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: 9119029
• 负责人: Nicole Renee Bush
• 金额: $ 65.76万
• 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/9119029
• 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; 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; cardiometabolic risk; cardiovascular disorder risk; cardiovascular risk factor; control trial; disorder risk; efficacy testing; fetal; follow-up; gestational weight gain; group intervention; improved; in utero; indexing; intergenerational; intervention effect; maternal stress; metabolic profile; neurobehavioral; novel; obesity risk; offspring; postnatal; prenatal; prenatal intervention; prenatal stress; prevent; programs; respiratory; transmission process; treatment group

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）：有效的一级预防需要了解可改变的疾病风险因素。肥胖、自主神经失调和 HPA 轴失调是心血管和代谢（心脏代谢）疾病的危险因素。它们在所有年龄段人群中的患病率都在增加，包括幼儿。一致的证据将心脏代谢风险的起源追溯到子宫内和产后早期，支持健康和疾病的发育规划的概念。母亲体重过重和压力过大正在成为影响后代发育的重要妊娠环境因素，并且可能导致后来的疾病。先前的研究主要是横断面或回顾性的和/或评估了有限的产前影响系统。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，以减少孕产妇的负担。 妊娠期间的压力和体重过度增加，以检查宫内暴露对随后儿童心脏代谢风险的影响。我们建议对试验中的 168 名女性后代从出生到 4 岁进行跟踪，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。我们将评估干预措施（目标 1）的影响，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，这些结局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产前的影响与产后的影响区分开来，并检查重要的发育轨迹；对其他暴露的评估将减少混杂因素，并提供有关干预途径和进一步目标的线索。产前干预的初步数据表明，它可以减轻母亲的压力和体重增加，而我们的后代试点研究的数据为我们的假设提供了初步支持，表明母亲压力和体重增加的改善预示着后代肥胖和神经行为调节指数的改善。具体目标是：1) 测试干预组中母亲所生的后代相对于对照组的后代，在出生时和生命的前 4 年是否具有更有利的心脏代谢结果（较低水平：肥胖、自主神经失调和 HPA 轴失调）。 2) 检查 168 名母婴二人组的全部样本（控制治疗组）是否： a) 出生时和生命前 4 年的心脏代谢风险结果对于妊娠期间肥胖和/或压力较大的母亲的后代更为不利。 b) 体重和压力水平较高的母亲所生的后代的不良心脏代谢结果会加剧（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相互作用尚未在人体研究中得到测试。