• Biobehavioural regulation, brain and neurodevelopment in premature infants and children
• Long term effects of neonatal pain on stress regulation, brain, behavior, cognitive and motor development
• Infant pain and stress
• Parenting stress, parent-infant interaction
• Effects of analgesia and sedation on neurodevelopment and behavior

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.

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.

*Trainee supervised by 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.

Synnes AR, Anson S, Arkesteijn A, Butt A, Shelagh S, Grunau RE, Rogers M, Whitfield MF. School Entry Age Outcomes for ≤ 800 Gram Birth Weight Babies. Journal of Pediatrics, 2010;157(6):989-994.e1. 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.

*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;54(4):383-400.

*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 infants. In: Schmidt, R.F, & Willis, W.D (Eds). Encyclopedic Reference of Pain.3nd Ed. New York. Springer Berlin / Heidelberg.

Grunau RE (in press). 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.

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

Ivan Cepeda, MD, MSc - Lab Manager
Mary Beckingham, BEd - Research Assistant
Sandy Belanger, RN – Research Nurse
Janet Rigney, Research Co-ordinator
Mark Chalmers, - BSc Respiratory Therapist
Sara Duncanson, MA - Psychometrician
Janet Kidd, BSc – Psychometrician
Jessica Trach, MA - Research Assistant
Manon Ranger, PhD - Postdoctoral fellow
Jill Zwicker, PhD - Postdoctoral Fellow
Teresa Cheung, PhD – Post-doctoral Fellow
Jillian Vinall, MA - PhD student (Neuroscience)
Cecil Chau, MSc - PhD student (Neuroscience)