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).