Preventing Inter-generational Transmission of Obesity and Cardiometabolic Risk

描述(由申请人提供)：有效的初级预防需要了解疾病风险的可改变的前因。肥胖、自主神经失调和HPA轴失调是心血管和代谢(心脏代谢)紊乱的危险因素。它们在所有年龄段的人群中的流行率都在增加，包括在幼儿中。越来越多的证据将心脏代谢风险的起源追溯到宫内和出生后早期，支持健康和疾病发展规划的概念。孕妇超重和过度应激暴露正在成为影响后代发育的重要妊娠环境因素，并可能导致后来的疾病。以前的研究主要是横断面或回溯性的，和/或评估了有限的系统对产前的影响。这项拟议的研究通过利用现有的产前干预对照试验来扩展这项研究，以减少孕产妇 妊娠期间的压力和过度体重增加，以检查宫内暴露对随后儿童心脏代谢风险的影响。我们建议在试验中跟踪168名妇女的后代，从出生到4岁，对心脏代谢危险因素(肥胖、自主神经和HPA轴失调)及其发育轨迹进行纵向评估。我们将评估干预的效果(目标1)，以及产前压力和体重增加的个体水平差异(目标2)对新生儿和儿童结局的影响，这些结果可能是心血管疾病风险的早期驱动因素。评估的跨度使我们能够将出生前和出生后的影响分开，并检查重要的发育轨迹；而对其他暴露的评估将减少混淆，并提供关于干预途径和进一步目标的线索。来自产前干预的初步数据表明，它可以减少母亲的压力和体重增加，我们的子代试点研究的数据为我们的假设提供了初步支持，表明母亲在压力和体重增加方面的改善预示着子代肥胖指数和神经行为调节的改善。具体目的是：1)测试干预中母亲所生的孩子在出生时和出生后头4年是否比对照组的孩子有更有利的心脏代谢结果(较低水平的肥胖、自主神经失调和HPA轴失调)。2)对168名母婴双胞胎的全部样本(对照组)进行检查：a)出生时和出生后头4年，肥胖和/或孕期压力较大的母亲所生子女的心脏代谢风险结果是否更不利。B)体重和压力水平较高的母亲所生子女的心脏代谢不良结局更高(协同效应)。动物模型为这种关联提供了支持，但这种对后代心脏代谢风险结果的交互影响尚未在人类研究中得到测试。

DESCRIPTION (provided by applicant): Effective primary prevention requires knowledge of modifiable antecedents of disease risk. Obesity, autonomic dysregulation, and HPA axis dysregulation are risk factors for cardiovascular and metabolic (cardiometabolic) disorders. Their prevalence in populations of all ages is increasing, including among young children. Converging evidence traces the origins of cardiometabolic risk back to the intrauterine and early postnatal period of life, supporting the concept of developmental programming of health and disease. Maternal excess weight and excess stress exposure are emerging as important gestational environment factors that affect offspring development and are plausible contributors to later disease. Previous research has been primarily cross-sectional or retrospective and/or has assessed limited systems for prenatal effects. The proposed research expands this research by capitalizing on an existing control trial of a prenatal intervention to reduce maternal stress and excessive weight gain during gestation to examine the effects of intrauterine exposures on subsequent child cardiometabolic risk. We propose to follow 168 offspring of women in the trial from birth until 4 years age, with longitudinal assessments of cardiometabolic risk factors (adiposity, autonomic and HPA axis dysregulation) and their developmental trajectories. We will evaluate the effects of the intervention (Aim 1), as well as the effects of individual-level variation in prenatal stress and weight gain (Aim 2), on newborn and child outcomes that are likely early drivers of cardiovascular disease risk. The span of assessments allows us to separate the effects of prenatal from postnatal influences and examine important developmental trajectories; and assessment of other exposures will reduce confounding and provide clues about pathways and further targets of intervention. Preliminary data from the prenatal intervention suggest it reduces stress and weight gain in mothers and data from our offspring pilot study provide initial support for our hypotheses, showing maternal improvements in stress and weight gain predicted improved indices of offspring adiposity and neurobehavioral regulation. The SPECIFIC AIMS are to: 1) Test whether offspring born to mothers in the intervention have more favorable cardiometabolic outcomes (lower levels of: adiposity, autonomic dysregulation, and HPA-axis dysregulation) at birth and over the first 4 years of life, relative to offspring in the control group. 2) Examine across the full sample of 168 mother-infant dyads (controlling for treatment group) whether: a) Cardiometabolic risk outcomes, at birth and over the first 4 years of life, are more adverse in offspring from mothers with greater adiposity and/or stress during pregnancy. b) Adverse cardiometabolic outcomes are heightened in offspring from mothers with higher levels of both weight and stress (synergistic effects). Animal models provide support for such associations, but this interactive effect on offspring cardiometabolic risk outcomes has not yet been tested in human studies.