Modeling fetal adaptation to nutrient restriction: testing the fetal origins hypothesis with a supply-demand model.

The fetal origins hypothesis (FOH) posits that fetal adaptations to nutritional insufficiency elevate future risk for cardiovascular disease (CVD). Although birth weight (BW) remains the most commonly used index of fetal nutritional sufficiency in FOH research, it is a poor index of fetal nutrition because it is also influenced by genes, epigenetic effects and other nonnutritional factors. This paper uses data from the Cebu Longitudinal Health and Nutrition Survey (CLHNS) to explore an alternate strategy--the supply-demand model--as a means to model fetal nutritional sufficiency, adaptation and cardiovascular programming. Specifically, it is hypothesized that small size should be associated with elevated CVD risk, but only when there is corroborating evidence that the individual had a higher growth potential, was born to a nutritionally stressed mother, or both. Using low density lipoprotein cholesterol (LDL-C) and systolic blood pressure (SBP) as markers of CVD risk, the predictions of the model are only met for LDL-C and only in males. There is evidence for an association between maternal nutritional status and male offspring SBP, but this relationship is independent of fetal nutritional sufficiency as defined by the model. Thus, although both the LDL-C and SBP findings support the general hypothesis that the prenatal milieu has long-term implications for CVD risk in males, only the patterns observed for LDL-C are consistent with the prediction that fetal nutritional sufficiency is key to CVD programming.