Adverse birth outcomes (reduced length of gestation/ impaired fetal growth) are recognized as the most significant problem in maternal-child health in the United States. A substantial body of empirical evidence in animals and humans suggests that high levels of maternal psychosocial stress in pregnancy constitute an independent risk factor for these adverse outcomes. However, the translation of this knowledge from the population to individual level for risk assessment and intervention is limited by the fact that the commonly-used self-report, retrospective recall measures of stress have low sensitivity and specificity in predicting adverse birth outcomes. Two major weaknesses of the stress and birth outcome literature relate to (a) limitations in the traditional approach to assess maternal psychosocial stress, and (b) the failure to assess and account for individual differences in biological stress responsivity. Recent advances in ecological momentary assessment (EMA) sampling methods now afford the opportunity of assessing the dynamic interplay of psychological, behavioral and biological processes in natural settings to address shortcomings and knowledge gaps in this literature. We propose to import and adapt these methods into the area of behavioral perinatology research.
Our specific aims are: 1) To estimate the magnitude of the effect of maternal psychosocial stress on a) maternal-placental-fetal (MPF) hormonal parameters, and b) birth outcomes;2) To estimate the magnitude of the effect of maternal biological stress reactivity on a) MPF hormonal parameters, and b) birth outcomes;and 3) To determine whether the magnitude of the effect of maternal stress is modulated by the stage in gestation of occurrence of stress. Complete prospective data will be collected in a sample of at least 120 pregnant women over three 4-day assessments in early, mid and late gestation. Electronic diaries (PDAs) will be used to collect 15 measures/day of subjects'psychological state and other contextual information. Continuous ambulatory measures of maternal heart rate, respiration and physical activity, as well as seven saliva samples over the course of each day, will be collected for indicators of autonomic and endocrine activity. At the end of each ambulatory session, a maternal blood sample will be collected for measures of MPF endocrine mediators (CRH, E3). These data will be merged in time-synchronized datasets;time-invariant and time-variant variables will be computed by methods including subject-specific auto-regression models, and multivariate and longitudinal regression analysis will be employed to test the specific aims and hypotheses using generalizing estimating equations (GEE) and multi-level mixed models with fixed and random effects (hierarchical linear models;HLM). The scientific significance of our proposal pertains to understanding psychobiological mechanisms that are likely determinants of individual vulnerability for stress-related adverse birth outcomes, whereas the public health significance of this research pertains to the development and assessment of new measures and methodologies that will increase the specificity and sensitivity of biopsychosocial risk assessment and provide an empirical basis for the development and evaluation of comprehensive intervention strategies to reduce the unacceptably high incidence of adverse birth outcomes. Findings from our study also will inform the proposed psychobiological stress assessment protocol of the National Children's Study (NCS).

Public Health Relevance

This proposal addresses what is arguably the most important public health issue in maternal-child health in our nation - adverse pregnancy and birth outcomes related to shortened gestation/preterm birth and reduced fetal growth/low birth weight. Several lines of animal and human evidence converge to convincingly suggest that maternal psychosocial stress-related processes in pregnancy represent an important and potentially modifiable risk factor for adverse birth outcomes and subsequent child and adult health outcomes. However, despite many years of empirical research and findings, key questions still remain to be answered about the nature, mechanism and timing of effects of prenatal stress. We argue that the critical first step towards translating prenatal stress findings from the population to the individual level is to develop ways to identify which subgroup(s) of pregnant women (under what circumstances/ context, and at which time/stage in gestation) are particularly susceptible to the detrimental effects of prenatal stress. We propose that newer, innovative technologies and methods based on real-time, ambulatory, repeated sampling of psychological, behavioral and biological states (i.e., ecological momentary assessment (EMA)) can be adapted successfully to achieve this objective. The scientific significance of this research is that it will clarify psychobiological mechanisms that are likely determinants of individual vulnerability for stress-related adverse birth outcomes. The public health impact is that it will increase the sensitivity and specificity of biopsychosocial risk assessment and provide an empirical basis for the development and evaluation of comprehensive intervention strategies to prevent or manage stress in pregnancy and reduce its adverse health consequences in the mother and her unborn child. The objectives, approach, and outcomes of our proposed research are consistent with the emphasis placed by the NIH on clinical translational research and the aspiration in Systems Biology to progress towards the new P4 medicine (predictive, preventive, personalized, participatory) of the future.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD060628-05
Application #
8610933
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Reddy, Uma M
Project Start
2010-02-01
Project End
2015-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
5
Fiscal Year
2014
Total Cost
$788,387
Indirect Cost
$274,694
Name
University of California Irvine
Department
Psychiatry
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
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Entringer, Sonja; Wadhwa, Pathik D (2013) Developmental programming of obesity and metabolic dysfunction: role of prenatal stress and stress biology. Nestle Nutr Inst Workshop Ser 74:107-20
Entringer, Sonja (2013) Impact of stress and stress physiology during pregnancy on child metabolic function and obesity risk. Curr Opin Clin Nutr Metab Care 16:320-7
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Wadhwa, Pathik D; Entringer, Sonja; Buss, Claudia et al. (2011) The contribution of maternal stress to preterm birth: issues and considerations. Clin Perinatol 38:351-84
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