• Grunau, Ruth Eckstein

    Titles

    Senior Scientist, CFRI
    Professor, Division of Neonatology, Department of Pediatrics, and Associate Member, Department of Psychology, University of British Columbia

    Degrees / Designations
    PhD, RPsych
    Primary Area of Research
    Developmental Neurosciences & Child Health
    Secondary Area(s) of Research
    Phone
    604-875-2447
    Fax
    604-875-2384
    Lab Phone
    604-875-3160
    Assistant
    Gisela Gosse
    Assistant Phone
    604-875-2000 ext. 6978
    Mailing Address
    Developmental Neurosciences & Child Health
    F605B, 4480 Oak Street
    Vancouver, BC V6H 3V4
    Affiliate Websites
    Research Areas
    • Biobehavioural regulation, brain and neurodevelopment in premature infants and children 
    • Long-term effects of neonatal pain on stress regulation, brain, behavior, neurodevelopment 
    • Infant pain and stress 
    • Parenting stress, parent-infant interaction

    Summary

    Early stress in immature neonates, both animal and human, has the potential for long-term effects. Medical care of infants born prematurely at very low gestational age (< 33 weeks gestation) involves repeated exposure to noxious procedures, at a time of very rapid brain development and programming of stress systems. 

    Pain in biologically immature neonates is developmentally “unexpected” inducing numerous physiologic, endocrine and behavioral changes that may contribute to altered brain development and stress regulation - affecting neurodevelopment, ability to self-regulate behaviorally and physiologically, as well as altering multiple aspects of attention, learning and memory. These difficulties impact the infant's adjustment to the environment, parent-infant interaction, behavior and later academic achievement; however the etiology is largely unknown. 

    Using a transdisciplinary, biobehavioural approach we have gained new knowledge about pain reactivity, relationships between response systems in premature compared to healthy term born infants, and increased understanding of mechanisms contributing to altered neurodevelopment and internalizing behaviors in these fragile children.

    Current Projects

    The focus of my transdisciplinary research program is biobehavioural reactivity and infant neurodevelopment, broadly encompassing multiple aspects of infant arousal, self-regulation, attention, cognition and brain development in preterm and term born infants. My research program is currently funded by the National Institutes of Health (NIH, USA) and the Canadian Institutes of Health Research (CIHR).

    Clinical practice of pain management in neonatal intensive care Unit (NICU) changed over the years  from no concern with pain to widespread use of analgesia and sedation, however there are major gaps in knowledge of pain assessment in immature infants, and in long term effects of pain-related stress and pain medications. With the goal to improve pain assessment, we recently confirmed that, along with recognized facial and heart rate changes, there are motor stress behaviors unique to premature infants (e.g. backward splaying of fingers). Conversely, other behaviors such as twitches and startles reflect sleep/waking state, and do not appear to be stress or pain cues. We have shown that greater exposure to neonatal pain-related stress in the NICU (adjusted for multiple medical and neonatal confounding factors) is associated with altered brain microstructure, cortico-spinal tract development, cortical thinning and resting oscillatory activity, stress hormone (cortisol) expression, cognitive development and internalizing behaviors, in infancy and at school-age. Importantly, greater morphine exposure does not appear to prevent adverse long term sequelae, and may impair cerebellar growth.

    In two longitudinal cohorts followed since birth, we build on our extensive neonatal medical and nursing data to examine behavior, neurodevelopment, stress regulation, parent-infant interaction at multiple ages from infancy to school-age. Further, in collaboration with the Child and Family Brain Imaging Facility and Brain mapping Unit, our group undertakes brain imaging (MRI, DTI), and in collaboration with Simon Fraser University - magnetoencephalography (MEG) at school-age. Furthermore, we are studying to what extent caregiver interaction style and parenting stress may modify infant behavior, as well as ameliorate or exacerbate effects of early stress/pain experience in preterm infants.

    In collaboration with geneticists in CFRI, we are beginning to address gene X environment (early stress) interactions, as well as epigenetics.

    Selected Publications

    *Trainee supervised by Dr. Grunau

    Grunau RE, Whitfield MF, Petrie-Thomas J, Synnes A, Cepeda IL, Keidar A, Rogers M, MacKay M, Hubber-Richard P, Johannesen D. Neonatal pain, parenting stress and interaction, in relation to cognitive and motor development at 8 and 18 months in preterm infants. Pain, 2009; 143:138–146.

