DESCRIPTION (provided by applicant): Despite considerable evidence documenting the effects of prenatal maternal stress and emotions on birth and early child outcomes, the biological pathways by which maternal stress is transferred to children are not yet well understood. The proposed study will test a set of novel hypotheses about maternal stress and allostatic load (physiological dysregulation across multiple systems due to cumulative wear-and-tear associated with chronic and acute stress exposure) during the preconception and prenatal periods. The study focuses primarily on HPA axis regulatory mechanisms in a sample of 201 diverse mother-child pairs, particularly the prediction of child neurodevelopmental outcomes and stress regulation at ages 2 and 3 and cellular aging (indexed by telomere length) in both young children and their mothers. Our inclusion of the preconception period is innovative and yields a more comprehensive understanding of developmental origins (including fetal programming) of later health and developmental competence. One overall objective is to identify modifiable risk factors that can be targeted for early effective prevention of adverse health, neurocognitive, and behavioral outcomes throughout the lifespan. Participants will be recruited from an enrolled cohort of ethnically diverse, mostly low-income women in Washington, DC and Lake County, IL near Chicago as part of a large multi-site NIH collaborative study (Child Community Health Network Study; CCHN). The parent study includes extensive interview measures of maternal stress in preconception and pregnancy and maternal biomarkers that pose risk for disease in the next generation, creating a unique opportunity to examine prospective predictors of child outcomes. The specific aims are to examine effects of maternal stress and allostatic load, especially HPA regulation during preconception and in pregnancy on outcomes at ages 2 and 3. The outcomes are: (1) children's cortisol responses to acute laboratory stressors and circadian regulation of cortisol production; (2) children's fearful or anxious temperament measured by innovative observational laboratory testing; (3) children's neurocognitive functioning using standardized assessments; (4) children's leukocyte telomere length at age 2 and rates of shortening from ages 2 to 3. We will also examine leukocyte telomere length of mothers as a function of stress and test for mother-child associations. RELEVANCE: This study addresses an NICHD research priority in 2011 to identify developmental origins of susceptibility to later health, disease, and longevity. Results will provide the first evidence about plausible biological pathways prior to pregnancy that, in turn, program prenatal and postnatal development, taking into consideration many other known environmental and biological influences. The findings have the potential to yield new understanding about the pervasive, serious maternal and child health disparities that extend throughout the lifespan and disproportionately impact low income, minority populations.

PUBLIC HEALTH RELEVANCE: Adult diseases with developmental origins including neurocognitive disorders are estimated to take an immense toll on our nation's health. The proposed research will prospectively investigate whether maternal factors in the preconception period and in pregnancy, especially stress and HPA regulatory mechanisms, alter the behavioral, stress regulatory and neurocognitive outcomes of young children, as well as effects on cellular aging processes in mother-child pairs. Findings will provide a new foundation for developing potentially powerful preventive interventions to improve children's lifelong well-being.