Overview

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 (

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 may 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.

Publications

Early procedural pain is associated with regionally-specific alterations in thalamic development in preterm neonates
Journal of Neuroscience
Duerden, Emma G and Grunau, Ruth E and Guo, Ting and Foong, Justin and Pearson, Alexander and Au-Young, Stephanie and Lavoie, Raphael and Chakravarty, M Mallar and Chau, Vann and Synnes, Anne and others
2018

The Val66Met brain-derived neurotrophic factor gene variant interacts with early pain exposure to predict cortisol dysregulation in 7-year-old children born very preterm: implications for cognition
Neuroscience
Chau, Cecil MY and Cepeda, Ivan L and Devlin, Angela M and Weinberg, Joanne and Grunau, Ruth E
2017

Repeated exposure to sucrose for procedural pain in mouse pups leads to long-term widespread brain alterations
Pain
Tremblay, Sophie and Ranger, Manon and Chau, Cecil MY and Ellegood, Jacob and Lerch, Jason P and Holsti, Liisa and Goldowitz, Daniel and Grunau, Ruth E
2017

Cortisol levels in former preterm children at school age are predicted by neonatal procedural pain-related stress
Psychoneuroendocrinology
Brummelte, Susanne and Chau, Cecil MY and Cepeda, Ivan L and Degenhardt, Amanda and Weinberg, Joanne and Synnes, Anne R and Grunau, Ruth E
2015

Neonatal pain and infection relate to smaller cerebellum in very preterm children at school age
The Journal of pediatrics
Ranger, Manon and Zwicker, Jill G and Chau, Cecil MY and Park, Min Tae M and Chakravarthy, M Mallar and Poskitt, Kenneth and Miller, Steven P and Bjornson, Bruce H and Tam, Emily WY and Chau, Vann and others
2015

Invasive procedures in preterm children: brain and cognitive development at school age
Pediatrics
Vinall, Jillian and Miller, Steven P and Bjornson, Bruce H and Fitzpatrick, Kevin PV and Poskitt, Kenneth J and Brant, Rollin and Synnes, Anne R and Cepeda, Ivan L and Grunau, Ruth E
2014

Neonatal pain and COMT Val158Met genotype in relation to serotonin transporter (SLC6A4) promoter methylation in very preterm children at school age
Frontiers in behavioral neuroscience
Chau, Cecil MY and Ranger, Manon and Sulistyoningrum, Dian and Devlin, Angela M and Oberlander, Tim F and Grunau, Ruth E
2014

Internalizing behaviours in school-age children born very preterm are predicted by neonatal pain and morphine exposure
European Journal of Pain
Ranger, M and Synnes, AR and Vinall, J and Grunau, RE
2014

Neonatal pain-related stress, functional cortical activity and visual-perceptual abilities in school-age children born at extremely low gestational age
PAIN®
Doesburg, Sam M and Chau, Cecil M and Cheung, Teresa PL and Moiseev, Alexander and Ribary, Urs and Herdman, Anthony T and Miller, Steven P and Cepeda, Ivan L and Synnes, Anne and Grunau, Ruth E
2013

Parent behaviors moderate the relationship between neonatal pain and internalizing behaviors at 18 months corrected age in children born very prematurely
PAIN®
Vinall, Jillian and Miller, Steven P and Synnes, Anne R and Grunau, Ruth E
2013

Research

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.

Grants

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

CIHR Operating Grant - Project: "Stress, Brain and Neurodevelopment in Children Born Preterm" (2018-2022)

Honours & Awards

Jeffrey Lawson Award for Advocacy in Children’s Pain Relief, American Pain Society 2018

Rovee-Collier Mentor Award, International Society for Developmental Psychobiology, 2018

Outstanding Pain Mentorship Award, Canadian Pain Society 2019

Distinguished Career Award, International Association for the Study of Pain SIG Pain in Childhood 2019

Senior Scholar, Michael Smith Foundation for Health Research, 2001 - 2006

Senior Scholar, Human Early Learning Partnership, 2007 - 2009

Research Group Members

Mary Beckingham, Research Assistant
Mark Bichin, Doctoral Student
Cecil Ming Yeung Chau, Research Manager
Connie Che, Research Nurse
Kenny Fok, Research Assistant, Undergraduate Student
Vicki Goh, Research Nurse
Shanlea Gordon, Research Co-ordinator
Terri Levine, Postdoctoral Fellow
Mia McLean, Visiting PhD:Visiting PhD
Nikoo Niknafs, Neonatology Fellow
Chandra Pham
Hannah Phillips, Graduate Student
Janet Rigney, Research Coordinator
Victoria Tapics, Research Respiratory Therapist
Jasmine Wong, Graduate Research Asst