    *Doesburg SM, Herdman AT, Ribary U, Cheung T, Moiseev A, Weinberg H, Liotti M, Weeks D, Grunau RE. Long-range synchronization and local desynchronization of alpha oscillations during visual short-term memory retention in children. Experimental Brain Research, 2010;201(4):719-727.

    Holsti L, Grunau RE. Considerations for using sucrose to reduce procedural pain in preterm infants. Pediatrics, 2010;125(5):1042-1047.

    Grunau RE, *Tu MT, Whitfield MF, Oberlander TF, Weinberg J, Yu W, Thiessen P, Gosse G, Scheifele D. Cortisol, behavior and heart rate reactivity to immunization pain at 4 months corrected age in infants born very preterm. Clinical Journal of Pain, 2010;26 (8):698-704.

    *Doesburg SM, Ribary U, Herdman AT, Miller SP, Poskitt KJ, Moiseev A, Whitfield MF, Synnes A, Grunau RE. Altered long-range alpha-band synchronization during visual short-term memory retention in children born very preterm. Neuroimage, 2011; 54(3): 2330-2339.

    *Brummelte S, Grunau RE, Zaidman-Zait A, Weinberg J, Nordstokke D, Cepeda IL. Cortisol levels in relation to maternal interaction and child internalizing behavior in preterm and full term children at 18 months corrected age. Developmental Psychobiology, 2011; 53(2):184-195.

    Holsti L, Grunau RE, Shany E.  Assessing pain in preterm infants in the neonatal intensive care unit: moving to a “brain-oriented” approach. Pain Management, 2011;1(2), 171–179.

    *Brummelte S, Grunau RE, Synnes AR, Whitfield MF, Petrie-Thomas J. Declining cognitive development from 8 to 18 months in preterm children predicts persisting higher parenting stress. Early Human Development, 2011;87(4):273-280.

    *Doesburg SM, Ribary U, Herdman AT, Moiseev A, Cheung T, Miller SP, Poskitt K, Weinberg H, Whitfield MF, Synnes A, Grunau RE. Magnetoencephalography reveals slowing of resting peak oscillatory frequency in children born very preterm. Pediatric Research, 2011;70(2):171-175.

    Schmidt B, Anderson P, Doyle L, Dewey D, Grunau R, Asztalos E, Davis P, Tin W, Moddemann D, Solimano A, Ohlsson A, Barrington K, Roberts R. Five-Year Follow-Up of Participants in the International Caffeine for Apnea of Prematurity Trial. JAMA, 2012;307(3):275-282.

    *Brummelte S, Grunau RE, Chau V, Poskitt KJ, Brant R, Vinall J, Gover A, Synnes A, Miller SP. Procedural pain and brain development in premature newborns. Annals of Neurology, 2012;71(3):385-96.

    *Gover A, Brummelte S, Synnes A, Miller SP, Brant R, Weinberg J, Whitfield MF, Grunau RE. A single course of antenatal steroids did not alter resting cortisol in very preterm infants to 18 months corrected age. Acta Paediatrica, 2012;101(6):604-8.

    *Vinall J, Miller SP, Chau V, *Brummelte S, Synnes A, Grunau RE. Neonatal pain in relation to postnatal growth in infants born very preterm. Pain, 2012;153(7):1374-81.

    *Zwicker JG, Grunau RE, Adams E, Chau V, Brant R, Poskitt KJ, Synnes A, Miller SP. Score for Neonatal Acute Physiology-II and neonatal pain predict corticospinal tract development in premature newborns. Pediatric Neurology, 2013;48:123-129.

    *Vinall, J, Grunau, RE, Brant R, Chau V, Poskitt K, Synnes AR, Miller SP. Slower postnatal growth is associated with delayed cerebral cortical maturation in preterm newborns. Science Translational Medicine, 2013;5(168):168ra8.

    Grunau RE (2013). Long-term effects of pain in children. In W. Zempsky, B. Stevens, P. McGrath, S. Walker (Eds.) Oxford Textbook of Paediatric Pain, Oxford University Press, Oxford UK.

    *Petrie Thomas J, Grunau RE, Oberlander T, Synnes A, Whitfield M. Focused Attention, Heart Rate Deceleration and Cognitive Development in Preterm and Full-Term Infants. Developmental Psychobiology, 2012 May;54(4):383-400

    *Gover A, Chau V, Miller SP, Brant R, McFadden DE, Poskitt KJ, Synnes A, Weinberg J, Grunau RE. Prenatal and postnatal inflammation in relation to cortisol levels in preterm infants at 18 months corrected age. Journal of Perinatology. 2013 Aug;33(8):647-51.

