Effects of prenatal stress exposure on childhood physical and metabolic outcomes

描述(由申请人提供)：怀孕期间暴露在高水平的压力下会影响后代的认知、行为和身体发育。这被认为反映了母体应激激素的影响，这种荷尔蒙可以穿过胎盘，扰乱胎儿发育。产前应激暴露可能是健康与疾病发育起源的中介机制之一，这表明早期环境对成人健康具有终生影响。产前应激暴露与不良的出生结局有关，这增加了后来患慢性病的风险。动物和一些人类研究也表明，产前应激暴露与后来的心脏代谢疾病有关，如胰岛素抵抗和肥胖，与出生时的大小无关，这可能反映了应激激素对参与新陈代谢的发育中的HPA(下丘脑-垂体-肾上腺)轴的影响。然而，人类对产前应激的研究很难设计，而且我们关于儿童和青春期产前应激的生理和代谢结果的数据有限，这些结果可能是成人疾病发生之前的。我的目标是研究产前应激暴露对120名青少年的身体发育和代谢模式的影响，这些青少年的母亲在1998年因一场严重的冰暴而在怀孕期间受到压力，还有262名幼儿的母亲在2008年的一场洪水中怀孕。这些儿童已经参加了两项产前应激暴露的前瞻性纵向研究的定期评估：冰暴项目和爱荷华州洪水研究。这些研究包括出生时的体型测量和儿童时期的一些人体测量；对母亲压力暴露的详细评估；以及关于潜在混杂变量的数据，如社会经济状况、母亲的特质焦虑和怀孕期间发生的其他应激性生活事件。这两项研究中的孩子都参加了定期评估，在此期间我可以收集额外的数据。方法：我将利用已有的数据分析两个队列中产前应激暴露对出生结局(出生体重、身高和胎龄头围)的影响。我将收集爱荷华州21/2岁的洪水研究参与者和131/2岁的冰暴计划参与者的详细人体测量数据(身高；体重；腰围、臀围、上臂中部和小腿围；以及三头肌、肩胛骨下和髂上皮褶)。控制混杂变量，我将研究压力暴露水平与身体大小、瘦肌肉和脂肪质量以及脂肪分布模式之间的关系。我还将使用在冰暴计划中收集的身高和体重的纵向测量来分析产前应激暴露是否以及如何影响从出生到青春期的生长轨迹。最后，我将测量冰暴计划参与者的空腹血糖和胰岛素水平，并分析它们与产前应激水平的关系。这些独特的数据有助于解决关于健康和疾病的发育起源的悬而未决的问题，并将突出未来研究的许多领域。

DESCRIPTION (provided by applicant): Exposure to high levels of stress during pregnancy can impact offspring cognitive, behavioral, and physical development. This is thought to reflect the effects of maternal stress hormones, which can cross the placenta and disrupt fetal development. Prenatal stress exposure might represent one of the mediating mechanisms in the Developmental Origins of Health and Disease, which suggests that the early environment holds lifelong implications for adult health. Prenatal stress exposure has been associated with poor birth outcomes, which increases risk for later chronic diseases. Animal and some human studies also suggest that prenatal stress exposure is associated with later cardiometabolic diseases such as insulin resistance and obesity independently of size at birth, perhaps reflecting effects of stress hormones on the developing HPA (hypothalamic pituitary adrenal) axis, which is involved in metabolism. However, human studies of prenatal stress are difficult to design, and we have limited data about physical and metabolic outcomes of prenatal stress in childhood and adolescence that might precede the development of adult disease. My Objective is to examine the effects of prenatal stress exposure on physical growth and metabolic patterns among 120 adolescents whose mothers were exposed to stress during pregnancy due to a severe ice storm in 1998; and among 262 toddlers whose mothers were pregnant during a flood in 2008. These children are already participating in regular assessments for two prospective longitudinal studies of prenatal stress exposure: Project Ice Storm and the Iowa Flood Study. The studies include measurements of size at birth and some anthropometric measurements in childhood; detailed assessments of maternal stress exposure; and data on potential confounding variables such as socioeconomic status, maternal trait anxiety, and other stressful life events occurring during pregnancy. The children in both studies participate in regular assessments during which I can collect additional data. Methods: I will analyze the effects of prenatal stress exposure on birth outcomes (birth weight, stature, and head circumference for gestational age) in both cohorts using already available data. I will collect detailed anthropometric measurements (height; weight; waist, hip, mid-upper-arm, and calf circumference; and triceps, subscapular, and suprailiac skinfolds) among Iowa Flood Study participants at age 21/2, and Project Ice Storm participants at age 131/2. Controlling for confounding variables, I will examine relationships between level of stress exposure and body size, lean muscle and fat mass, and fat distribution patterns. I will also use longitudinal measures of height and weight collected in Project Ice Storm to analyze if and how prenatal stress exposure impacts growth trajectories from birth to adolescence. Finally, I will measure fasting glucose and insulin levels for Project Ice Storm participants and analyze their relationship to prenatal stress levels. These unique data can help address unanswered questions about the developmental origins of health and disease, and will highlight many areas for future research.