PreNatal Nutrition and Adult Disease

出生体重下降，特别是由于宫内生长迟缓，与心血管疾病的风险增加以及胰岛素抵抗、2型糖尿病和高血压的患病率增加有关。有人提出，胎儿营养不良可能导致胎儿“程序化”，从而增加日后罹患某些疾病的风险。具体的暴露，包括产妇营养的任何潜在作用，尚未确定。迄今为止，还没有一项具有适当偏倚控制的研究表明，孕期改变的母体营养可以诱导胎儿编程。更具体地说，还没有很好地确定孕妇营养不良可能导致胎儿编程的任何关键时期。因此，所报告的出生时体型与成人慢性病风险之间的关联可能反映了非营养暴露、社会阶层或其他因素的混杂。我们建议通过一项研究来解决这些问题，研究孕妇在怀孕三个月营养不良，以及随后的胰岛素抵抗、2型糖尿病、高血压、肥胖和成年后冠状动脉疾病的其他危险因素。我们将研究(1)胎儿编程是否可以由孕妇营养不良引起，(2)编程仅限于妊娠的特定阶段，以及(3)任何影响在所检查的心血管疾病危险因素中是一致的。我们也将评估敏感性和特异性选择形态学措施的手作为标记的时间宫内暴露。这项研究在荷兰的独特环境中是可行的，在荷兰，选择了在产前暴露于1944-45年荷兰饥荒的男性和女性，他们现在55-60岁，可以被识别、追踪和检查。我们将研究约400名在预先指定的怀孕阶段有产前饥荒暴露的先证者，200名没有产前饥荒暴露的先证者，以及一个未暴露的同性兄弟姐妹作为每个先证者的对照。研究的总规模约为1200人。饥荒的独特环境和对兄弟姐妹配对设计的新颖使用，提供了一种良好控制的评估，可以评估母亲在怀孕特定阶段营养不良对其婴儿日后患病风险的影响。我们将确定所报道的出生体重和心血管疾病风险之间的关联在多大程度上反映了母亲共同的营养暴露。这些尚未解决的问题的答案对于进一步有针对性地研究人类胎儿编程机制至关重要。

Decreased birth weight, especially if due to intrauterine growth retardation, is associated with increased risk for cardiovascular disease and increased prevalence of insulin resistance, Type 2 diabetes mellitus, and hypertension. It has been proposed that fetal undernutrition may result in 'programming' of the fetus and thereby increase the risk for selected diseases later in life. The specific exposures, including any potential role of maternal nutrition, have not been determined. To date, no study with adequate bias control has showed that altered maternal nutrition in pregnancy can induce fetal programming. More specifically, any critical time periods in pregnancy during which maternal undernutrition could induce fetal programming have not been well established. It is therefore possible that the reported associations that are seen between size at birth and adult chronic disease risk may reflect confounding by a non-nutritional exposure, by social class, or by other factors. We propose to address these issues in a study of maternal undernutrition in identified trimesters of pregnancy and the subsequent risk of insulin resistance, Type 2 diabetes mellitus, hypertension, obesity and other risk factors for coronary artery disease in adulthood. We will examine whether (1) fetal programming can be induced by maternal undernutrition in pregnancy, (2) programming is limited to specific stages of gestation and (3) any effects are consistent across the examined cardiovascular disease risk factors. We will also evaluate the sensitivity and specificity of selected morphological measures of the hand as markers of the timing of intrauterine exposure. This study is feasible in the unique setting of the Netherlands, where selected men and women who were exposed prenatally to the Dutch famine of 1944-45 and who are now 55-60 years old can be identified, traced, and examined. We will study about 400 probands with prenatal famine exposure at pre-specified stages of pregnancy, 200 probands without prenatal famine exposure, and an unexposed same-sex sibling serving as a control for each proband. The total study size will be about 1,200 individuals. The unique circumstances of the famine and the novel use of a sib-paired design provide a well controlled assessment of the effect of maternal undernutrition at specific stages in pregnancy on her infant's disease risk later in life. We will establish the degree to which reported associations between birth weight and cardiovascular disease risk could reflect a shared maternal nutritional exposure. Answers to these unresolved issues are essential for further targeted studies into the mechanism of fetal programming in humans.