• 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 reactivity and neuro-development in preterm infants/children
  • Long term effects of early pain
  • Pain measurement
Summary
Early stress in immature infants, both animal and human, has the potential for long-term effects. Medical care of infants born prematurely at extremely low gestational ages (ELGA; < 29 weeks gestation) involves systematic repeated exposure to noxious procedures that frequently induce stress and pain. Pain in biologically immature neonates induces numerous physiologic, endocrine and behavioral changes that may contribute to changes in neuro-development - affecting pain systems, the ability to self-regulate behaviorally and physiologically, as well as affecting multiple aspects of attention, learning, and memory. These difficulties impact on the infant's adjustment to the environment, parent-infant interaction and later educational achievement, but their etiology is largely unknown. Using a biobehavioural interdisciplinary approach we have gained new knowledge about pain reactivity, and about relationships between response systems in vulnerable preterm, compared to healthy term born, babies.
Current Projects

The focus of my interdisciplinary research program is biobehavioural reactivity and infant neurodevelopment, broadly encompassing multiple aspects of infant arousal, self-regulation, attention and cognition in preterm and term born infants, including pain responses. This research program is currently funded by the Canadian Institutes of Health Research (CIHR), the National Institutes of Health (NIH, USA), with additional support from the Human Early Learning Partnership (HELP).

Clinical practice of pain management in the Neonatal Intensive Care Unit (NICU) has changed in recent years from no concern with pain to widespread use of analgesia and sedation, but there are major gaps in knowledge of pain assessment in immature infants, and in long term effects inherent to both pain itself, and varying exposure to 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 appear to reflect sleep/waking state, and are not stress cues. Currently we are exploring whether stress and pain responses can be differentiated in preterm infants, or whether they are on a continuum. We have shown that greater exposure to early pain in the NICU is associated subsequently with generally dampened pain responses, and that altered pain reactivity persists after discharge from hospital. Further, we have some preliminary evidence that morphine given to babies during the acute care phase in the NICU may ameliorate altered pain reactivity, but very little is known about the effects (negative or positive) of early opioid exposure on other aspects of neurodevelopment.

Pain in infants born at extremely low gestational age is developmentally "unexpected" and occurs at the time of most rapid brain development. In a series of longitudinal studies, we are evaluating changes in behavior, physiologic, and cortisol response (the primary human stress hormone), to varying physical stress and pain during hospitalization as a function of prior experience in the NICU, including early illness severity, pain and morphine exposure.

After NICU discharge we have a series of studies that grew from our earlier findings at ages 3, 4.5 and 9 years, that children born extremely low birthweight, compared to term born peers, displayed stress behaviors to cognitive challenges involving processing novelty. To explore the etiology, we are examining biobehavioral reactivity (behavior, physiologic, cortisol) to visual novelty in preterm compared to term born infants in home visits at 3 and 6 months, and in our lab in the Biobehavioural Research Unit at 8 months (ages corrected for prematurity). In addition to comparing responses of preterm and term born groups, among the preterm infants we are examining reactivity to visual novelty in relation to prior experience in the NICU. 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.

Recently we began a new study of behavioral, cardiac and hormonal (cortisol) reactivity to pain of immunization at 6 months CA comparing responses in preterm and term born infants.  Mother-infant interaction and stress reactivity as moderators of pain responses are also being examined.
 

Selected Publications

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. PMID: 21544009

Holsti L, Grunau RE, Shany E. Assessing acute pain in preterm infants in the NICU: 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):273-80. PMID: 21334150

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. PMID: 20974268

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):184-95. PMID: 21298633

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. PMID: 20664338

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. PMID: 20674931.

Holsti L, Grunau RE. Considerations for using sucrose to reduce procedural pain in preterm infants. Pediatrics, 2010;125(5):1042-1047. PMID: 20403938

Oberlander TF, Papsdorf M, Brain UM, Misri S, Ross C, Grunau, RE. Prenatal effects of selective serotonin reuptake inhibitor antidepressants, serotonin transporter promoter genotype (SLC6A4), and maternal mood on child behavior at 3 years of age. Archives of Pediatrics & Adolescent Medicine, 2010;164(5):444-451. PMID: 20439795

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. PMID: 19943040

Grunau RE. Long term effects of pain in infants. In: Schmidt, R.F, & Willis, W.D (Eds). Encyclopedic Reference of Pain. 2nd Ed. New York. Springer Berlin / Heidelberg, 2010.

Doesburg SM, Ribary U, Herdman AT, Cheung T, Moiseev A, Weinberg H, Whitfield MF, Synnes A, Liotti M, Weeks D, Grunau RE. Altered long-range phase synchronization and cortical activation in children born very preterm. In S. Supek and A. Sušac (Eds.): Advances in Biomagnetism – BIOMAG2010, IFMBE Proceedings 28, pp. 250–253, Springer Berlin Heidelberg, 2010.

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. PMID: 19307058

Grunau RE, Haley DW, Whitfield MF, Weinberg J, Yu W, Thiessen P. Altered basal cortisol levels at 3, 6, 8 and 18 months in infants born extremely low gestational age. J Pediatrics. 2007;150(2):151-156. PMID: 17236892

Grunau RE, Tu MT. Long-term consequences of pain in human neonates. In K.J.S. Anand, B.J. Stevens, & P.J. McGrath (Eds.) Pain in Neonates, 3rd edition. Amsterdam: Elsevier Science, 45-55, 2007.

Grants
Honours & Awards
Distinguished Scholar, Child & Family Research Institute, 2007 – present
Senior Scholar, Human Early Learning Partnership, 2007 - present
Senior Scholar, Michael Smith Foundation for Health Research, 2002-2007
Joint Research Scholar Award, BC Health Research Foundation and BC Research Institute for Children's & Women's Health, 1999-2002
Research Group Members
Ivan Cepeda, MD, MSc - Lab Manager
Gisela Gosse, RN, BScN - Research Nurse
Cecil Chau, MSc - Research Assistant
Mary Beckingham, BEd - Research Assistant
Sara Duncanson, MA - Psychometrician
Janet Kidd, BSc – Psychometrician
Jessica Trach, MA - Research Assistant
Jillian Vinall, MA - PhD student (Neuroscience)
Susanne Brummelete, PhD - Postdoctoral fellow
Jill Zwicker, PhD - Postdoctoral Fellow
Ayala Gover, MD - Research Fellow