Pathik D. Wadhwa, M.D., Ph.D.
Professor of Psychiatry & Human Behavior, Obstetrics & Gynecology, Pediatrics, and Epidemiology
Director, UC Irvine Development, Health and Disease Research Program
|fetal/developmental programming of health and disease risk, behavioral medicine, stress, pregnancy, fetal development, prematurity, neuroendocrine, immune, genetic, epigenetic, telomere biology, maternal-child health, reproductive epidemiology|
|URLs||Department of Psychiatry & Human Behavior|
|UC Irvine Genetic Epidemiology Research Institute|
Academy of Behavioral Medicine Research – Neal E. Miller New Investigator Award for early career contributions to behavioral medicine (1997).
Perinatal Research Society – Young Investigator Award (1998).
First Independent Research Support and Transition (FIRST) Award, NIH/National Institute of Child Health and Human Development (1998-2003).
Consultant, NIH/National Institute of Child Health and Human Development--Perinatology Research Branch (1998).
Member, Advisory Committee, The National Children’s Study (NIH, CDC, EPA) (Perinatal Assessment Group) (2003).
Member, Advisory Committee, Centers for Disease Control and Prevention (CDC) Reproductive Health Branch (Developing a Research Agenda on Prevention of Premature Birth) (2004).
Member, Scientific Advisory Board, Swiss Etiological Study of Adjustment and Mental Health (SESAM), Basel, Switzerland (2005-07).
Executive Committee, National Children's Study, Orange County, California, Vanguard Center (2005-present).
Member, Steering Committee, The U.S. National Children’s Study (2006-08).
Excellence in Mentoring Award, UC Irvine Institute for Clinical and Translational Science (2012).
Visiting Professor, NIH/ National Institute of Child Health and Human Development Perinatology Research Branch, Detroit, MI (May 2012).
Developmental robustness, or how well an individual is built, has an important implication for her or his subsequent state of health and risk of developing disease(s) over the lifespan. Development is a plastic process, wherein a range of different structural and functional phenotypes can emerge from any given genotype as a function of the nature of environmental conditions during embryonic, fetal and early postnatal life. The UC Irvine Development, Health and Disease Research Program is a trans-disciplinary, translational effort to elucidate the nature and consequences of the interplay between biological, behavioral, social and environmental conditions during early human development (intrauterine and early postnatal life) on subsequent health outcomes over the lifespan, and on the propensity, or susceptibility, for developing one or more of the complex common disorders that collectively confer the major global burden of disease. Our approach, broadly informed and guided by an evolutionary-developmental perspective, seeks to address developmental processes underlying the transduction of signaling of short- and long-term energetic state-related parameters in the maternal environment (e.g., nutrition, stress) on outcomes related to fetal growth and maturation, birth phenotypes, and newborn, infant and child physical and mental health. Our studies also focus on putative mechanisms involving maternal-placental-fetal endocrine, immune, vascular and genetic/epigenetic processes, including telomere and mitochondrial biology.
Established in 2000 with set up and infrastructure provided by the University, our program had been supported continuously since its inception by several major research grants from the National Institutes of Health (NIH) and other agencies. Our interdisciplinary team currently includes a total of 25 faculty investigators directly funded by our program (of which 13 are based at UC Irvine and 12 at other institutions), along with several additional collaborators. We have been conducting primarily prospective, longitudinal studies of human pregnancy and birth outcomes, with an initial focus on the effects of maternal-fetal stress and stress-related biological processes on prematurity-related birth outcomes. Our studies have more recently expanded to include follow-up investigations of the longer-term effects of various prenatal stress and nutrition-related exposures on newborn, infant and child health outcomes, with an emphasis on newborn and infant phenotypes related to a) obesity, energy balance homeostasis, and metabolic function, and b) structural and functional brain development. Our on-going studies in population-based samples from diverse socioeconomic and racial/ethnic backgrounds utilize state-of-the-art ecological momentary assessment (EMA) approaches to characterize maternal states (psychosocial stress, social interactions), behaviors (diet, physical activity, sleep) and physiology (autonomic, endocrine and immune function) in real time and natural settings over the course of pregnancy. Assessments of newborn and infant outcomes related to body composition/ adiposity, metabolic function and energy expenditure in free-living conditions are performed serially across infancy using dual-emission x-ray absorptiometry imaging (DXA), measurement of glucose-insulin homeostasis, and quantification of traceable hydrogen (deuterium) and oxygen (18O) decay using doubly-labeled water (DLW), respectively. Characterizations of newborn and infant brain structure, connectivity and function are also performed serially across infancy using magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), resting state fMRI, and laboratory- and home-based neurocognitive, affective and behavioral assessment protocols, respectively. Study hypotheses address i) the role of maternal-placental-fetal endocrine, immune/ inflammatory and oxidative state-related processes across gestation as key mediators of fetal programming of birth, newborn and infant health outcomes, ii) the role of maternal–fetal gene–environment interactions, with a focus on genes and gene networks (including mitochondrial genetic variation) implicated in the regulation of key enzyme systems, steroid hormones and peptides associated with stress as well as fetal development, and iii) the biological, behavioral and social determinants of the well-documented racial/ethnic disparities and the Hispanic acculturation paradox in reproductive and maternal-child health outcomes in the United States. In addition to our UCI-based studies, our program has established formal, funded collaborations with several other investigators and DOHaD-related projects in the U.S., Canada, Europe, Australia and India. Our program also is currently plays a major role in development of stress-related measures and protocols for the U.S. National Children’s Study, one of the largest and most comprehensive proposed studies of the genetic and environ-mental determinants of child development and health.
