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: 9751854
• 负责人: Holly Renee Hull
• 金额: $ 57.48万
• 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/9751854
• 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; Childhood Overweight; Clinical Trials; Data; Deposition; Development; Diet; Disease; Docosahexaenoic Acids; 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; 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.

项目总结/摘要 儿童肥胖症的患病率急剧增加，导致预测儿童肥胖症的快速增长。 预期寿命的世代下降和医疗保健费用的激增。后代暴露于过量的 妊娠期体重增加（GWG）在儿童期有更大的总脂肪量（FM）和中心性肥胖， 更有可能超重或肥胖。目前，56%的孕妇经历过过量的GWG。在 怀孕经历GWG，关键是要了解影响FM积累和直接 脂肪组织（AT）分布，因为这些是肥胖发生、疾病风险和 疾病发展的严重程度。多不饱和脂肪酸（PUFA）影响脂肪细胞发育和FM 脂肪酸的积累主要通过两种途径：影响细胞分化和调节脂肪酸代谢。产前增加 暴露于n-3脂肪酸家族，包括二十二碳六烯酸（DHA），阻止脂肪细胞成熟 抑制脂肪生成相关基因的表达，增加β-淀粉样蛋白相关基因的表达， 氧化总体净效应是AT沉积减少。观察性研究显示， 母亲的DHA水平与较低的后代FM，内脏AT和更大的无脂肪质量在儿童时期。然而，在这方面， 缺乏来自研究当代美国队列的随机对照试验的数据，该队列在产前补充DHA 并且直接测量后代脂肪积累和分布。这项研究将利用正在进行的 III期随机、双盲和安慰剂对照的美国妊娠队列（R 01 HD 083292， ClinicalTrials.gov ID：NCT 02626299），其中n=400名女性将随机接受1000 mg/天或200 mg/天 怀孕期间每天摄入100毫克DHA。后续研究的目的是确定产前剂量的 DHA与GWG相互作用影响后代FM的增加。缺乏数据来检查重要的 影响后代生长和身体组成变化的调节剂和潜在治疗靶点 在前1,000天的关键时期，这对后代的编程至关重要。 表型为了制定有效的干预措施，重要的是要了解营养素， 与代谢性疾病风险相关的后代表型。人类和基础动物的观察证据 研究表明，DHA，一种在美国女性饮食中含量通常较低的营养素，可能就是这样一种营养素。这 该项目是创新的，利用了一个大型的，正在进行的，高剂量和低剂量DHA补充剂的随机对照试验， 孕妇，测试DHA补充剂在GWG过量的妇女中的功效，并直接使用 身体成分（DXA）。这些数据将说明关于高风险影响的知识方面的差距。 产前DHA补充水平对后代FM增加的影响。该提案将有助于确定 我们的国家医学科学院需要对产前DHA补充提出新的建议 (DHA在美国不被认为是一种必需营养素），并导致DHA的循证指南 在怀孕期间补充，目前还没有。