fetal/developmental programming of health and disease risk, stress, pregnancy, fetal development, neurodevelopment, childhood obesity, maternal-placental-fetal neuroendocrine, immune, genetic, epigenetic, telomere, mitochondrial and stem cell biology.
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).
NIH/ National Institute of Child Health and Human Development – First Independent Research Support and Transition (FIRST) Award, (1998-2003).
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 (2005-2010).
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).
Member, Scientific Advisory Board, DAACRO Diagnostic Assessment and Clinical Research Organization, Trier, Germany (2011-2013).
Member, Scientific Advisory Board, MD2K Center of Excellence for Mobile Sensor Data-to-Knowledge, University of Memphis, Memphis, TN (2014-2019).
Member, Scientific Advisory Board, Children’s Environmental Health Center, University of Southern California, Los Angeles, CA (2015 – present)
Elected Fellow, Academy of Behavioral Medicine Research (2017)
The UC Irvine Development, Health and Disease Research Program is a transdisciplinary 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 (stress, nutrition) on outcomes related to fetal growth and maturation, birth phenotypes, and newborn, infant and child physical and mental health. Our studies focus on putative mechanisms involving maternal-placental-fetal endocrine, immune, vascular and genetic/epigenetic processes, including telomere, mitochondrial and stem cell biology.
Established in 2000, 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 36 faculty investigators directly funded by our program (of which 14 are based at UC Irvine and 22 at other institutions), along with several additional collaborators. We have primarily been conducting 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 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 and 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, iii) the role of maternal exposure to childhood trauma on the structural and functional development of the fetal/newborn brain; iv) the role of maternal social disadvantage in programming fetal cellular aging-related processes, with a focus on telomere and mitochondrial biology; and v) 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 own studies our program has established formal, funded collaborations with several other investigators and DOHaD-related projects in the U.S., Canada, Europe and Australia.
SELECTED REPRESENTATIVE PUBLICATIONS
Wadhwa PD. Psychoneuroendocrine processes in human pregnancy influence fetal development and health. Psychoneuroendocrinology, 2005, 30:724-743.
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.
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):513-8.
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: 632548.
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; 5(245):pt7.
Entringer S, Buss C, Wadhwa PD. Prenatal Stress, Telomere Biology, and Fetal Programming of Health and Disease Science Signaling, 2012; 5(248):pt12.
Fox M, Entringer S, Buss C, DeHaene J, Wadhwa PD. Intergenerational Transmission of the Effects of Acculturation on Health in Hispanic Americans: A Fetal Programming Perspective. American Journal of Public Health, 2015, 105 (3): S409-23.
Entringer S, Buss C, Wadhwa PD. Prenatal stress, development, health and disease risk: A psychobiological perspective. Psychoneuroendocrinology. 2015, 62:366-375.
Moog NK, Buss C, Entringer S, Shahbaba B, Gillen DL, Hobel CJ, Wadhwa PD. Maternal Exposure to Childhood Trauma Is Associated During Pregnancy with Placental-Fetal Stress Physiology. Biological Psychiatry. 2016, 79(10):831-839.
Ikenoue S, Waffarn F, Sumiyoshi K, Ohashi M, Ikenoue C, Buss C, Gillen DL, Simhan HN, Entringer S, Wadhwa PD. Association of ultrasound-based measures of fetal body composition with newborn adiposity. Pediatric Obesity. 2017 Aug;12 S1:86-93.
Entringer S, Buss C, Rasmussen JM, Lindsay K, Gillen DL, Cooper DM, Wadhwa PD. Maternal cortisol during pregnancy and infant adiposity: a prospective investigation. J Clin Endocrinol Metab. 2016 Dec 23: jc20163025.
Fox M, Thayer Z, Wadhwa PD. Assessment of acculturation in minority health research. Soc Sci Med. 2017 Mar; 176:123-132.
Esplin MS, Elovitz MA, Iams JD, Parker CB, Wapner RJ, Grobman WA, Simhan HN, Wing DA, Haas DM, Silver RM, Hoffman MK, Peaceman AM, Caritis SN, Parry S, Wadhwa P, Foroud T, Mercer BM, Hunter SM, Saade GR, Reddy UM; nuMoM2b Network. Predictive Accuracy of Serial Transvaginal Cervical Lengths and Quantitative Vaginal Fetal Fibronectin Levels for Spontaneous Preterm Birth Among Nulliparous Women. Journal of the American Medical Association (JAMA). 2017 Mar 14;317(10):1047-1056.
