Prenatal stress biology, infant body composition and obesity risk

Summary

Principal Investigator: Sonja Entringer
Affiliation: University of California
Country: USA
Abstract: DESCRIPTION (provided by applicant): The goal of our study is to examine the influence of adverse intrauterine conditions, or prenatal stress, on newborn and infant body composition and obesity risk. Obesity is one of the most important health issues facing our nation. The underlying causes at the individual level, and the reasons for its rapid increase in the population are not well-understood. Evidence suggests that the origins of obesity and its sequelae can be traced back to the intra-uterine period of life, at which time exposure to suboptimal conditions during development may result in fetal programming of physiological systems that then confer increased risk for obesity in childhood and adult life. The overwhelming majority of human epidemiological studies of fetal programming of obesity have relied on measures of either size at birth (such as low birth weight or small-for-gestational age birth), or fetal and early postnatal growth velocity, as markers of adverse intrauterine exposures. We propose an innovative and novel application of the fetal programming paradigm by emphasizing the use of a set of stress-related intrauterine maternal-placental-fetal (MPF) biological processes as the principal markers of exposure to intrauterine insult because MPF biological stress parameters may act as "sensors" of the quality of the intrauterine environment as well as "transducers" of its effects on the developing fetus and subsequent childhood and adult obesity risk. The specific questions addressed in our study include the following: (1) Do MPF indices of prenatal stress exposure over human gestation predict newborn body composition and change in body composition from birth until 6 months age, after accounting for the effects of other established risk factors for obesity? (2) Are there sensitive periods during gestation when the developing fetus is particularly vulnerable to the effects of prenatal biological stress on body composition? (3) Are MPF biological stress measures of the intrauterine environment more specific and sensitive predictors of newborn and infant body composition than currently-used measures of birth outcomes or fetal and early postnatal growth? (4) What are the consequences of MPF endocrine/immune-related changes in body composition on metabolic function (insulin sensitivity)? (5) Are the effects of prenatal biological stress on body composition mediated through a change in energy balance homeostasis set points and energy flux over time? We propose to conduct a prospective, longitudinal, follow-up study in a population-based cohort of infants born to mothers who will participate in a NIH-funded study of biological and behavioral processes in pregnancy. We will have extensive characterization in this infant cohort over the course of their intrauterine life and birth with all the prenatal measures required to address the above questions, including serial measures of the maternal-placental- fetal endocrine and immune/inflammatory milieu, serial ultrasound-based measures of fetal biometry, clinical measures of obstetric complications, measures of maternal biophysical, sociodemographic, behavioral, psychosocial characteristics, and measures of the birth phenotype. From this cohort we will recruit a sample of 120-140 children at birth and follow them up until 6 months age. We propose two major study assessments at T1=0-2 weeks and T2=6 months age. At each assessment our primary study outcome, child body composition, will be quantified by dual energy x-ray absorptiometry (DXA);total energy expenditure (TEE) will be quantified using the doubly labeled water (DLW) method;and metabolic function (insulin sensitivity) will be quantified from measures of blood glucose and insulin. Infant nutrition and feeding practices will be assessed concurrently using multiple-pass 24h diet recalls. State-of-the-art statistical modeling techniques for parametric and non-parametric repeated measures, time- series data, including generalized additive models, polynomial distributed lag, classification and regression trees, and multivariate regression analysis will be used to address the study aims. The significance and impact of this study derives from the importance of achieving at a better understanding of the underlying causes for increased susceptibility for obesity, thereby informing the development of new markers for early identification of risk and targets for intervention. PUBLIC HEALTH RELEVANCE: This proposal addresses one of the most important public health issues in our nation - the problem of childhood obesity. Several studies suggest the origins of obesity and its sequelae can be traced back to the intrauterine period of life, at which time exposure to suboptimal conditions during development may result in fetal programming of physiological systems that confer increased risk in that individual for becoming obese in childhood and adult life. Several key questions still remain to be answered about the mechanisms underlying this process. The main goal of our proposed study is to examine the influence of adverse intrauterine conditions, or prenatal stress, on newborn and infant body composition and obesity risk. By using biological (maternal-placental- fetal endocrine and immune) stress measures that are known to reflect a variety of possible intrauterine perturbations, we suggest our approach will be more effective in capturing fetal exposure to a broader set of factors than other studies that have focused primarily on size at birth or maternal under- or overnutrition during pregnancy. By examining changes in infant energy balance over time, our study will clarify whether the mechanisms that underlie the effects of exposure to adverse intrauterine conditions relate to alterations of this particularly important regulatory processes in early life. By concurrently assessing infant insulin sensitivity, we will be able to study the consequences of intrauterine perturbation-related changes in newborn and infant body composition on metabolic function. Thus, the scientific significance of this research is that it will clarify the mechanisms that underlie individual vulnerability for in utero stress-related obesity outcomes. The public health impact is that the information gained from this study will contribute knowledge that is required to ultimately develop and test interventions to prevent, minimize or reverse the risk of a child becoming obese as a consequence of the exposures she or he experienced during intrauterine life, and thereby promote better health for our children and future generations.
Funding Period: ----------------2010 - ---------------2015-
more information: NIH RePORT

