Pre Natal Nutrition and Adult Disease

出生体重降低，特别是由于胎儿宫内发育迟缓，会增加心血管疾病的风险，增加胰岛素抵抗、2型糖尿病和高血压的患病率。有人提出，胎儿营养不良可能会导致胎儿“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。到目前为止，还没有足够的偏向对照研究表明，孕妇在怀孕期间改变营养可以诱导胎儿程序化。更具体地说，在怀孕期间，母亲营养不良可能导致胎儿程序化的关键时期尚未得到很好的确定。因此，报告的出生体型和成人慢性病风险之间的关联可能反映了非营养性暴露、社会阶层或其他因素的混淆。我们建议在一项关于妊娠三个月孕妇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的研究中解决这些问题。我们将检查(1)妊娠期间母亲营养不良是否会导致胎儿程序化，(2)程序化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都是一致的。我们还将评估选定的手部形态测量作为宫内暴露时间的标记物的敏感性和特异性。这项研究在荷兰的独特环境下是可行的，在那里，可以识别、追踪和检查选定的出生前暴露于1944-45年荷兰饥荒的男性和女性，他们现在55-60岁。我们将研究大约400名在怀孕前特定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，以及作为每个先证者的对照的未暴露的同性兄弟姐妹。研究的总规模约为1,200人。饥荒的独特情况和姐妹配对设计的新颖使用，提供了对怀孕特定阶段母亲营养不良对婴儿日后疾病风险的影响的良好控制的评估。我们将确定报告的出生体重和心血管疾病风险之间的关联在多大程度上可以反映母亲共同的营养暴露。这些悬而未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的机制是至关重要的。

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.