Ikenoue S, Waffarn F, Ohashi M, Sumiyoshi K, Ikenoue C, Buss C, Gillen DL, Simhan HN, Entringer S, Wadhwa PD. Prospective association of fetal liver blood flow at 30 weeks gestation with newborn adiposity. Am J Obstet Gynecol. 2017 Aug; 217(2): 204.e1-204.e8
Buss C, Entringer S, Moog NK, Toepfer P, Fair DA, Simhan HN, Heim CM, Wadhwa PD. Intergenerational Transmission of Maternal Childhood Maltreatment Exposure: Implications for Fetal Brain Development. J Am Acad Child Adolesc Psychiatry. 2017 May; 56(5):373-382.
Moog NK, Entringer S, Rasmussen JM, Styner M, Gilmore JH, Kathmann N, Heim CM, Wadhwa PD, Buss C. Intergenerational Effect of Maternal Exposure to Childhood Maltreatment on Newborn Brain Anatomy. Biological Psychiatry. 2018 83(2):120-127.
de Punder K, Heim C, Przesdzing I, Wadhwa PD, Entringer S. Characterization in humans of in vitro leucocyte maximal telomerase activity capacity and association with stress. Philosophical Transactions of the Royal Society B. 2018; 373(1741).
Entringer S, de Punder K, Buss C, Wadhwa PD. The fetal programming of telomere biology hypothesis: an update. Philosophical Transactions of the Royal Society B. 2018;373(1741).
Rudolph MD, Graham AM, Feczko E, Miranda-Dominguez O, Rasmussen JM, Nardos R, Entringer S, Wadhwa PD, Buss C, Fair DA. Maternal IL-6 during pregnancy can be estimated from newborn brain connectivity and predicts future working memory in offspring. Nature Neuroscience. 2018 May;21(5):765-772.
Lindsay KL, Buss C, Wadhwa PD, Entringer S. The Interplay Between Nutrition and Stress in Pregnancy: Implications for Fetal Programming of Brain Development. Biological Psychiatry. 2019 Jan 15;85(2):135-149.
Czamara D, Eraslan G, Page CM, Lahti J, Lahti-Pulkkinen M, Hämäläinen E, Kajantie E, Laivuori H, Villa PM, Reynolds RM, Nystad W, Håberg SE, London SJ, O'Donnell KJ, Garg E, Meaney MJ, Entringer S, Wadhwa PD, Buss C, Jones MJ, Lin DTS, MacIsaac JL, Kobor MS, Koen N, Zar HJ, Koenen KC, Dalvie S, Stein DJ, Kondofersky I, Müller NS, Theis FJ; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Räikkönen K, Binder EB. Integrated analysis of environmental and genetic influences on cord blood DNA methylation in newborns. Nature Communications. 2019 Jun 11; 10(1):2548.
Lazarides C, Epel ES, Lin J, Blackburn EH, Voelkle MC, Buss C, Simhan HN, Wadhwa PD, Entringer S. Maternal pro-inflammatory state during pregnancy and newborn leukocyte telomere length: A prospective investigation. Brain Behav Immun. 2019 Aug; 80:419-426.
McEwen LM, O'Donnell KJ, McGill MG, Edgar RD, Jones MJ, MacIsaac JL, Lin DTS, Ramadori K, Morin A, Gladish N, Garg E, Unternaehrer E, Pokhvisneva I, Karnani N, Kee MZL, Klengel T, Adler NE, Barr RG, Letourneau N, Giesbrecht GF, Reynolds JN, Czamara D, Armstrong JM, Essex MJ, de Weerth C, Beijers R, Tollenaar MS, Bradley B, Jovanovic T, Ressler KJ, Steiner M, Entringer S, Wadhwa PD, Buss C, Bush NR, Binder EB, Boyce WT, Meaney MJ, Horvath S, Kobor MS. The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells. Proceedings of the National Academy of Sciences USA. 2019 Oct 14. pii: 201820843 [Epub ahead of print].
Lindsay KL, Entringer S, Buss C, Wadhwa PD. Intergenerational transmission of the effects of maternal exposure to childhood maltreatment on offspring obesity risk: A fetal programming perspective. Psychoneuroendocrinology. 2020 Mar 23; 116:104659.
Gyllenhammer LE, Entringer S, Buss C, Wadhwa PD. Developmental programming of mitochondrial biology: a conceptual framework and review. Proc Royal Soc - Biol Sci. 2020 May 13;287(1926): 20192713. doi: 10.1098/rspb.2019.2713. PMID: 32345161.
