Prenatal Under Nutrition and Mortality Through Age 63 Project

描述(申请人提供)：在1944-1945年的荷兰饥荒期间，每天提供900大卡的救济口粮。我们将通过将1944-1947年出生的男性的军事检查记录与死亡记录联系起来，来检验这种紧张的胎儿环境是否对成年人的存活有重大影响。我们将在2010年前确定生命状况和死因，届时幸存男子的年龄将为63-67岁。我们已经与荷兰国防部和其他主要机构就抽样、死亡追踪和确定死因达成了合作协议。我们的研究解决了两个研究问题：(1)产前饥荒暴露对63-67岁的死亡率有什么影响？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名男性。男性将根据出生日期被归类为在怀孕不同阶段暴露于饥荒。作为对照，我们将随机抽取10,000名出生在相同城市、但在饥荒之前出生或在饥荒后怀孕的男性作为对照，不进行产前饥荒暴露。(2)新的统计方法如何进一步改进评估产前饥荒暴露的长期影响的现有方法？我们将使用功能数据分析来纳入整个妊娠期平均每周卡路里配给的信息，以模拟食物配给的变化对18岁时选定特征以及随后所有原因和特定原因死亡率的影响。这是一个独特的机会，可以量化出生前环境对全国出生队列中63-67岁的死亡率的作用，并完全确定国家登记所提供的死亡日期和原因。饥荒出生人群现在已经达到了死亡率迅速上升的年龄，这为研究提供了极好的研究能力，可以检测到即使是轻微的产前饥荒对生存的影响(风险比约为1.2)。饥荒的情况为研究特定孕期人类胎儿环境的深刻变化提供了一个准实验模型。荷兰饥荒已经向公众健康通报了人类产前环境变化的长期影响，并在未来具有巨大的潜力。 我们将研究产前饥荒暴露对63-67岁年龄段死亡率的影响。我们将使用在1944年11月至1946年3月期间出生的25,000名男性的研究记录，这些男性出生在荷兰受严重战争时期饥荒影响最严重的六个城市。男性将根据出生日期和地点被归类为在怀孕不同阶段遭受饥荒的男性。1万名研究控制组将从没有产前饥荒暴露的男性中挑选出来，并将比较不同怀孕三个月中暴露于饥荒中的男性的死亡日期和死因。这项研究结果将在世界各地的许多环境中发挥作用。

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.