We welcome collaborations with investigators, postdoctoral researchers and students on projects based at UC Irvine or elsewhere. To sustain and further grow the scope of our research activities we are in the process of recruiting new faculty and postdoctoral research fellows with a strong interest, background, expertise and track record in the area of the fetal/developmental origins of health and disease risk. We seek investigators from diverse backgrounds, including the medical, biological, behavioral or social sciences, whose areas of expertise supplement or complement those described above. We expect to continue our current follow-up studies of newborns and infants into childhood and adolescence, and to supplement our current protocols with additional measures, including but not limited to quantification of maternal breast milk and newborn and infant brown and white adipose tissue and gut microbiome. We also are committed to the development and establishment of protocols to expand our repertoire of newborn, infant and child phenotypes of interest, to include studies of the role of biobehavioral processes in the fetal/developmental programming of the human placenta (e.g., trophoblasts) and stem cells (e.g., hematopoetic, mesenchymal and neural lineages), and of the cardiovascular (e.g., endothelial function and blood pressure regulation), endocrine (e.g., growth, thyroid and reproductive hormones), immune (e.g., innate and adaptive immune responses), pulmonary (e.g., bronchial responsivity and lung function), reproductive (e.g., adrenarche, menarche) and aging-related (e.g., telomere biology) systems. We are interested in comparing and contrasting the effects on human fetal/developmental programming of maternal exposures over her life course, and particularly those during her own early life period, from those during the period of gestation. For new faculty we have the flexibility of offering primary academic appointments in one or more of several departments and programs, including Psychiatry & Human Behavior, Obstetrics & Gynecology, Pediatrics, Medicine, Epidemiology, and Public Health.
SELECTED REPRESENTATIVE PUBLICATIONS
Entringer S, Wadhwa PD. Developmental programming of obesity and metabolic dysfunction: role of prenatal stress and stress biology. Nestle Nutritional Institute Workshop Series (in press).
Shalev I, Entringer S, Wadhwa PD, Wolkowitz OM, Puterman E, Epel ES. Stress and telomere biology: a lifespan perspective. Psychoneuroendocrinology (in press).
Entringer S, Epel ES, Lin J, Buss C, Blackburn EH, Simhan HN, & Wadhwa PD. Maternal psychosocial stress during pregnancy is associated with newborn leukocyte telomere length. American Journal of Obstetrics & Gynecology, 2012 Nov 27. doi:pii: S0002-9378.
Entringer S, Buss C, & Wadhwa PD. Prenatal stress, telomere biology and fetal programming of health and disease risk: Science Signaling, 2012, Oct 30;5(248):pt12.
Buss C, Entringer S, & Wadhwa PD. Fetal programming of brain development - role of intrauterine stress and stress biology in susceptibility for psychopathology. Science Signaling, 2012; Oct 9;5(245):pt7.
Wadhwa PD, Simhan HN, Entringer S, Buss C, Smith R, Hobel CH, Farhana N, Shimmin L, Hixson JE, & Sing CF. Variation in the maternal Corticotrophin Releasing Hormone-Binding Protein (CRH-BP) gene and birth weight in Blacks, Hispanics and Whites. PLoS One, 2012; 7(9):e43931.
Buss C, Entringer S, Swanson JM, & Wadhwa PD. The Role of Stress in Brain Development: The Gestational Environment’s Long-Term Effects on the Brain. Cerebrum April 2012.
