Effects of prenatal stress exposure on childhood physical and metabolic outcomes

描述（由申请人提供）：怀孕期间暴露于高水平的压力会影响后代的认知、行为和身体发育。这被认为反映了母体应激激素的影响，这种激素可以穿过胎盘，破坏胎儿的发育。产前压力暴露可能是健康和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身影响。产前压力暴露与不良的分娩结果有关，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（如胰岛素抵抗和肥胖）有关，而与出生时的体型无关，这可能反映了应激激素对发育中的下丘脑-垂体-肾上腺轴（HPA）的影响，该轴参与代谢。然而，产前压力的人体研究很难设计，而且我们关于儿童和青少年产前压力可能先于成人疾病发展的身体和代谢结果的数据有限。我的目的是检查产前压力暴露对120名青少年的身体生长和代谢模式的影响，这些青少年的母亲在怀孕期间因1998年严重的冰暴而暴露于压力；在262名幼儿中，他们的母亲在2008年洪水期间怀孕。这些孩子已经参加了两项关于产前压力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尺寸测量和儿童时期的一些人体测量；产妇压力暴露的详细评估；以及潜在的混杂变量数据，如社会经济地位，母亲特质焦虑，以及怀孕期间发生的其他压力生活事件。两项研究中的孩子都参加了定期的评估，在此期间我可以收集额外的数据。方法：我将分析产前应激暴露对出生结果的影响（出生体重，身高，胎龄头围）在两个队列中使用已有的数据。我将收集爱荷华州洪水研究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、三头肌、肩胛下和髌上皮肤皱褶），以及冰风暴项目参与者的131/2岁。控制混杂变量，我将检查压力暴露水平与体型、瘦肌肉和脂肪量以及脂肪分布模式之间的关系。我还将使用冰暴项目中收集的身高和体重的纵向测量来分析产前压力暴露是否以及如何影响从出生到青春期的生长轨迹。最后，我将测量冰风暴项目参与者的空腹血糖和胰岛素水平，并分析它们与产前压力水平的关系。这些独特的数据可以帮助解决关于健康和疾病的发育起源的未解之谜，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.