Early Life Adversity and Adulthood Health: The Role of Pubertal Development

项目概要： 心血管疾病（CVD）和癌症仍然是美国妇女死亡的主要原因， 占每年死亡人数的近一半。最近由NHLBI和NCI领导的专家小组研讨会 强调了早期生活事件/暴露在塑造CVD/癌症结局风险轨迹方面的重要性 以及需要进行更多的研究，以确定具体的环境和个人层面的脆弱性因素， 早期生活事件/暴露传递这种风险的机制。目前，现有的研究局限于 固有的方法挑战（例如，事件/暴露和结果之间的长潜伏期 兴趣），以及相关的发展和流行病学文献整合不良。解决这些 局限性，目前的研究建议利用具有里程碑意义的NICHD研究早期儿童保育和青年 发展（SECCYD; 1991-2006），一项对儿童从出生到15.5岁进行随访的大规模前瞻性研究， 评估一个生命过程模型，其中假设早期生命经历会导致中期死亡的风险。 与心血管疾病/癌症风险相关的健康结果，部分通过时间和克里思的相关变化， 青春期成熟在所提出的模型中强调青春期成熟是一种潜在的机制， 早期生活经历到成年期的健康/疾病风险基于丰富的（尽管在很大程度上独立） 文献显示：1）早期生活逆境预示着青春期成熟的速度更早和更快，2） 青春期成熟可预测青春期和成年期的CVD风险因素以及CVD/癌症事件， CVD/癌症特异性死亡率和全因死亡率。目前的研究正在寻求NIH的资金支持， 在NICHD SECCYD的女性参与者中（n=387，估计473的80%返回;年龄25-30岁， 研究期间）完成一次随访研究访问，评估年轻人的健康/疾病风险参数 成年单次随访访视将需要对心脏代谢健康和 炎症可以预测疾病的长期风险。评估将来自身体检查， 检查、抽血和综合病史/健康行为评估。的措施 从目前的研究中产生的，将与现有的最先进的早期评估进行审查， 生活环境和青春期发育作为原始NICHD SECCYD数据收集的一部分进行。 具体而言，青春期前的环境将以儿童社会经济地位的衡量标准为特征， 婴儿-母亲依恋、母亲敏感、父亲缺席、负面生活事件和虐待儿童。青春期 发育将使用来自年度体检的青春期时间和克里思的测量来表征。 由受过训练的医疗提供者使用标准方法进行的检查，以确定性成熟的阶段。 所提出的模型，如果得到肯定，将指出新的干预机会，以减少心血管疾病/癌症的风险， 成年期的目标，例如，推迟青春期的开始（例如，通过减少早期生活中的逆境） 或减轻青春期提前对健康的影响（例如，通过改善相关健康状况的管理）。

PROJECT SUMMARY: Cardiovascular disease (CVD) and cancer remain the leading causes of mortality in American women, accounting for nearly half of all deaths annually. Recent NHLBI and NCI-led Expert Panel Workshops have highlighted the significance of early life events/exposures in shaping trajectories of risk for CVD/cancer outcomes and the need for additional research to identify specific environment- and person-level vulnerability factors and mechanisms by which early life events/exposures transmit such risk. At present, existing studies are limited by inherent methodological challenges (e.g., long latency periods between the event/exposure and outcomes of interest) as well as by poor integration of relevant developmental and epidemiologic literatures. To address these limitations, the current study proposes to leverage the landmark NICHD Study of Early Child Care and Youth Development (SECCYD; 1991-2006), a large-scale, prospective study of children followed from birth to age 15.5, to evaluate a life course model whereby early life experiences are hypothesized to confer risk for intermediate health outcomes relevant to CVD/cancer risk, partially through correlated variation in the timing and tempo of pubertal maturation. Pubertal maturation is emphasized in the proposed model as a potential mechanism linking early life experiences to adulthood health/disease risk based on abundant (though as yet largely independent) literatures showing 1) early life adversity predicts earlier and faster rates of pubertal maturation and 2) earlier pubertal maturation predicts CVD risk factors in adolescence and adulthood as well as incident CVD/cancer, CVD/cancer-specific mortality, and all-cause mortality. The current study seeks NIH funding to support the return of the female participants in the NICHD SECCYD (n=387, estimating 80% return of 473; ages 25-30 over the study period) to complete a single follow-up study visit assessing parameters of health/disease risk in young adulthood. The single follow-up visit will entail detailed assessments in domains of cardio-metabolic health and inflammation known to predict long-term risk for disease. Assessments will be derived from a physical examination, blood draw, and comprehensive medical history/health behavior evaluation. The measures generated from the current study will be examined in relation to existing state-of-the-art assessments of early life environments and pubertal development performed as a part of the original NICHD SECCYD data collection. Specifically, the pre-pubertal environment will be characterized by measures of childhood socioeconomic status, infant-mother attachment, maternal sensitivity, father absence, negative life events, and child abuse. Pubertal development will be characterized using measures of pubertal timing and tempo derived from annual physical exams performed by trained medical providers using standard methods to determine stages of sexual maturity. The proposed model, if affirmed, will point to novel opportunities for intervention to lessen CVD/cancer risk in adulthood by targeting at-risk girls to, for example, delay pubertal onset (e.g., via reductions in early life adversity) or to mitigate effects of earlier puberty on health (e.g., via improved management of relevant health conditions).