Preconception Maternal Nutrition, Offspring DNA Methylation, and InfantGrowth in Low Resource Settings

资源匮乏环境下的孕前孕产妇营养、后代 DNA 甲基化和婴儿生长

• 批准号: 10838014
• 负责人: Sarah Jean Borengasser
• 金额: $ 58.24万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10838014
• 关键词: Acceleration; Administrative Supplement; Age; Anthropometry; Birth; Birth length; Child; Chronic; Climate; Conceptions; Country; DNA Methylation; Data; Developing Countries; Epigenetic Process; Exposure to; Fetal Growth; First Pregnancy Trimester; Goals; Growth; Guatemala; Head circumference; Health Benefit; Heat Stress Disorders; India; Infant; Life; Link; Maps; Modification; Mothers; Neonatal; Nutritional; Nutritional status; Outcome; Pakistan; Parents; Poverty; Pregnancy; Pregnant Women; Randomized; Randomized, Controlled Trials; Resolution; Resource-limited setting; Site; Supplementation; Temperature; Testing; Woman; Work; climate change; dietary supplements; environmental change; epigenome; epigenome-wide association studies; fetal; global health; global temperature; health of the mother; improved; indexing; mother nutrition; nutrition; offspring; postnatal; spatiotemporal; thermal stress

ABSTRACT High ambient temperature and heat stress, closely linked to climate change are an imminent threat to the health of mothers and children globally. Chronic nutritional impoverishments already contribute to inadequate fetal and postnatal growth in many developing countries. The goal of this administrative supplement is to examine the double-burden of poor maternal nutrition and heat exposure by linking state-of-the-art thermal stress indicators, anthropometry, and epigenetics. Data from a multi-country randomized controlled trial (Women First, NCT01883193) revealed detrimental impact of excessive heat in the first trimester on birth length and head circumference of the infant in Pakistan, one of the four trial sites. This trial, which compared the effects of a comprehensive nutritional supplement (CNS) uncovered that impacts of heat on birth length were mitigated in women randomized to CNS suggesting potential interactions between heat and maternal nutritional status. This administrative supplement will conduct analysis of thermal stress indices among all sites of the WF trial (4 countries on 3 continents) integrating universal thermal climate index (UTCI) with existing longitudinal anthropometric data (from birth to 24 mo) and newly generated epigenetic data from the WF trial. Studies in Specific Aim 1 will examine associations between UTCI in mother-child dyads and neonatal/child outcomes from birth through 2 y of age and effect-modification by CNS supplementation. Using newly developed high-resolution spatiotemporal maps of UTCI derived from the ERA5-Land reanalysis (HiTiSEA), the studies will examine 1) associations between maternal heat stress and fetal growth in all sites (DRC, Guatemala, India and Pakistan, n= 2,442) from the WF trial; 2) associations between heat exposure and child growth in the first two years of life; and 3) examine interactions between heat and maternal CNS supplementation. In Specific Aim 2, we will examine the interaction between UTCI and nutritional status on placental (N = 463) and neonatal DNA methylation (buccal, 3 months, N = 391). Leveraging DNAme data generated in the parent R01, we will investigate associations between maternal heat exposure (UTCImax) in each trimester and targeted DNAme (metastable epialleles & epigenetic age acceleration) and an epigenome-wide association analysis. Collectively the proposed work will bridge critical gaps in our current understanding of how climate and environmental change adversely impact pregnant women and children, and the potential for nutrition to mitigate this burden.

抽象的 高环境温度和热应力，与气候变化紧密相关，这是对 全球母亲和儿童的健康。慢性营养贫困已经有助于不足 许多发展中国家的胎儿和产后增长。这种行政补充的目的是 通过连接最先进的热量，检查不良的母体营养和热暴露的双重负担 压力指标，人体测量法和表观遗传学。来自多国随机对照试验的数据 （妇女首先，NCT01883193）揭示了孕期过热对出生的有害影响 巴基斯坦婴儿的长度和头围，这是四个试验地点之一。该试验，比较 全面的营养补充剂（CNS）的影响发现热量对出生长度的影响 在随机分配给中枢神经系统的妇女中缓解了表明热量与母体之间的潜在相互作用 营养状况。这种管理补充剂将对所有人中的热应力指数进行分析 WF试验的地点（3大洲的4个国家）将通用热气候指数（UTCI）与 现有的纵向人体测量数据（从出生到24个月），并从 WF试验。特定目标1的研究将检查母子二元组中UTCI与 新生儿/儿童的结局从出生到2年的年龄和CNS补充效应修饰。 使用新开发的高分辨率时空图的UTCI的高分辨率时空图 （日开尼），研究将检查1）所有部位的母体热应激与胎儿生长之间的关联 （DRC，危地马拉，印度和巴基斯坦，n = 2,442）来自WF试验； 2）热暴露之间的关联 和儿童在生命的头两年中成长； 3）检查热量和母体中枢神经系统之间的相互作用 补充。在特定目标2中，我们将研究UTCI与营养状况之间的相互作用 胎盘（n = 463）和新生儿DNA甲基化（颊，3个月，n = 391）。利用DNAME数据 在母体R01中产生，我们将调查母体热暴露（UTCIMAX）中的关联 每个三个月和靶向dname（亚稳态和表观遗传年龄加速）和 全基因组整个关联分析。拟议的工作集体将弥合当前的关键差距 了解气候和环境变化如何不利影响孕妇和儿童， 以及营养减轻这种负担的潜力。