Buss C, Entringer S, Davis EP, Hobel CJ, Swanson JM, Wadhwa PD, & Sandman CA. Impaired Executive Function Mediates the Association between Pre-pregnancy BMI and Attention Deficit in the Offspring. PLoS One, 2012; 7(6):e37758.
Entringer S, Buss C, Swanson JM, Cooper DM, Wing DA, Waffarn F, & Wadhwa PD. Fetal Programming of Body Composition, Obesity and Metabolic Function: the Role of Intrauterine Stress and Stress Biology. Journal of Nutrition and Metabolism, 2012; 2012:632548.
Wadhwa PD, Entringer S, Buss C, & Lu MC. The Contribution of Maternal Stress to Preterm Birth: Issues and Considerations. Clinics in Perinatology, 2011; 38(3):351-84.
Entringer S, Epel ES, Kumsta R, Lin J, Hellhammer DH, Blackburn EF, Wüst S, & Wadhwa PD. Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood. Proceedings of the National Academy of Sciences USA, 2011, 108(33):e513-8.
Entringer S, Buss C, Andersen J, Chicz-DeMet A, & Wadhwa PD. Ecological momentary assessment of maternal cortisol profiles over a multiple-day period predicts the length of human gestation. Psychosomatic Medicine, 2011, 73(6):469-474.
Cammack AL, Buss C, Entringer S, Hogue CJ, Hobel CJ, & Wadhwa PD. The association between early life adversity and bacterial vaginosis during pregnancy. American Journal of Obstetrics & Gynecology, 2011, 204(5):431.e1-8.
Denney JM, Nelson EL, Wadhwa PD, Waters TP, Mathew L, Chung EK, Goldenberg RL, & Culhane JF. Longitudinal modulation of immune system cytokine profile during pregnancy. Cytokine, 2011, 53(2):170-177.
Entringer S, Buss C, & Wadhwa PD. Prenatal stress and developmental programming of human health and disease risk: concepts and integration of empirical findings. Current Opinion in Endocrinology, Diabetes and Obesity. 2010, 17(6): 507-516.
Entringer S, Buss C, Shirtcliff EA, Yim IS, Cammack AL, Chicz-DeMet A, Sandman CA, & Wadhwa PD. Attenuation of maternal psychophysiological stress responses over the course of human pregnancy. Stress, 2010, 13(3): 258-268.
Buss C, Entringer S, Cammack AL, Jonazary FR, Chicz-DeMet A, Sandman CA, & Wadhwa PD. The maternal cortisol awakening response (CAR) in human pregnancy is associated with the length of gestation. American Journal of Obstetrics and Gynecology, 2009, 201(4):398.e1-8.
Wadhwa PD, Buss C, Entringer S, & Swanson J. Developmental origins of health and disease: brief history of the approach and current focus on epigenetic mechanisms. Seminars in Reproductive Medicine, 2009, 27:358-368.
Swanson JM, Entringer S, Buss C & Wadhwa PD. Developmental Origins of Health and Disease: Environmental Exposures. Seminars in Reproductive Medicine, 2009, 27:391-402.
Entringer S, Buss C, Kumsta R, Hellhammer DH, Wadhwa PD, Wüst, S. Prenatal psychosocial stress is associated with subsequent working memory performance in young women. Behavioral Neuroscience, 2009, 123(4):886-893.
Entringer S, Kumsta R, Hellhammer DH, Wadhwa PD, Wüst S. Prenatal exposure to maternal psychosocial stress and HPA axis regulation in young adults. Hormones and Behavior, 2009, 55(2):292-298.
Swanson JM & Wadhwa PD. Developmental origins of child mental health disorders. The Journal of Child Psychology and Psychiatry, 2008, 49(10):1009-1019.
Entringer S, Kumsta R, Nelson EL, Hellhammer DH, Wadhwa PD, & Wüst S. Influence of prenatal psychosocial stress exposure on immune function in adult women. Developmental Psychobiology, 2008, 50(6):579-587.
Entringer S, Wüst S, Kumsta R, Layes IM, Nelson EL, Hellhammer DH, & Wadhwa PD. Prenatal psychosocial stress exposure is associated with insulin resistance in young adults. American Journal of Obstetrics and Gynecology, 2008, 199(5), 498.e1-7.
Shimmin L, Natarajan S, Ibarguen H, Montasser M, Kim D-K, Hanis CL, Boerwinkle E, Wadhwa PD, & Hixson JE. CRH gene variation: comprehensive variant and molecular haplotype discovery for disease association and evolutionary studies. DNA Sequence, 2007, 18(6):434-444.
