11/15/18. Bowers. Resub R01. Linking pre- and post-natal psychosocial determinants, DNA methylation, and early developmental health disparities

2018 年 11 月 15 日。

• 批准号: 10339401
• 负责人: Katherine A Bowers
• 金额: $ 61.73万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-26 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10339401
• 关键词: Academic achievement; Adolescence; Adverse event; Affect; Arousal; Attention; Behavioral; Biological; Birth; Brain; Child; Child Development; Child Rearing; Childhood; Cognitive; DNA Methylation; Data; Data Collection; Development; Developmental Delay Disorders; Early Intervention; Effectiveness; Emotional; Enrollment; Environment; Epigenetic Process; Evidence based intervention; Exposure to; Family; Fibrinogen; Financial Hardship; Genes; Glucocorticoid Receptor; Goals; Home visitation; Hydroxysteroid Dehydrogenases; Impaired cognition; Impairment; Infant; Infant Development; Intervention; Life; Life Cycle Stages; Link; Measures; Mediating; Minority; Mothers; NR3C1 gene; Outcome; Pathway interactions; Perinatal; Phenotype; Population; Population Heterogeneity; Populations at Risk; Positioning Attribute; Poverty; Predisposition; Pregnancy; Public Health; Race; Reduce health disparities; Research; Risk; Risk Factors; Role; Services; Site; Social support; Stress; System; Time; Translating; United States; Urban Population; Visit; Woman; Work; age related; biological adaptation to stress; dosage; early childhood; epigenetic marker; experience; health care quality; health disparity; improved; in utero; infancy; intervention program; lower income families; maternal depression; maternal risk; novel; novel strategies; offspring; participant enrollment; postnatal; prenatal; prevent; programs; prospective; protective factors; psychological distress; psychosocial; psychosocial stressors; public health relevance; resilience; response; serotonin transporter; social; socioeconomic disadvantage; violence exposure

PROJECT SUMMARY Despite improvements in access and quality of health care in the United States (US), children from socioeconomically disadvantaged families and / or of minority race have an elevated risk for impaired cognitive and social-emotional development. Indeed, children in poverty are 40% more likely to experience developmental delays relative to children not in poverty. Poverty engenders disproportionate exposure to adversity including parental/child psychosocial stressors (such as, exposure to violence, frequent relocation) and psychological distress (such as, maternal depression) that contribute to impaired childhood development. However, negative effects may be mitigated in the presence of protective factors. While measures of maternal adversity and protective factors have been evaluated in association with child development, the combined effects of these opposing forces and the potentially related and critical role of epigenetic programming have not been determined. In particular, at sensitive periods across the life-course when their effects have the strongest impact. Our preliminary data suggest that maternal adversity during two sensitive time periods (prenatally and early life) epigenetically program infant response systems, thereby altering child development. Our overall hypothesis is that maternal adversity and protective factors (i.e., maternal psychosocial experience) faced across the life- course contribute to offspring cognitive and social-emotional developmental disparities through DNA methylation (DNAm) of genes in multiple biologic pathways. This study combines retrospective assessment and prospective data collection on 375 mother-infant dyads captured in 5 study visits spanning pregnancy through 18 months postnatal. The specific aims of the proposal are 1) determine the association between the life-course maternal psychosocial experience and the change in infant DNAm during the first year of life, a sensitive developmental window, 2) characterize the association between postnatal maternal psychosocial experiences in the infant’s first year of life and infant DNAm at one year, and 3) determine the impact of DNAm at two time points (1 month and 12 months) of infant development across the first 18 months. This research will be conducted within a large, regional home visiting program, uniquely positioning us to translate findings through precision home visiting and additional strategies aimed at reducing early developmental health disparities.

项目概要 尽管美国医疗保健的可及性和质量有所改善，但来自美国的儿童 社会经济弱势家庭和/或少数族裔的认知障碍风险较高 和社会情感发展。事实上，贫困儿童经历发育障碍的可能性高出 40% 与非贫困儿童相关的延误。贫困导致人们过度遭受逆境，包括 父母/儿童心理社会压力（例如，遭受暴力、频繁搬迁）和心理压力 导致儿童发育受损的痛苦（例如母亲抑郁）。然而，负面 在存在保护因素的情况下，影响可能会减轻。虽然孕产妇逆境的措施和 已对与儿童发育相关的保护因素进行了评估，这些因素的综合影响 反对力量以及表观遗传编程的潜在相关和关键作用尚未确定。 特别是在生命历程的敏感时期，其影响最为强烈。我们的 初步数据表明，母亲在两个敏感时期（产前和生命早期）的逆境 表观遗传编程婴儿反应系统，从而改变儿童发育。我们的总体假设是 母亲一生中面临的逆境和保护因素（即母亲的社会心理经历） 通过DNA甲基化当然会导致后代认知和社会情感发展差异 (DNAm) 多种生物途径中的基因。本研究结合了回顾性评估和前瞻性评估 在怀孕至 18 个月的 5 次研究访问中收集了 375 名母婴二人组的数据 产后。该提案的具体目标是 1) 确定生命全程孕产妇之间的关联 心理社会经历和婴儿第一年 DNAm 的变化是一个敏感的发育过程 窗口，2）描述婴儿出生后产后母亲心理社会经历之间的关联 生命年份和婴儿一年时的 DNAm，以及 3) 确定 DNAm 在两个时间点（1 个月和 1 个月）的影响 12 个月）的婴儿在前 18 个月的发育。这项研究将在一个大范围内进行， 区域家访计划，使我们能够通过精确的家访和 旨在减少早期发育健康差异的其他战略。