nutrient provision. Several animal models of IUGR have been utilized to study the effects of IUGR on fetal glucose handling, as well as the postnatal reprogramming of energy metabolite handling, which may be unmasked in adulthood as a maladaptive propensity for cardiometabolic disease. This developmental programming may be mediated in part by epigenetic modification of essential regulators of glucose homeostasis. Several pharmacological therapies and nonpharmacological lifestyle modifications have shown early promise in mitigating the risk for or severity of adult metabolic phenotypes but still require further study of unanticipated and/or untoward side effects.

FIGURE 1.

The postnatal and adult effects of intrauterine growth restriction Figure was modified from Ref. 116a with permission from Nature Reviews Endocrinology.

FIGURE 2.

Summary of overall and organ-specific glucose and insulin metabolism adaptations in IUGR, the fetus, and the adult Red coloring indicates finding in animal models of IUGR, and blue indicates findings in human IUGR studies. Discrepancies exist between human and animal studies, and among animal studies depending on experimental conditions.

FIGURE 3.

Therapeutic interventions for the adult risk of cardiometabolic disease seen in IUGR