Consequences of intra-uterine growth retardation for postnatal growth, metabolism and pathophysiology

摘要

Intra-uterine growth retardation (IUGR), caused by maternal undernu-trition or placental insufficiency, is usually associated with disproportionately large reductions in the growth of some feta! organs and tissues fthymus, liver, spleen, thyroid) andimpaired cellular development of other tissues (small intestine, secondary wool follicles, skeletal muscle). Growth of other tissues, most notably brain, is relatively unimpaired. In our recent study of postnatal consequences of IUGR in the offspring ofprolific ewes, growth-retarded newborn lambs tended to be hypoglycaemic and showed sluggish postnatal engagement of the growth hormone (GH)-insulin-like growth factor (IGF) system. When artificially reared in an optimum environment, low birth weight lambs grew at rates similar to those of normal lambs. However, low birth weight lambs were fatter at any given weight, apparently related to their high energy intakes, especially soon after birth, had low maintenance energy requirements, and limited capacityfor bone and muscle growth. These growth characteristics were accompanied by higher plasma concentrations of GH and leptin, and lower concentrations of insulin-like growth factor I (IGF-I) during the first 2 weeks of postnatal life, and higher concentrations of insulin during subsequent growth up to 20 kg body weight. Emerging evidence indicates that in sheep, as in rodents, fetal programming of postnatal cardiovascular and metabolic dysfunctions is associated with IUGR and may be mediated partly by overexposure of the fetus to cortisol. Similar postnatal responses can be elicited by maternal undernutrition or cortisol treatment in early to mid-pregnancy without changing the growth of the fetus or placenta.