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This chapter uses new epidemiological data to examine the role of materno-placental interactions in initiating chronic disease in the offspring. The size, weight and shape of the placenta are all subject to wide variations. Its size reflects its ability to transfer nutrients. In humans, placental growth responds to maternal influences. Maternal anemia and high maternal body mass index are associated with a high placental weight to birth weight ratio. The observations on hypertension established that the relation between placental size/shape and fetal programming depend on the mother. There are similar materno-placental interactions in the programming of coronary heart disease. Growth of the placental surface is polarized from the time of implantation. The human fetus may attempt to compensate for undernutrition by expansion of the placental surface along its minor axis. The maternal/ placental programming of chronic disease differs in boys and girls.