During the Dutch Famine of 1944-1945, relief food rations provided <900 kcal/day. We will examine if this stressed fetal environment has a significant effect on adult survival by linking military examination records for men born from 1944-1947 to mortality records. We will ascertain vital status and cause of death through 2010, when the age of the surviving men will be 63-67 years. We have established collaborative agreements with the Dutch Ministry of Defense and other key agencies for sampling, tracing of deaths, and establishing cause of death. Our study addresses two research questions: (1) what is the effect of prenatal famine exposure on mortality through age 63-67 years? We will identify the 25,000 men born November 1944 - March 1946 in the six cities most affected by the famine. Men will be categorized based on date of birth as having famine exposure at different stages of gestation. As controls with no prenatal famine exposure we will select a random sample of 10,000 men born in the same cities, but born before or conceived after the famine. (2) How do new statistical methodologies further refine existing approaches to assessing the long-term effects of prenatal famine exposures? We will use Functional Data Analysis to incorporate information on average weekly caloric rations over the entire gestation period to model the effects of variation in food rations on selected characteristics at age 18 and on subsequent all-cause and cause-specific mortality. This is a unique opportunity to quantify the role of the prenatal environment on mortality through age 63-67 years in a national birth cohort, with complete ascertainment of date and cause of death provided by national registries. The famine birth cohorts have now reached the age where mortality rates are increasing rapidly, providing excellent study power to detect even modest effects (hazard ratios ~1.2) of prenatal famine on survival. The circumstances of the famine provide a quasi-experimental model to study profound changes in the human fetal environment during specific periods of gestation. The Dutch famine has already informed public health about long-term effects of changes in the prenatal environment in humans and has enormous potential for doing so in the future ? ? We will look at the effects of prenatal famine exposure on mortality through age 63-67 years. We will use study records from 25,000 men born between November 1944 - March 1946 in the six cities most affected by a severe war-time famine in the Netherlands. Men will be classified by date and place of birth as having famine exposure at different stages of gestation. 10,000 study controls will be selected from men with no prenatal famine exposure, and dates and cause of death will be compared for men exposed in different trimesters of pregnancy. The study findings will be relevant in many setting across the world. ? ? ? ?