Top Publications

  1. pmc Brown adipose tissue quantification in human neonates using water-fat separated MRI
    Jerod M Rasmussen
    Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, California, United States of America
    PLoS ONE 8:e77907. 2013
  2. pmc Maternal positive affect over the course of pregnancy is associated with the length of gestation and reduced risk of preterm delivery
    Annette Voellmin
    University of California, Irvine Development, Health, and Disease Research Program DHDRP, 333 The City Drive West, Suite 1200, Orange, CA, USA Psychiatric Clinics of the University of Basel, Center for Specific Psychotherapy, CBT Unit, Basel, Switzerland
    J Psychosom Res 75:336-40. 2013
  3. pmc Developmental programming of obesity and metabolic dysfunction: role of prenatal stress and stress biology
    Sonja Entringer
    Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA
    Nestle Nutr Inst Workshop Ser 74:107-20. 2013
  4. pmc Stress and telomere biology: a lifespan perspective
    Idan Shalev
    Department of Psychology and Neuroscience, Duke University, Durham, NC, USA Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA Electronic address
    Psychoneuroendocrinology 38:1835-42. 2013
  5. pmc Impact of stress and stress physiology during pregnancy on child metabolic function and obesity risk
    Sonja Entringer
    Department of Pediatrics, University of California, Irvine, California, USA
    Curr Opin Clin Nutr Metab Care 16:320-7. 2013
  6. pmc Maternal psychosocial stress during pregnancy is associated with newborn leukocyte telomere length
    Sonja Entringer
    Department of Pediatrics, University of California, Irvine, School of Medicine, Irvine, CA 92697, USA
    Am J Obstet Gynecol 208:134.e1-7. 2013
  7. pmc Fetal programming of brain development: intrauterine stress and susceptibility to psychopathology
    Claudia Buss
    Department of Pediatrics, University of California, Irvine, School of Medicine, Irvine, CA 92697, USA
    Sci Signal 5:pt7. 2012
  8. pmc Impaired executive function mediates the association between maternal pre-pregnancy body mass index and child ADHD symptoms
    Claudia Buss
    Department of Pediatrics, University of California Irvine, School of Medicine, Irvine, California, United States of America
    PLoS ONE 7:e37758. 2012
  9. pmc The contribution of maternal stress to preterm birth: issues and considerations
    Pathik D Wadhwa
    Departments of Psychiatry and Human Behavior, Obstetrics and Gynecology, and Epidemiology, University of California, Irvine, School of Medicine, 3177 Gillespie Neuroscience Research Facility, Irvine, CA 92697, USA
    Clin Perinatol 38:351-84. 2011
  10. pmc Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood
    Sonja Entringer
    Department of Pediatrics, University of California, Irvine, CA 92697, USA
    Proc Natl Acad Sci U S A 108:E513-8. 2011

Scientific Experts

  • Pathik Wadhwa
  • Sonja Entringer
  • Claudia Buss
  • Elissa S Epel
  • Jue Lin
  • Idan Shalev
  • Annette Voellmin
  • Jerod M Rasmussen
  • James M Swanson
  • Elizabeth H Blackburn
  • Nora Moog
  • Eli Puterman
  • Babak Shahbaba
  • Owen M Wolkowitz
  • Fariba Oveisi
  • Theo G M van Erp
  • Daniele Piomelli
  • Ana Guijarro
  • Annie Nguyen
  • Hyagriv N Simhan
  • Steven G Potkin
  • Elysia Poggi Davis
  • Curt A Sandman
  • Calvin J Hobel
  • Dirk H Hellhammer
  • Stefan Wüst
  • Robert Kumsta

