Maternal Obesity and Weight Change in Neurobehavioral Development

母亲肥胖和体重变化对神经行为发育的影响

基本信息

批准号：
9133094
负责人：
CATHERINE A VANDEVOORT
金额：
$ 51.26万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2020-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9133094
关键词：
Address Adipocytes Adult American Autistic Disorder Behavior Biological Biological Markers Biometry Body Weight Changes Brain Cerebral cortex Characteristics Child Childhood Chronic Clinical Cognition Cognitive Conceptions Congresses DNA Methylation Development Developmental Delay Disorders Diabetes Mellitus Dyslipidemias Eating Effectiveness Employee Strikes Environment Epidemic Epigenetic Process Exposure to Fetal Development Functional disorder Genetic Risk Gynecologist Health Health Personnel Hippocampus (Brain)Histologic Histology Human Hyperglycemia Hypertension Immune Immunology Impairment Infant Inflammation Inflammatory Injury Institute of Medicine (U.S.)Intervention Link Macaca mulatta Maps Maternal Health Metabolic Metabolism Methylation Modeling Modification Mothers Neurodevelopmental Impairment Obesity Outcome Outcome Study Overweight Oxidative Stress Perinatal Exposure Phenotype Physiological Physiology Placenta Placental Insufficiency Placentation Pravastatin Pre-Eclampsia Pregnancy Pregnant Women Preventive Primates Process Property Public Health Reproducibility Reproductive Physiology Research Research Personnel Resources Risk Risk Factors Third Pregnancy Trimester Time Weight Weight Gain Weight maintenance regimen Woman adipokines autism spectrum disorder chemokine cytokine experience fetal food restriction genome wide methylation genome-wide gestational weight gain healthy weight immune activation male metabolome metabolomics methylation biomarker methylome neurobehavioral neurodevelopment nonhuman primate nutrition obesity management offspring prevent racial disparity response social socioeconomic disparity weight maintenance

项目摘要

Non-heritable risk factors for autism spectrum disorder (ASD) and developmental delay (DD) include maternal conditions associated with metabolic dysregulation, most notably pre-pregnancy obesity, excessive gestational weight gain, and complications associated with poor metabolic health, including chronic and gestational forms of hypertension, diabetes and dyslipidemia. Obesity has reached epidemic proportions in the U.S., with more than half of pregnant women overweight or obese. Racial and socioeconomic disparities are profound. The proposed research plan will explore physiological characteristics of maternal obesity that may be involved in neurodevelopmental compromise in a non-human primate model. We will compare inflammatory and metabolic changes to the gestational milieu in obese and normal-weighted mothers, as well as histologic and epigenetic modifications to the placenta and infant brain. Additionally, we will evaluate the effectiveness of two maternal intervention strategies, gestational weight maintenance and daily administration of the pharmacologic agent pravastatin through pregnancy, in reversing the effects of maternal obesity on the maternal and placental environments. Weight management has been recommended by both the Institute of Medicine and the American Congress of Obstetricians and Gynecologists for management of obesity in pregnancy, and the pharmacological properties of pravastatin provide biological plausibility for its use in preventing the systemic, placental and fetal consequences of maternal obesity. This proposal strives to utilize fully the unique resources inherent in the third trimester rhesus monkey model to address this serious clinical problem with substantial public health impact. Our interdisciplinary team weaves the expertise of investigators with extensive collaborative experience in maternal health and fetal development, reproductive physiology, nutrition, immunology, epigenetics, metabolomics, lipomics, biostatistics and neurodevelopment in both humans and non-human primates. The specific aims of the project will: 1) explore the physiologic effects of maternal obesity that underlie neurodevelopmental impairment and 2) determine whether two interventional strategies will prevent the effects of maternal obesity. The outcome of these studies will have direct translational value by informing women and their health providers of the risks of maternal obesity to the developing brain and will provide information on preventive options to help obese women and their health care providers lessen risk for their babies.

自闭症谱系障碍 (ASD) 和发育迟缓 (DD) 的非遗传性危险因素包括母亲与代谢失调相关的病症，最明显的是孕前肥胖、妊娠过度体重增加以及与代谢健康状况不佳相关的并发症，包括慢性和妊娠形式高血压、糖尿病和血脂异常。肥胖在美国已达到流行病的程度，超过一半的孕妇超重或肥胖。种族和社会经济差异是巨大的。这拟议的研究计划将探索可能与以下因素有关的孕产妇肥胖的生理特征：非人类灵长类动物模型中的神经发育受损。我们将比较炎症和肥胖和正常体重母亲妊娠环境的代谢变化，以及组织学和胎盘和婴儿大脑的表观遗传修饰。此外，我们将评估两种方法的有效性孕产妇干预策略、妊娠体重维持和每日用药怀孕期间使用普伐他汀，可逆转母亲肥胖对母亲和胎盘的影响环境。体重管理已获得医学研究所和美国妇产科医师大会负责妊娠期肥胖管理，以及普伐他汀的药理学特性为其用于预防全身性、母亲肥胖对胎盘和胎儿的影响。本提案力求充分利用独特的妊娠晚期恒河猴模型固有的资源可以解决这一严重的临床问题重大公共卫生影响。我们的跨学科团队将研究人员的专业知识与在孕产妇健康和胎儿发育、生殖生理学、营养学、人类和人类的免疫学、表观遗传学、代谢组学、脂质组学、生物统计学和神经发育非人类灵长类动物。该项目的具体目标将： 1）探索产妇的生理影响肥胖是神经发育障碍的基础，2) 确定两种干预策略是否有效将防止母亲肥胖的影响。这些研究的结果将具有直接的转化价值向妇女及其保健提供者告知孕产妇肥胖对发育中的大脑和意志的风险提供有关预防方案的信息，以帮助肥胖妇女及其医疗保健提供者降低肥胖风险他们的孩子。