A Multidimensional Approach to Understanding Prenatal Health and Psychosocial Factors in Relation to the Maternal Inflammatory Milieu and Offspring Neurodevelopment

了解与母体炎症环境和后代神经发育相关的产前健康和心理社会因素的多维方法

• 批准号: 10607823
• 负责人: Madeleine Allen
• 金额: $ 4.77万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-20 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10607823
• 关键词: Address; Affect; Anti-Inflammatory Agents; Area; Awareness; Biological; Biology; Body Size; Body mass index; Brain; Cluster Analysis; Communications Media; Complex; Conceptions; Cytokine Network Pathway; Data Set; Development; Dimensions; Discipline of obstetrics; Endocrine; Environment; Experimental Designs; Goals; Health; Heterogeneity; Historical Demography; Immune; Individual; Inflammation; Inflammatory; Literature; Longevity; Maternal Health; Measures; Mental disorders; Methods; Multivariate Analysis; Nature; Neurosciences Research; Outcome; Participant; Pathway interactions; Pattern; Population; Pregnancy; Prenatal Nutrition; Principal Component Analysis; Psychological Stress; Psychopathology; Psychosocial Factor; Psychosocial Stress; Recording of previous events; Reproducibility; Research; Research Design; Risk; Risk Factors; Role; Science; Stress; Subgroup; Techniques; Training; Trauma; United States National Institutes of Health; Validation; Variant; Weight Gain; Work; cytokine; demographics; dimensional analysis; fetal; high dimensionality; inflammatory milieu; innovation; life history; longitudinal dataset; meetings; multidimensional data; neurobehavioral; neurodevelopment; nutrition; offspring; prenatal; prenatal health; prepregnancy; psychosocial; response; sociodemographics; statistics; systemic inflammatory response

PROJECT SUMMARY Preconceptional and prenatal psychological stress, demographics, trauma, health, and nutrition all have potential to alter offspring neurodevelopmental outcomes. These aspects of the prenatal environment are hypothesized to influence the developing fetal brain via stress-sensitive aspects of maternal-placental-fetal biology (MPF), such as immune and endocrine functioning. However, previous research has centered around univariate analyses that do not consider the wide array of preconceptional and prenatal factors with potential to influence MPF biology and the developing fetal brain. Given the highly complex and interactive nature of these relationships, multivariate analyses are well-suited to identify canonical patterns in high-dimensionality analyses that may shed light on potential inflammatory mechanisms by which the preconceptional and prenatal environment may influence offspring brain development. Inflammation may be best characterized by considering multiple cytokines at once, as they appear to act co-dependently—cytokines that frequently work together to communicate form cytokine networks. The use of cytokine networks has become an increasingly popular method of conceptualizing and analyzing inflammation, given that specific cytokine networks are associated with certain psychopathologies or heterogenous presentations of mental disorders. Further, specific cytokine networks during pregnancy have been associated with altered offspring neurodevelopmental outcomes. Furthermore, little to none of these studies have been reproduced in independent datasets. Given the increasing awareness of limited reproducibility in neuroscience research, there has been an urgent push, spearheaded by the NIH, towards rigorously designed experiments and increased reproducibility. The overall goal of the proposed study is to examine how multiple preconceptional and prenatal factors affect maternal systemic inflammation during pregnancy and associated alterations in offspring neurodevelopment, while meeting the need for greater rigor and reproducibility in an innovative study design which will replicate complex multivariate analyses across three high-dimensionality datasets. The specific aims of this proposal are: 1) Identify maternal psychosocial contributors to the maternal inflammatory milieu during pregnancy at a multivariate level; 2) Identify potent health indicators of the maternal inflammatory milieu during pregnancy at a multivariate level; 3) Identify subgroups of participants with distinct patterns of maternal systemic inflammation and examine potentially relevant interactions between health and psychosocial factors, as well as neurodevelopmental outcomes associated with each cluster. This proposal intends to innovatively analyze cytokine network activity as a potential pathway by which aspects of the preconceptional and prenatal environment alter offspring neurodevelopment using multivariate statistical techniques. Additionally, given frequent challenges with reproducibility in science, results from the analyses will be cross validated across three independent datasets.

项目概要 孕前和产前心理压力、人口统计、创伤、健康和营养都有潜力 改变后代神经发育结果的产前环境的这些方面已被推向市场。 通过母体-胎盘-胎儿生物学（MPF）的压力敏感方面影响胎儿大脑的发育， 例如免疫和内分泌功能然而，之前的研究主要集中在单变量上。 分析未考虑可能影响的各种孕前和产前因素 鉴于这些的高度复杂性和交互性，MPF 生物学和发育中的胎儿大脑。 关系，多变量分析非常适合识别高维分析中的规范模式 这可能揭示潜在的炎症机制，通过该机制，孕前和产前 环境可能会影响后代大脑发育，这可能是炎症的最佳特征。 同时使用多种细胞因子，因为它们似乎相互依赖地起作用——经常一起作用的细胞因子 细胞因子网络的使用已成为一种越来越流行的方法。 考虑到特定的细胞因子网络与某些特定的细胞因子网络相关，对炎症进行概念化和分析 此外，特定的细胞因子网络。 怀孕期间的变化与后代神经发育结果的改变有关。 鉴于人们的认识不断增强，这些研究几乎没有在独立数据集中得到重现。 由于神经科学研究的可重复性有限，美国国立卫生研究院 (NIH) 牵头采取了紧急行动， 严格设计的实验和提高的再现性所提出的总体目标。 研究旨在探讨多种孕前和产前因素如何影响母亲的全身系统 怀孕期间的炎症以及后代神经发育的相关改变，同时 满足创新研究设计中更高的严谨性和可重复性的需求，该设计将复制 跨三个高维数据集的复杂多变量分析该特定目标。 建议是： 1) 确定产妇在怀孕期间对产妇炎症环境的社会心理影响因素 2) 确定妊娠期间母体炎症环境的有效健康指标； 3) 确定具有不同孕产妇系统模式的参与者亚组； 炎症并检查健康心理社会因素之间潜在的相关相互作用，以及 该提案旨在创新性地分析与每个簇相关的神经发育结果。 细胞因子网络活动作为孕前和产前各方面的潜在途径 另外，考虑到环境使用多元统计技术改变后代的神经发育。 由于科学的可重复性经常面临挑战，分析结果将在三个方面进行交叉验证 独立的数据集。