The fetal origins hypothesis: placental insufficiency and inheritance versus maternal malnutrition in well-nourished populations

The ‘Fetal origins hypothesis’ states that individuals born small because of malnutrition are predisposed to adult diseases. Fetal malnutrition has two main causes, poor maternal nutrition and placental insufficiency. A distinction between these causes is important because it is likely that maternal nutrition has been sufficient in the majority of populations in which the fetal origins hypothesis has been tested. Thus, placental insufficiency is a more reasonable cause of reduced fetal growth in adequately nourished populations. Placental insufficiency is mainly due to inadequate vascular adaptation at the uteroplacental interface (‘poor placentation’). Among women with placental insufficiency syndromes such as pre-eclampsia and ‘idiopathic’ intrauterine growth retardation, there is an increased prevalence of risk factors for cardiovascular diseases. Maternal cardiovascular risk factors may therefore increase the risk of adult diseases in the offspring both through direct inheritance and by interfering with uteroplacental vascular adaptation. The latter may result in placental insufficiency and fetal growth retardation that by itself could cause adult disease (as the Fetal origins hypothesis states). Alternatively, the association between low birth weight for gestational and adult disease could be an epiphenomenon, leaving inheritance as the main explanation for the fetal origins hypothesis, in adequately nourished populations.