Prenatal Under Nutrition and Mortality Through Age 63 Project

描述（由申请人提供）：在1944-1945年荷兰饥荒期间，救济口粮提供<900千卡/天。我们将通过将1944-1947年出生的男性的军事检查记录与死亡率记录联系起来，研究这种压力胎儿环境是否对成年存活率有显著影响。我们将在2010年之前查明重要状况和死亡原因，届时幸存男子的年龄将达到63-67岁。我们与荷兰国防部和其他主要机构就抽样、追踪死亡和确定死亡原因达成了合作协议。我们的研究解决了两个研究问题：(1)产前饥荒暴露对63-67岁死亡率的影响是什么？我们将找出1944年11月至1946年3月在六个受饥荒影响最严重的城市出生的25000人。男性将根据出生日期被分类为在怀孕的不同阶段有饥荒暴露。作为没有产前饥荒暴露的对照，我们将随机选择在同一城市出生的10,000名男性，但在饥荒之前出生或之后怀孕。(2)新的统计方法如何进一步完善评估产前饥荒暴露长期影响的现有方法？我们将使用功能数据分析来整合整个妊娠期平均每周热量配给的信息，以模拟食物配给变化对18岁时选定特征以及随后的全因和特定原因死亡率的影响。这是一个独特的机会，可以在国家出生队列中量化产前环境对63-67岁之间死亡率的作用，并完全确定国家登记处提供的死亡日期和原因。饥荒出生队列现已达到死亡率迅速上升的年龄，这为检测产前饥荒对生存的影响（风险比约1.2）提供了极好的研究能力。饥荒的情况提供了一个准实验模型来研究人类胎儿环境在妊娠特定时期的深刻变化。荷兰的饥荒已经使公共卫生部门了解了人类产前环境变化的长期影响，并且在未来有巨大的潜力这样做

DESCRIPTION (provided by applicant): 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.