Scholaske L, Buss C, Wadhwa PD, Entringer S. Maternal subjective social standing is related to inflammation during pregnancy. Brain Behav Immun. 2020 Aug;88:711-717. doi:10.1016/j.bbi. 2020.05.023. Epub 2020 May 7. PMID: 32389699.
Oliver A, LaMere B, Weihe C, Wandro S, Lindsay KL, Wadhwa PD, Mills DA, Pride DT, Fiehn O, Northen T, de Raad M, Li H, Martiny JBH, Lynch S, Whiteson K. Cervicovaginal Microbiome Composition Is Associated with Metabolic Profiles in Healthy Pregnancy. mBio. 2020 Aug 25;11(4):e01851-20. doi:10.1128/mBio.01851-20. PMID: 32843557.
Verner G, Epel E, Lahti-Pulkkinen M, Kajantie E, Buss C, Lin J, Blackburn E, Räikkönen K, Wadhwa PD, Entringer S. Maternal Psychological Resilience During Pregnancy and Newborn Telomere Length: A Prospective Study. Am J Psychiatry. 2020 Sep 11: appiajp202019101003. doi: 10.1176/ appi.ajp.2020.19101003. Epub ahead of print. PMID: 32911996.
Lazarides C, Ward EB, Buss C, Chen WP, Voelkle MC, Gillen DL, Wadhwa PD, Entringer S. Psychological stress and cortisol during pregnancy: An ecological momentary assessment (EMA)-Based within- and between-person analysis. Psychoneuroendocrinology. 2020 Nov;121:104848. doi: 10.1016/ j.psyneuen.2020.104848. PMID: 32927180.
Gyllenhammer LE, Entringer S, Buss C, Simhan HN, Grobman WA, Adam EK, Keenan-Devlin L, Borders AE, Wadhwa PD. Prospective association of maternal immune pro-inflammatory responsivity and regulation in pregnancy with length of gestation. Am J Reprod Immunol. 2020 Oct 25:e13366. doi: 10.1111/aji.13366. Epub ahead of print. PMID: 33099840.
Ikenoue S, Waffarn F, Ohashi M, Tanaka M, Gillen DL, Buss C, Entringer S, Wadhwa PD. Placental corticotrophin releasing hormone is a modulator of fetal liver blood perfusion. J Clin Endocrinol Metab. 2020 Dec 12:dgaa908. doi: 10.1210/clinem/dgaa908. Epub ahead of print. PMID: 33313841.
Principal Investigator, “Gene-Environment Interactions in Human Parturition” NIH/National Institute of Child Health and Human Development
Program Project (P01 HD-047609); $5,384,902 direct costs; 07/2005 - 06/2012.
Principal Investigator “Ecological Momentary Assessment (EMA) of Biobehavioral Processes in Human Pregnancy” NIH/National Institute of Child Health and Human Development (R01 HD-060628); $2,364,828 direct costs; 02/2010 - 01/2016.
Principal Investigator (with Sonja Entringer) “Prenatal Stress Biology, Infant Body Composition and Obesity Risk” NIH/ National Institute of Child Health and Human Development (R01 HD-065825); $1,965,485 direct costs; 07/2010 – 06/2016.
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; 12/2010-11/2016.
Principal Investigator (with Claudia Buss, Hyagriv Simhan) “Intergenerational Effects of Maternal Childhood Trauma on the Fetal Brain” NIH/National Institute of Mental Health (R01 MH-105538); $2,488,650 direct costs; 04/2015 - 03/2021.
Principal Investigator, “Maternal acculturation during pregnancy and newborn and infant adiposity in Mexican-Americans” NIH/ National Institute on Minority Health and Health Disparities (R01 MD-010738); $2,490,855 direct costs; 07/2016 – 06/2021.
Principal Investigator (with Sonja Entringer, Hyagriv Simhan, Elissa Epel) “Social disadvantage and fetal programming of the telomere biology system” NIH/ National Institute on Aging (R01 AG-050455); $2,385,400 direct costs; 09/2016 – 08/2021.
Principal Investigator (with Claudia Buss, Richard Miller, Thomas O’Connor, Hyagriv Simhan) “Pre- and postnatal exposure periods for child health: common risks and shared mechanisms” NIH/ Office of the Director, Environmental Influences on Child Health Outcomes (ECHO) Program (UG3/UH3 OD-023349); $12,132,084 direct costs
09/2016 – 03/2023.
UC Irvine Development, Health and Disease Research Program