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 (below 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 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.
Early procedural pain is associated with regionally-specific alterations in thalamic development in preterm neonates
Journal of Neuroscience
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
Repeated exposure to sucrose for procedural pain in mouse pups leads to long-term widespread brain alterations
Cortisol levels in former preterm children at school age are predicted by neonatal procedural pain-related stress
Neonatal pain and infection relate to smaller cerebellum in very preterm children at school age
The Journal of pediatrics
Invasive procedures in preterm children: brain and cognitive development at school age
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
Internalizing behaviours in school-age children born very preterm are predicted by neonatal pain and morphine exposure
European Journal of Pain
Neonatal pain-related stress, functional cortical activity and visual-perceptual abilities in school-age children born at extremely low gestational age
Parent behaviors moderate the relationship between neonatal pain and internalizing behaviors at 18 months corrected age in children born very prematurely
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 - 2009Research Group Members
Evelyn Armour, Volunteer
Mary Beckingham, Research Assistant
Cecil Ming Yeung Chau, Research Manager
Connie Che, Research Nurse
Kenny Fok, Research Assistant
Vicki Goh, Research Nurse
Eddie Kwan, Visiting Scholar
Mia McLean, Postdoctoral Research Fellow
Nikoo Niknafs, Neonatology Fellow
Hannah Phillips, Graduate Student
Janet Rigney, Research Coordinator
Victoria Tapics, Research Respiratory Therapist
A career dedicated to relieving pain in the tiniest patients: Dr. Ruth Grunau recognized for outstanding accomplishments in the field of infant pain
At one time, many doctors and nurses believed that newborn babies couldn’t feel pain. Now we know that high levels of pain early in life can have lasting effects on the brain development and stress responses of babies born very preterm. This dramatic shift is due in part to the research of BC Children’s Hospital investigator Dr. Ruth Grunau who has dedicated her career to understanding and managing the effects of pain on young babies.