Preventing Inter-generational Transmission of Obesity and Cardiometabolic Risk

预防肥胖和心脏代谢风险的代际传播

• 批准号: 8528402
• 负责人: Nicole Renee Bush
• 金额: $ 68.3万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8528402
• 关键词: 4 year old; Address; Affect; Age; Animal Model; Autonomic nervous system; Back; Birth; Cardiovascular system; Cell physiology; Child; Clinical; Control Groups; Data; Development; Diet; Disease; Disease susceptibility; Eating; Environment; Epidemiology; Evaluation; Health; Human; Hydrocortisone; Hyperactive behavior; Individual; Infant; Insulin Resistance; Intervention; Intervention Trial; Knowledge; Lead; Life; Malnutrition; Metabolic; Metabolic Diseases; Mothers; Newborn Infant; Obesity; Organism; Outcome; Pathway interactions; Physiological; Pilot Projects; Play; Population; Pregnancy; Prevalence; Prevention; Primary Prevention; Process; Regulation; Relative (related person); Research; Risk; Risk Factors; Role; Sampling; Sinus Arrhythmia; Societies; Stress; Structure; Sum; System; Testing; Time; Tissues; Treatment Efficacy; Variant; Weight; Weight Gain; Woman; body system; burden of illness; cardiovascular disorder risk; cardiovascular risk factor; control trial; disorder risk; efficacy testing; fetal; follow-up; group intervention; improved; in utero; indexing; intergenerational; intervention effect; maternal stress; neurobehavioral; novel; offspring; postnatal; prenatal; prenatal intervention; prenatal stress; prevent; programs; public health relevance; respiratory; transmission process

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.

描述（由申请人提供）：有效的初级预防需要了解可修改的疾病风险前因。肥胖，自主性失调和HPA轴功能障碍是心血管和代谢（心脏代谢）疾病的危险因素。在所有年龄段的人口中，包括幼儿在内的人口越来越多。融合证据将心脏代谢风险的起源追溯到宫内和产后早期生命时期，支持健康和疾病的发展概念。母体过多的体重和过度的压力暴露正作为影响后代发展的重要妊娠环境因素，并且是后来疾病的合理贡献者。先前的研究主要是横截面或回顾性和/或评估了有限的产前效应系统。拟议的研究通过利用产前干预的现有控制试验来扩展这项研究，以减少母亲 妊娠期间的压力和体重增加过多，以检查宫内暴露对随后儿童心脏代谢风险的影响。我们建议从出生到4岁的试验中追踪168名妇女后代，并对心脏代谢危险因素（肥胖，自主和HPA轴失调）及其发育轨迹进行纵向评估。我们将评估干预措施的影响（AIM 1），以及个体水平变异对产前压力和体重增加的影响（AIM 2）对可能是心血管疾病风险的早期驱动因素的新生儿和儿童结局的影响。评估的跨度使我们能够将产前的影响与产后影响分开，并检查重要的发展轨迹；评估其他暴露将减少混杂并提供有关途径和进一步干预目标的线索。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，而我们后代试验研究的数据为我们的假设提供了初步支持，显示了母体的改善压力和体重增加预测的后代肥胖和神经行为的指标改善了指标。具体目的是：1）测试母亲在干预措施中出生的后代是否在出生的前四年中，在出生和出生的前四年中，是否具有更有利的心脏代谢结果（脂肪，肥胖，自主性失调和HPA轴失调），相对于对照组的后代。 2）检查整个168个母亲二元组（控制治疗组）是否：a）在出生时和生命的前4年中，心脏代谢风险结果在妊娠期间具有更大肥胖和/或压力的母亲的后代更加不利。 b）在体重和压力较高的母亲（协同作用）的母亲的后代中，不良心脏代谢结果得到了增强。动物模型为此类关联提供了支持，但是在人类研究中尚未测试这种对后代心脏代谢风险结果的互动作用。