Swanson JM, Kinsbourne M, Nigg J, Lanphear B, Stefanatos GA, Volkow N, Taylor E, Casey BJ, Xavier Castellanos F, & Wadhwa PD. Etiologic subtypes of attention-deficit/hyperactivity disorder: brain imaging, molecular genetic and environmental factors and the dopamine hypothesis. Neuropsychol Rev, 2007, 17: 39-59.
Landrigan PJ, Trasande L, Thorpe LE, Gwynn C, Lioy PJ, D'Alton ME, Lipkind HS, Swanson JM, Wadhwa PD, Clark EB, Rauh VA, Perera FP, & Susser E. The National Children's Study: a 21-year prospective study of 100,000 American children. Pediatrics, 2006, 118(5): 2173-2186.
DuPont NC, Wang K, Wadhwa PD, Culhane JF, & Nelson E. Validation and comparison of Luminex multiplex analysis kits with ELISA: determinations of a panel of 9 cytokines in clinical sample culture supernatants. Journal of Reproductive Immunology, 2005, 66(2):175-191.
Wadhwa PD. Psychoneuroendocrine processes in human pregnancy influence fetal development and health. Psychoneuroendocrinology, 2005, 30:724-743.
Wadhwa PD, Garite TJ, Porto M, Chicz-DeMet A, Dunkel-Schetter C, & Sandman CA. Corticotrophin-releasing hormone (CRH), preterm birth and fetal growth restriction: a prospective investigation. American Journal of Obstetrics and Gynecology, 2004, 191:1063-1069.
Culhane J, Rauh V, Farley-McCollum K, Hogan V, Agnew K, & Wadhwa PD. Maternal stress is associated with bacterial vaginosis in human pregnancy. Maternal and Child Health Journal, 2001, 5(2):127-134.
Wadhwa PD, Culhane J, Rauh V, & Barve SS. Stress and preterm birth: neuroendocrine, immune-inflammatory and vascular mechanisms. Maternal and Child Health Journal, 2001, 5(2):119-125.
Wadhwa PD, Culhane J, Rauh V, Barve SS, Sandman CA, Hobel CJ, Dunkel-Schetter C, & Garite TJ. Stress, infection and preterm birth: a biobehavioral perspective. Pediatric and Perinatal Epidemiology, 2001, 15(2):17-29.
Wadhwa PD, Porto M, Garite TJ, Chicz-DeMet A, & Sandman CA. Maternal CRH levels in the early third trimester predict length of gestation in human pregnancy. American Journal of Obstetrics and Gynecology, 1998, 179:1079-1085.
Wadhwa PD, Sandman CA, Chicz-DeMet A, & Porto M. Placental CRH modulates maternal pituitary-adrenal function in human pregnancy. Annals of the New York Academy of Sciences, 1997; 814:276-281.
Wadhwa PD, Dunkel-Schetter C, Chicz-DeMet A, Porto M, & Sandman CA. Prenatal psychosocial factors and the neuroendocrine axis in human pregnancy. Psychosomatic Medicine, 1996; 58(5): 432-446.
Wadhwa PD, Sandman CA, Porto M, Dunkel-Schetter C, & Garite TJ. The association between prenatal stress and infant birthweight and gestational age at birth: A prospective investigation. American Journal of Obstetrics and Gynecology, 1993; 169: 858-65.
