Intrauterine nutrition: its importance during critical periods for cardiovascular and endocrine development

Abstract

Experimental investigations in animals have highlighted the role of early reduced calorie and protein nutrition on fetal cardiovascular development, and the occurrence of a transition from a low fetal arterial blood pressure in late gestation to a high arterial blood pressure postnatally. These observations may explain the correlation between health, including appropriate nutrition, in pregnant women and the outcome of their pregnancies. Emphasis has been placed on low birth weight infants who have an increased risk of developing cardiovascular diseases, including hypertension, coronary heart disease and stroke in adulthood. Vascular pathology in adults is not always associated with low birth weight and animal experiments indicate that substantial changes in cardiovascular and endocrine function can result from maternal or fetal undernutrition without impairing fetal growth. Experimental investigation on organogenesis shows the pivotal role of adequate protein availability as well as total caloric intake. Amino acid metabolism in the feto-maternal unit appears to have a key influence on the development of organs involved in chronic degenerative disease in the adult. Experimental investigation has also highlighted the role of carbohydrate metabolism and its effect on the fetus in this respect. Either restriction of protein intake or diabetes in pregnant rats has intergenerational effects at least on the endocrine pancreas and the brain. Further investigation is needed to clarify the mechanisms involved and lead to a new understanding of the importance of nutrition during pregnancy. This will provide an important approach to the primary prevention of diabetes and chronic degenerative diseases.

Figure 1. Basal mean arterial pressure (A) and ACTH response to administration of CRH + AVP (B) in control (□) and nutrient restricted (▪) fetuses (113-127 days gestation) and lambs (84 ± 4.4 days)

Values are means ±s.e.m. Arterial pressure is shown as the mean of measurements made over a 2 week period in the fetus, and as the mean of measurements made on a single day in the lamb. ACTH responses to CRH + AVP challenge were measured for 180 min after drug administration in the fetus, and for 60 min in the lamb; ACTH data are shown as the cumulative response over the first 15 min following drug administration, with samples taken every 5 min. Blood pressure data were compared by Student's unpaired t test, and ACTH data by two-way analysis of variance followed by Dunnett's post-hoc test (*P < 0.05). Fetal basal blood pressure, and ACTH responses to CRH + AVP were significantly reduced following maternal nutrient restriction. Postnatally, basal blood pressure and ACTH responses were significantly greater in lambs of undernourished mothers. Adapted from Hawkins et al. (1997, 1998).

Figure 2. Effects of a 30% restriction in global diet during pregnancy on the mean arterial pressure (A) and responses of small resistance arteries to the thromboxane A₂ mimetic U46619 in vitro (B) of male offspring

Offspring of nutritionally restriced dams (NR) show higher arterial blood pressure at both 100 and 200 days postnatally, compared with controls (C). In addition, small artery contractile responses, measured as maximal tension (E_max) to U46619 as a percentage of maximal K⁺-induced tension, are greater in NR than in C at both ages. All data are means ±s.e.m.*P < 0.05 NR vs. C by the Mann-Whitney U test. Data from Ozaki et al. (1998).

Figure 3. Weight (means ±s.d.) of the fetus (A) and placenta (B) in late gestation in spontaneously hypertensive rats (SHR; ▪) and normotensive Wistar-Kyoto controls (WKY; □)

The lower fetal weight in mid-gestation in SHR is not seen in late gestation, and this effect is associated with greater placental weight. Note that gestation is slightly longer in SHR than WKY. * P less than 0.01 by unpaired t test; ** P less than 0.01 by ANOVA, SHR vs. WKY. Adapted from Lewis et al. (1997).