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Many epidemiological studies in diverse populations have demonstrated a link between low birth weight and subsequent disease. This evidence has given rise to the fetal origins hypothesis, which suggests that exposure of the fetus to an adverse environment in utero leads to permanent programming of tIssue function and a risk of cardiovascular disease. An alternative hypothesis is that low birth weight and adult cardiovascular disease are independent features of a genetic predisposition to cardiovascular disease. This review describes evidence that the programming phenomenon may not be limited to the first generation offspring. Results of human and animal studies identify intergenerational programmed effects on both birth weight and cardiovascular disease. This may represent a mechanism for the non-genetic inheritance of a predisposition to low birth weight and adverse cardiovascular risk across a number of generations.

The intergenerational effects of fetal programming: non-genomic mechanisms for the inheritance of low birth weight and cardiovascular risk