|Grants||Scientific Director, Maternal Stress and Stress Biology in Human Pregnancy - Development of an Optimized Measurement Protocol. A Multi-Site National Children’s Study (NCS) Formative Research Project. Study Locations: Northwestern U; U Pittsburgh/Magee Women’s Hospital; U Pennsylvania/ Children’s Hospital of Philadelphia; U Texas Health Science Center, San Antonio; UC Irvine, NIH/ National Institute of Child Health and Human Development (HHSN-275200503415C); $3,885,600 direct costs, 04/2013 – 03/2016.|
|Principal Investigator, Ecological Momentary Assessment (EMA) of Biobehavioral Processes in Human Pregnancy. NIH/National Institute of Child Health and Human Development (RO1 HD-060628); $2,364,828 direct costs; 02/2010 - 01/2015.|
|Principal Investigator (with Claudia Buss), Fetal Programming of the Newborn and Infant Human Brain. NIH/ National Institute of Mental Health (R01 MH-091351); $2,402,334 direct costs; 12/2010-11/2015.|
|Co-Principal Investigator, Prenatal Stress Biology, Infant Body Composition and Obesity Risk (Sonja Entringer, PI). NIH/ National Institute of Child Health and Human Development (R01 HD-065825); $1,965,485 direct costs; 07/2010 – 06/2015.|
|Principal Investigator (with Claudia Buss), Fetal Programming of Brain Functional Connectivity in Neonates and Infants, NIH/ National Institute of Mental Health (R01 MH-091351 S), $322,324 direct costs, 12/2012 – 11/2015.|
|Principal Investigator (with Sonja Entringer), Fetal Programming of Newborn and Infant Telomere Biology. NIH/National Institute of Child Health and Human Development (Type 3 RO1 HD 060628), $498,892 direct costs, 04/13 - 01/2015 (award expected 04/2012).|
|Co-Principal Investigator, Brown adipose tissue and its metabolic correlates in human newborns and infants (Sonja Entringer and Claudia Buss, PIs), NIH/ National Institute of Diabetes and Digestive and Kidney Diseases (R21 DK-098765), $245,106 direct costs, 04/2013 - 03/2015.|
|Principal Investigator/Program Director, Gene-Environment Interactions in Human Parturition. NIH/National Institute of Child Health and Human Development Program Project Grant (PO1 HD-047609); $5,384,902 direct costs; 07/2005 - 06/2012.|
|Principal Investigator, Mitochondrial Genetic Determinants of Human Parturition and Fetal Growth. NIH/National Institute of Child Health and Human Development ARRA Supplement to Program Project Grant (PO1 HD-047609S); $500,001 direct costs; 09/2009 - 06/2012.|
|Co-Principal Investigator, U.S. National Children’s Study - Orange County, California (OCCA), Vanguard Center (James Swanson, PI). National Institutes of Health (HHSN-275200503415C); $14,682,364 total costs; 09/2005 - 06/2011.|
|Co-Principal Investigator, Preterm Birth in Nulliparous Women (Deborah A. Wing, PI). National Institutes of Health (U10 HD-063046); $1,368,052 total costs; 10/2009 - 09/2013.|
|Principal Investigator, Self-Reported Stress and Stress Biomarkers - Development of an Optimized Measure of Chronic Stress in Human Pregnancy: a National Children’s Study (NCS) Formative Research Project. NIH/ National Institute of Child Health and Human Development (HHSN-275200503415C); $924,861 direct costs; 10/2010 – 03/2012.|
|Principal Investigator, Self Report and Biological Measures of Maternal Stress Using Ecological Momentary Assessment (EMA) Methodology in Human Pregnancy: a NCS Formative Research Project. NIH/ National Institute of Child Health and Human Development (HHSN-275200503415C); $287,040 direct costs; 10/2010 – 03/2012.|
|Principal Investigator, Biological Moderators of Cortisol Activity in Human Pregnancy: a NCS Formative Research Project. NIH/ National Institute of Child Health and Human Development (HHSN-275200503415C); $382,141 direct costs; 10/2010 – 03/2012.|
|Co-Investigator, Long-term effects of early nutrition on later health Berthold Koletzko, PI) European Union Large Scale, Multinational, Collaborative Project (based at the University of Munich, Germany) (KBBE 2011.2.2-03) Euro 14,650,552 direct costs; 01/12 – 12/2017.|
|Co-Investigator, Stress during pregnancy and the developmental origins of renal disease in aboriginal Australians (Roger Smith, PI). Australian National Health and Medical Research Council; Australian $832,535 direct costs; 01/2009 - 12/2012.|
|Co-Investigator, The Iowa Flood Project: Effects of prenatal maternal stress on pregnancy outcomes and infant development (Suzanne King, PI). Canadian Institutes of Health Research (CIHR), Institute of Human Development, Child and Youth Health (CIHR FRN 93660); Canadian $1,800,000 direct costs; 07/2009 - 06/2014.|
|Consultant and Member, Scientific Advisory Board, Novel Interventions to Reduce Stress-Induced Non-Homeostatic Eating (Ellissa Epel and Nancy Adler, PIs). NIH/ National Heart, Lung and Blood Institute (UO1 HL-097973); $793,096 direct costs; 09/2009 - 06/2014.|
|Consultant, Course and Predictors of Depressive Relapse During In Vitro Fertilization (Marlene Freeman, PI), NIH/ National Institute of Mental Health R21 Project based at the Harvard Medical School Department of Psychiatry, Division of Perinatal and Reproductive Psychiatry (Massachusetts General Hospital), $ 375,000 direct costs, 07/12 – 06/2014.|
|Research Center||UC Irvine Development, Health and Disease Research Program|
|Link to this profile||http://www.faculty.uci.edu/profile.cfm?faculty_id=5140|