Detail Information

Publications11

  1. pmc Brown adipose tissue quantification in human neonates using water-fat separated MRI
    Jerod M Rasmussen
    Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, California, United States of America
    PLoS ONE 8:e77907. 2013
    ..86, ICCBAT,FF = 0.93). This study demonstrates the reliability of using multi-echo water-fat MRI in human neonates for quantification throughout the torso of BAT depot volume and fat fraction measurements...
  2. pmc Maternal positive affect over the course of pregnancy is associated with the length of gestation and reduced risk of preterm delivery
    Annette Voellmin
    University of California, Irvine Development, Health, and Disease Research Program DHDRP, 333 The City Drive West, Suite 1200, Orange, CA, USA Psychiatric Clinics of the University of Basel, Center for Specific Psychotherapy, CBT Unit, Basel, Switzerland
    J Psychosom Res 75:336-40. 2013
    ....
  3. pmc Developmental programming of obesity and metabolic dysfunction: role of prenatal stress and stress biology
    Sonja Entringer
    Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA
    Nestle Nutr Inst Workshop Ser 74:107-20. 2013
    ..We discuss putative maternal-placental-fetal endocrine and immune/inflammatory candidate processes that may underlie the long-term effects of intrauterine stress...
  4. pmc Stress and telomere biology: a lifespan perspective
    Idan Shalev
    Department of Psychology and Neuroscience, Duke University, Durham, NC, USA Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA Electronic address
    Psychoneuroendocrinology 38:1835-42. 2013
    ....
  5. pmc Impact of stress and stress physiology during pregnancy on child metabolic function and obesity risk
    Sonja Entringer
    Department of Pediatrics, University of California, Irvine, California, USA
    Curr Opin Clin Nutr Metab Care 16:320-7. 2013
    ..To summarize recent conceptual frameworks and empirical findings addressing the role of prenatal stress and stress biology in the context of fetal programming of metabolic function and obesity risk...
  6. pmc Maternal psychosocial stress during pregnancy is associated with newborn leukocyte telomere length
    Sonja Entringer
    Department of Pediatrics, University of California, Irvine, School of Medicine, Irvine, CA 92697, USA
    Am J Obstet Gynecol 208:134.e1-7. 2013
    ..The objective of the present study was to determine how early in life this effect of stress on LTL is apparent by quantifying the association of maternal psychosocial stress during pregnancy with newborn telomere length...
  7. pmc Fetal programming of brain development: intrauterine stress and susceptibility to psychopathology
    Claudia Buss
    Department of Pediatrics, University of California, Irvine, School of Medicine, Irvine, CA 92697, USA
    Sci Signal 5:pt7. 2012
    ..Additionally, we provide empirical evidence from two recently published papers for fetal programming of human brain development. We conclude by suggesting some future directions for expanding this field of research...
  8. pmc Impaired executive function mediates the association between maternal pre-pregnancy body mass index and child ADHD symptoms
    Claudia Buss
    Department of Pediatrics, University of California Irvine, School of Medicine, Irvine, California, United States of America
    PLoS ONE 7:e37758. 2012
    ..The aim of the present study was to test the hypothesis that this association is mediated by alterations in child executive function...
  9. pmc The contribution of maternal stress to preterm birth: issues and considerations
    Pathik D Wadhwa
    Departments of Psychiatry and Human Behavior, Obstetrics and Gynecology, and Epidemiology, University of California, Irvine, School of Medicine, 3177 Gillespie Neuroscience Research Facility, Irvine, CA 92697, USA
    Clin Perinatol 38:351-84. 2011
    ..Issues related to the characterization and assessment of maternal stress and candidate biologic mechanisms are addressed...
  10. pmc Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood
    Sonja Entringer
    Department of Pediatrics, University of California, Irvine, CA 92697, USA
    Proc Natl Acad Sci U S A 108:E513-8. 2011
    ..This observation may help shed light on an important biological pathway underlying the developmental origins of adult health and disease risk...
  11. pmc Prenatal stress and developmental programming of human health and disease risk: concepts and integration of empirical findings
    Sonja Entringer
    Department of Psychiatry and Human Behavior, University of California, Irvine, School of Medicine, Irvine, California, USA
    Curr Opin Endocrinol Diabetes Obes 17:507-16. 2010
    ....