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，研究这种应激的胎儿环境是否对成年人的生存有显著影响。到2010年，我们将确定生命状况和死亡原因，届时幸存男子的年龄将为63-67岁。我们与荷兰国防部和其他主要机构建立了合作协议，用于采样、追踪死亡和确定死因。我们的研究解决了两个研究问题：（1）产前饥饿暴露对63-67岁死亡率的影响是什么？我们将确定1944年11月至1946年3月出生在受饥荒影响最严重的六个城市的25，000名男子。男性将根据出生日期分类为在妊娠的不同阶段有饥饿暴露。作为没有产前饥荒暴露的对照组，我们将随机抽取10，000名出生在同一城市的男性，但在饥荒之前出生或在饥荒之后怀孕。(2)新的统计方法如何进一步完善现有的方法来评估产前饥荒暴露的长期影响？我们将使用功能数据分析纳入整个妊娠期平均每周热量配给的信息，以模拟18岁时食物配给变化对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，可以量化产前环境对国家出生队列中63-67岁死亡率的作用，并由国家登记处提供完整的死亡日期和原因。饥荒出生队列现在已经到了死亡率迅速增加的年龄，提供了极好的研究能力来检测产前饥荒对生存的即使是适度的影响（风险比~1.2）。饥荒的情况提供了一个准实验模型，以研究人类胎儿环境在特定妊娠期的深刻变化。荷兰的饥荒已经使公众健康了解了人类产前环境变化的长期影响，而且在未来有巨大的潜力这样做 我们将研究产前饥饿暴露对63-67岁死亡率的影响。我们将使用1944年11月至1946年3月期间出生在荷兰受严重战时饥荒影响最严重的六个城市的25，000名男性的研究记录。男性将按出生日期和地点分类，在妊娠的不同阶段遭受饥荒。将从没有产前饥饿暴露的男性中选择10，000名研究对照，并将比较在不同妊娠期暴露的男性的死亡日期和原因。研究结果将适用于世界各地的许多环境。

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.