Over the past 20 years the scientific literature has reported important relationships between placental size and augmented risk of cardiovascular disease in the offspring. Of 382 men and women who died from cardiovascular disease, the placental ratios were positively associated with cardiovascular disease mortality. The presence of advanced villous maturation (AVM) is a sensitive feature of relative uteroplacental insufficiency (UPI). Prepregnancy nutritional status may be more important to placental and fetal growth than maternal diet and weight gain during pregnancy. Sufficient macro- and micronutrient provisions during gestation are critical for proper fetal growth and development. The maternal environment and placental uptake and metabolism of nutrients probably affect epigenetic mechanisms within the placenta. There is increasing evidence that flow patterns reflect altered haemodynamic forces that impart signals to heart structures that regulate chamber growth and valve formation. Several important models of placental insufficiency have been developed in sheep.