No abstract

Nutrient supply to the fetus is a key factor in the regulation of fetal growth. However, the direct supply of nutrients to provide building blocks for tissue growth is likely to be only a minor component of this regulation. The indirect effects of nutrition on fetal endocrine and metabolic status, and on the interaction between the fetus, placenta and mother all of which must be coordinated to allow fetal growth are also important. Maternal undernutrition may alter the growth of the fetus and its different component tissues in a way which cannot be explained solely on the basis of reduced substrate supply during the rapid growth phase of the tissues involved. Adaptation to altered substrate supply, during both undernutrition and refeeding, involves sequential changes in the metabolic and endocrine interactions between the fetus and the placenta. In addition, undernutrition has long-term consequences for the fetus. There is evidence for nutritional programming of fetal endocrine and cardiovascular systems before birth. Nutritional effects may also persist over more than one generation. The effects of nutrition on fetal growth are far more complex than simply those of substrate deprivation.

We investigated the effect of restoration of normoglycaemia or normoinsulinaemia in fetuses of starved ewes on plasma IGF-I and IGF-II concentrations. Paired maternal and fetal blood samples were taken during an initial 2-day control period, after 48 h of maternal starvation, during 24 h fetal infusion of glucose (n = 6) or insulin (n = 4) while maintaining maternal starvation and after 48 h maternal refeeding. After 48 h starvation maternal and fetal plasma IGF-I, insulin and blood glucose fell (maternal IGF-I 38.9 +/- 3.6 to 16.4 +/- 1.8 nM and fetal IGF-I 13.2 +/- 0.8 to 7.1 +/- 0.7 nM, both P < 0.05). Fetal plasma IGF-II also fell (147.8 +/- 9.1 to 112.2 +/- 3.8 nM, P < 0.05), but maternal plasma IGF-II rose (71.8 +/- 6.3 to 88.8 +/- 9.2 nM, P = 0.10). Fetal glucose replacement raised fetal plasma IGF-I (11.4 +/- 1.2 nM), IGF-II (149.7 +/- 6.5 nM), insulin and blood glucose to near control values (all P < 0.05). Fetal insulin replacement raised fetal plasma IGF-I (9.0 +/- 0.6 nM) and insulin (all P < 0.05) while IGF-II (105.2 +/- 8.4 nM) and blood glucose remained depressed. Neither fetal infusion had any significant effect on maternal plasma IGF-I (13.1 +/- 1.6 nM), IGF-II (77.5 +/- 8.7 nM), insulin or blood glucose. After 48 h maternal refeeding fetal IGF-I (12.4 +/- 0.4 nM), fetal IGF-II (158.4 +/- 8.9 nM), maternal IGF-II (67.1 +/- 3.0 nM), maternal and fetal insulin and glucose had returned to near control values in both groups. Maternal IGF-I remained below control values (24.7 +/- 2.5 nM, P < 0.05). The data suggest that fetal IGF-I and IGF-II are independently regulated in the fetal circulation. While glucose plays an important role in the regulation of both IGF-I and IGF-II, the influence of glucose on fetal IGF-I is likely to be mediated by insulin, whereas for IGF-II the effect of glucose is insulin-independent.

Gluckman PD, Harding JE. Fetal growth retardation: underlying endocrine mechanisms and postnatal consequences. Acta Pzediatr 1997; Suppl422: 69-72. Stockholm. ISSN Considerable advance has been made in our understanding of the regulation of fetal growth and of the pathophysiology of intrautehe growth retardation. The dominant determinant of fetal growth is nutrient delivery to the conceptus, and the insulin-like growth factors (IGFs) appear to play a central role in modulating the fetal growth response to the nutritional environment. It has also become clear that events early in gestation, or prior to conception, can be reflected in altered fetal growth and metabolism later in gestation. Intrauterine growth retadation (IUGR) may be due to identifiable genetic or toxic factors or to disordered nutrient delivery. The latter category of IUGR provides the greatest clinical concern with a high incidence of perinatal morbidity and mortality. More recently, epidemiological evidence supported by limited, but growing, experimental data suggest that the postnatal consequences of disturbed fetal growth may include metabolic disease (diabetes mellitus) and cardiovascular disease. This brief review discusses these advances with reference to data from our laboratory. 0 Cardiovascular disease, diabetes mellitus, insulin-like growth factors, intrauterine growth retardation PD Gluckman,

This review focuses on intrauterine growth retardation (IUGR) occurring spontaneously and without a defined infective, toxic or genetic cause. Such fetal growth retardation is generally thought to be a consequence of inadequate provision of nutritional substrates across the placenta.