    Grunau RE, Cepeda IL, *Chau CMY, *Brummelte S, Weinberg J, Lavoie P, Ladd M, Hirschfeld AF, Russell E, Koren G, Van Uum S, Brant R, Turvey SE. Neonatal Pain-Related Stress and NFKBIA Genotype Are Associated with Altered Cortisol Levels in Preterm Boys at School Age. PLoS ONE. 2013 Sep 8(9): e73926. doi:10.1371/journal.pone.0073926.

    *Vinall J, Miller SP, Synnes AR, Grunau RE. Parent behaviors moderate the relationship between neonatal pain and internalizing behaviors at 18 months corrected age in children born very prematurely. Pain. 2013 Sep;154(9):1831-1839.

    *Doesburg SM, *Chau CM, Cheung TP, Moiseev A, Ribary U, Herdman AT, Miller SP, Cepeda IL, Synnes A, Grunau RE. Neonatal pain-related stress, functional cortical activity and visual-perceptual abilities in school-age children born at extremely low gestational age. Pain. Oct 2013 154(10), 1946-1952

    *Ranger M, *Chau CM, Garg A, Woodward TS, Beg MF, Bjornson B, Poskitt K, Fitzpatrick K, Synnes AR, Miller SP, Grunau RE. Neonatal Pain-Related Stress Predicts Cortical Thickness at Age 7 Years in Children Born Very Preterm. PLoS ONE. 2013 Oct;8(10): e76702. doi:10.1371/journal.pone.0076702

    Grunau RE. Neonatal pain in very preterm infants: Long-term effects on brain, neurodevelopment and pain reactivity. Rambam Maimonides Medical Journal. 2013 Oct;4(4): e0025. doi: 10.5041/RMMJ.10132.

    Doesburg SM, Moiseev A, Herdman AT, Ribary U, Grunau RE. Region-specific slowing of alpha oscillations is associated with visual-perceptual abilities in children born very preterm. Frontiers in Human Neuroscience. 2013 Nov;7:791. doi: 10.3389/fnhum.2013.00791.

    *Maimon N, Grunau RE, Cepeda IL, Friger M, Selnovik L, Gilat S, Shany E. Electroencephalographic Activity in Response to Procedural Pain in Preterm Infants Born at 28 and 33 Weeks Gestational Age. Clinical Journal of Pain, Clin J Pain. 2013 Dec;29(12):1044-1049.

    *Ranger M, Synnes AR, *Vinall J, Grunau RE. Internalizing behaviours in school-age children born very preterm are predicted by neonatal pain and morphine exposure. European Journal of Pain. Published online 2013 Dec. doi: 10.1002/j.1532-2149.2013.00431.x.

    *Ranger M, Grunau RE. Early repetitive pain in preterm infants in relation to the developing brain. Pain Management, 2014 Jan; 4(1):57-67.

    *Vinall J, Grunau RE. Impact of repeated procedural pain-related stress in infants born very preterm. Pediatric Research. Published online, 2014 Feb. doi:10.1038/pr.2014.16

    McPherson C, Grunau RE. Neonatal pain control and neurologic effects of anesthetics and sedatives in preterm infants. Clinics in Perinatology, 2014 Mar;41(1):209-27.

    *Vinall J, Miller SP, Bjornson BH, Fitzpatrick KPV, Poskitt KJ, Brant R, Synnes AR, Cepeda IL, Grunau RE. Invasive procedures in preterm children: brain and cognitive development at school age. Pediatrics, 2014 Mar;133(3):412-21. 

    Grants
    CIHR Operating Grant – Project: "Analgesia and sedation in the preterm neonate: brain development and outcome" (2014-2020)
    Honours & Awards

    • Joint Research Scholar Award, BC Health Research Foundation & BC Research Institute for Children's & Women's Health, 1999 - 2001
    • Senior Scholar, Michael Smith Foundation for Health Research, 2001 - 2006 
    • Senior Scholar, Human Early Learning Partnership, 2007 - 2009
    • Senior Scientist, Child & Family Research Institute, 2002 - present

    Research Group Members
    Ivan Cepeda, MD, MSc - Lab Manager
    Mary Beckingham, BEd - Research Assistant 
    Manon Ranger, PhD - Postdoctoral fellow 
    Jillian Vinall, MA - PhD student Neuroscience
    Cecil Chau, MSc - PhD student Neuroscience