Growth and adiposity in newborns: the influence of prenatal DHA supplementation

新生儿生长和肥胖：产前补充 DHA 的影响

• 批准号: 10194481
• 负责人: Holly Renee Hull
• 金额: $ 57.41万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10194481
• 关键词: 7 year old; Academy; Adipocytes; Adipose tissue; Age; Age-Months; Animal Experimentation; Birth; Body Composition; Body measure procedure; Cell Differentiation process; Characteristics; Child; Childhood; Clinical Trials; Data; Deposition; Development; Diet; Disease; Docosahexaenoic Acids; Docosahexaenoic acid supplementation; Dose; Double-Blind Method; Drug or chemical Tissue Distribution; Dual-Energy X-Ray Absorptiometry; Enrollment; Exposure to; Family; Fatty acid glycerol esters; Female; Fetal Development; Follow-Up Studies; Gender; Gene Expression; Generations; Genes; Goals; Growth; Human; Infant; Intake; Knowledge; Lead; Life; Life Expectancy; Link; Measures; Medical Care Costs; Medicine; Metabolic Diseases; Mothers; Newborn Infant; Nutrient; Obesity; Observational Study; Omega-3 Fatty Acids; Overweight; Parents; Phase; Phenotype; Placebos; Polyunsaturated Fatty Acids; Pregnancy; Pregnant Women; Premature Birth; Prevalence; Randomized; Recommendation; Regulation; Research Design; Severity of illness; Supplementation; Testing; Visceral; Weight Gain; Woman; adipocyte differentiation; base; cohort; critical period; disorder risk; effective intervention; efficacy testing; evidence based guidelines; experience; fatty acid metabolism; fetal; gestational weight gain; improved; innovation; lipid biosynthesis; neonate; obesity in children; obesity risk; offspring; offspring obesity; overweight child; oxidation; prenatal; prenatal exposure; prenatal influence; prevent; programs; response; sexual dimorphism; therapeutic target

PROJECT SUMMARY/ABSTRACT The prevalence of childhood obesity has dramatically increased leading to the prediction of a rapid generational decline in life expectancy and to a surge in medical care costs. Offspring exposed to excessive gestational weight gain (GWG) have greater total fat mass (FM) and central adiposity in childhood and are more likely to be overweight or obese. Currently, 56% of pregnant women experience excessive GWG. In pregnancies that experience GWG, it is critical to understand factors that influence FM accumulation and direct adipose tissue (AT) distribution as these are important early drivers of obesity occurrence, disease risk, and severity of disease development. Polyunsaturated fatty acids (PUFA) influence adipocyte development and FM accrual in two ways: influencing cell differentiation and fatty acid metabolism regulation. Increased prenatal exposure to the n-3 fatty acid family, including docosahexaenoic acid (DHA), prevented adipocyte maturation and suppressed genes involved in lipogenesis and increased the expression of genes involved with β oxidation. The overall net effect was a decrease in AT deposition. Observational studies associate greater maternal DHA levels with lower offspring FM, visceral AT and greater fat-free mass in childhood. However, data are lacking from RCT studying a contemporary U.S. based cohort where DHA is prenatally supplemented and offspring fat accrual and distribution are directly measured. This study will take advantage of an ongoing Phase III randomized, double blinded, and placebo controlled U.S. based pregnancy cohort (R01 HD083292, ClinicalTrials.gov ID: NCT02626299) in which n=400 women will be randomized to either 1000 mg/day or 200 mg/day of DHA during pregnancy. The purpose of the follow-up study is to determine how the prenatal dose of DHA interacts with GWG to influence offspring FM accrual. Data are lacking that examine important moderators and potential therapeutic targets that influence offspring growth and body composition changes during a critical period of the first 1,000 days suggested to be significant for programming the offspring phenotype. To develop effective interventions, it is important to understand nutrients that may protect against an offspring phenotype related to metabolic disease risk. Observational evidence in humans and basic animal research suggest that DHA, a nutrient generally low in the diet of US women, could be such a nutrient. This project is innovative, capitalizing on a large, ongoing, RCT of high and low-dose DHA supplementation of U.S. pregnant women, testing the efficacy of DHA supplementation in women with excessive GWG, and using direct measures of body composition (DXA). This data will inform the gap in knowledge regarding the impact of high levels of prenatal DHA supplementation on programming offspring FM accrual. The proposal will help identify the need for new recommendations for prenatal DHA supplementation by our National Academy of Medicine (DHA is not recognized in the US as an essential nutrient) and lead to evidence-based guidelines for DHA supplementation during pregnancy where none currently exist.

项目摘要/摘要 儿童肥胖症的流行率急剧上升，这导致了 预期寿命的代际下降和医疗费用的激增是造成这种现象的原因。暴露在过量环境中的后代 妊娠期体重增加(GWG)在儿童时期有更大的总脂肪质量(FM)和中心性肥胖，并且 更有可能超重或肥胖。目前，56%的孕妇GWG过高。在……里面 妊娠经历GWG，关键是要了解影响FM堆积和直接 脂肪组织(AT)分布，因为它们是肥胖发生、疾病风险和 疾病发展的严重性。多不饱和脂肪酸对脂肪细胞发育和FM的影响 通过两种方式产生作用：影响细胞分化和调节脂肪酸代谢。胎儿期增加 接触n-3脂肪酸家族，包括二十二碳六烯酸(DHA)，会阻止脂肪细胞成熟 抑制脂肪生成相关基因，增加β相关基因表达 氧化。总体的净影响是AT沉积的减少。观察性研究将更大的 儿童时期母体DHA水平与子代FM、内脏AT和较大的脱脂质量有关。然而， 从RCT研究当代美国队列中缺乏数据，在这些队列中，产前补充了DHA 并直接测量子代脂肪的积累和分布。这项研究将利用正在进行的 第三阶段随机、双盲、安慰剂对照的美国妊娠队列(R01 HD083292， ClinicalTrials.gov ID：NCT02626299)，其中n=400名女性将被随机分为1000 mg/天或200 mg/天 孕期服用DHA毫克/天。随访研究的目的是确定产前剂量是如何 DHA与GWG相互作用，影响后代的FM累积量。缺乏重要的数据来检验 影响后代生长和身体成分变化的调节剂和潜在治疗靶点 在最初1,000天的关键时期内，这对规划后代是很重要的 表型。要制定有效的干预措施，重要的是要了解可能预防疾病的营养物质 一种与代谢性疾病风险相关的后代表型。在人类和基本动物中的观察证据 研究表明，DHA，一种在美国女性饮食中普遍较低的营养物质，可能就是这样的营养物质。这 该项目是创新的，利用了美国高剂量和低剂量DHA补充的大规模、持续的RCT。 孕妇，测试补充DHA对GWG过多的妇女的疗效，并直接使用 身体成分测量(DXA)。这一数据将告知有关HIGH影响的知识差距 产前补充DHA水平对子代调频应计利润的影响该提案将有助于确定 我国国家医学科学院对产前补充DHA的新建议的必要性 (DHA在美国不被承认为必需营养素)，并导致DHA的循证指南 在怀孕期间补充，但目前没有补充。