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

项目摘要 尽管美国的医疗保健服务的可及性和质量有所改善， 社会经济上处于不利地位的家庭和/或少数民族有较高的认知功能受损的风险， 和社会情感的发展。事实上，贫困儿童的发展风险要高出40%。 与非贫困儿童相关的延迟。贫穷使人们不成比例地面临逆境， 父母/儿童的心理社会压力因素（如遭受暴力、经常搬迁）和心理压力因素 导致儿童发育受损的痛苦（如母亲抑郁症）。然而，负 在存在保护性因素的情况下，可以减轻影响。虽然衡量产妇逆境和 保护性因素已被评估与儿童发展，这些因素的综合影响， 对立的力量和表观遗传编程的潜在相关和关键作用尚未确定。 特别是在生命过程的敏感时期，其影响最大。我们 初步数据表明，在两个敏感时期（产前和生命早期）， 表观遗传学程序婴儿反应系统，从而改变儿童的发展。我们的总体假设是 母亲的逆境和保护因素（即，母亲的心理社会经验）面对整个生活- 通过DNA甲基化导致后代认知和社会情感发育差异 （DNAm）的基因在多种生物途径。这项研究结合了回顾性评估和前瞻性评估。 在5次研究访视中采集了375对母婴配对的数据，时间跨度为妊娠至18个月 产后的该建议的具体目标是：1）确定生命过程中孕产妇 心理社会经验和婴儿DNAm的变化在生命的第一年，一个敏感的发展 窗口，2）描述婴儿第一次出生时产后母亲心理社会经验之间的关联 3）确定在两个时间点（1个月和1个月）的DNAm的影响， 12个月）的婴儿发育的前18个月。这项研究将在一个大的， 区域家访计划，使我们能够通过精准的家访和 旨在减少早期发育健康差距的其他战略。

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.