Recent evidence indicates that the human fetus is exposed to profound influences that have permanent implications for health. Maternal stress initiates a cascade of events that alter normal developmental processes in the human fetus. Human fetuses exposed to elevated stress signals have impaired learning in utero and are at three-fold increased risk for preterm birth and low birth weight. Moreover, as many as one-half of the infants born early or small, have motor, sensory or cognitive handicaps. The primary aim of this five-year proposal is to determine the influence of prenatal maternal stress and maternal neuroendocrine responses on fetal behavior and to assess the relationship between fetal behavior and infant development in a sample of 200 women (one-half Anglo, one-half Hispanic).
The specific aims are to: (a) Identify the primary stress factors that influence fetal behavior and (b) infant development. Stress will be measured (interviews and questionnaires) five times during pregnancy. Fetal behavior and development will be quantified by conventional measures of fetal growth and by measures of fetal behavioral state, movement (at rest and challenge), reactivity and habituation of fetal heart rate (FHR). Infant behavior will be assessed with the Bayley scales of Development, the Neuromotor Status Examination and by basal and circadian measures of hypothalamic-pituitary-adrenal (HPA) activity: (c) Determine the influence of maternal stress-related (HPA) axis activity and disregulation on fetal and infant behavior and infant HPA activity. Because maternal stress alters peptide receptors and brain peptide levels in the fetal rat brain and because it influences human fetal behavior and birth outcomes, maternal peptide levels will be assayed from blood obtained at each visit. The influence of maternal stress peptides on infant behavior and HPA activity will be determined at six weeks, six, twelve and twenty-four months. (d) Describe the relationship between fetal behavior and infant outcome. A sensitive measure of fetal CNS activity (habituation) will be integrated with contemporary measures of fetal behavior at rest and after challenge, to describe fetal maturation. These measures will be entered into models to predict infant neuromotor development. This project is designed to identify maternal stressful conditions that are harmful to the fetus by examination of the timing and duration of stress, by investigation of biological mechanisms related to prenatal stress, specifically the HPA and placental axis and by longitudinal studies of developmental consequences of prenatal stress in the infant.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS041298-04
Application #
6837627
Study Section
Special Emphasis Panel (ZRG1-BBBP-2 (01))
Program Officer
Hirtz, Deborah G
Project Start
2002-01-23
Project End
2006-12-31
Budget Start
2005-01-01
Budget End
2005-12-31
Support Year
4
Fiscal Year
2005
Total Cost
$607,451
Indirect Cost
Name
University of California Irvine
Department
Psychiatry
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Fox, Molly; Sandman, Curt A; Davis, Elysia Poggi et al. (2018) A longitudinal study of women's depression symptom profiles during and after the postpartum phase. Depress Anxiety 35:292-304
Riley, Jeffrey D; Chen, E Elinor; Winsell, Jessica et al. (2018) Network specialization during adolescence: Hippocampal effective connectivity in boys and girls. Neuroimage 175:402-412
Sandman, Curt A; Curran, Megan M; Davis, Elysia Poggi et al. (2018) Cortical Thinning and Neuropsychiatric Outcomes in Children Exposed to Prenatal Adversity: A Role for Placental CRH? Am J Psychiatry 175:471-479
Glynn, Laura M; Stern, Hal S; Howland, Mariann A et al. (2018) Measuring novel antecedents of mental illness: the Questionnaire of Unpredictability in Childhood. Neuropsychopharmacology :
Howland, Mariann A; Sandman, Curt A; Glynn, Laura M (2017) Developmental origins of the human hypothalamic-pituitary-adrenal axis. Expert Rev Endocrinol Metab 12:321-339
Hahn-Holbrook, Jennifer; Davis, Elysia P; Glynn, Laura M (2017) Response to ""Cortisol in human milk: The good, the bad, or the Ugly?"" Obesity (Silver Spring) 25:1154
Davis, Elysia Poggi; Stout, Stephanie A; Molet, Jenny et al. (2017) Exposure to unpredictable maternal sensory signals influences cognitive development across species. Proc Natl Acad Sci U S A 114:10390-10395
Curran, Megan M; Sandman, Curt A; Poggi Davis, Elysia et al. (2017) Abnormal dendritic maturation of developing cortical neurons exposed to corticotropin releasing hormone (CRH): Insights into effects of prenatal adversity? PLoS One 12:e0180311
Davis, Elysia Poggi; Head, Kevin; Buss, Claudia et al. (2017) Prenatal maternal cortisol concentrations predict neurodevelopment in middle childhood. Psychoneuroendocrinology 75:56-63
Moog, Nora K; Buss, Claudia; Entringer, Sonja et al. (2016) Maternal Exposure to Childhood Trauma Is Associated During Pregnancy With Placental-Fetal Stress Physiology. Biol Psychiatry 79:831-839

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