Early origins of longevity: prenatal exposures to food shortage among early Utah pioneers.

Undernutrition during critical or sensitive prenatal periods may 'program' the fetus for increased chronic disease and mortality in later life. Using birth cohorts that were or were not exposed to severe food shortage in Utah in the mid-19th century, this study examines how in utero exposure to undernutrition is associated with mortality after age 50. The Utah Population Database is used to identify 1392 prenatally exposed individuals and 29,022 individuals from subsequent, unexposed birth cohorts. Gompertz hazards with parametric frailty show that males born between April and June of the famine period (and hence exposed during critical periods in utero during the winter months) have higher mortality risks compared with post-famine cohorts. Alternative Cox non-proportional hazard models suggest that females born during the same period have higher initial mortality risks (starting at age 50) that decline over time creating a mortality crossover with unexposed women at approximately age 70, a result not found for men. An ancillary sibling analysis that uses shared frailty survival models to compare individuals with prenatal exposure to undernutrition to their younger (post-famine) same-sex siblings finds no significant differences in adult mortality for males but the pattern for females support the findings from the previous analysis. Although findings are sensitive to model choice, this study presents evidence that is consistent with an association between undernutrition in utero and adult mortality, shows that effects may be sensitive to the duration and gestational period of exposure, and illustrates the differential exposure effects between genders.