Research co-led by SickKids shows premature babies may be more susceptible to effects of pain from lifesaving care, harming brain development

Posted on January 30, 2018

Summary:

Co-principal investigator Dr. Steven Miller, Head of Neurology and Senior Scientist in Neurosciences & Mental Health at SickKids, and lead author Dr. Emma Duerden, Senior Research Associate in Neurology discuss their research on the memory of pain in early brain development.

Extremely preterm babies, those born at less than 28 weeks of gestation, are often critically ill around the time of birth and as a part of lifesaving care can receive hundreds of painful procedures.

In a new study, researchers from The Hospital for Sick Children (SickKids), B.C. Women’s Hospital & Health Centre and BC Children’s Hospital found that the memory of this pain has a negative impact on early brain development.

We sat down with co-principal investigator Dr. Steven Miller, Head of Neurology and Senior Scientist in Neurosciences & Mental Health at SickKids, and lead author Dr. Emma Duerden (right), Senior Research Associate in Neurology, to discuss their research, published online Jan. 24 in The Journal of Neuroscience.

What is the connection between pain and brain development?

Our research shows that pain is associated with slower brain maturation. We wanted to determine whether the brains of the youngest preterm babies were at greatest risk and if there were specific brain regions that were more vulnerable. The results of our study suggest that the brains of babies born at the youngest gestational ages may be more susceptible to the effects of pain, irrespective of contemporary pain management. The brain changes associated with pain were themselves associated with adverse cognitive and motor functioning in the third year of life. These findings indicate that the memory of early pain outlasts the newborn period.

Using magnetic resonance imaging to study brain growth in very preterm babies we found that a specialized region of the brain (red), the thalamus (involved in relaying pain and touch information to the brain) showed a decrease in size (blue-purple) in those babies exposed to more painful procedures. Further, babies born at less than 28 weeks of gestation had the most pronounced changes in the thalamus.

What is the significance of these findings?

The results are the first in humans to provide evidence of a sensitive window for pain exposure and to confirm previous findings in experimental animal models. The location of the brain changes lend further weight to the suggestion that early pain is associated with disruptions in the development of the key pathways involved in pain and touch information.

Were you surprised by the results?

Previous animal research had indicated that exposure to painful stimuli resulted in different behavioural responses to pain depending on when the animals received the pain relative to their gestational age at birth. Our results indicating that the brain of extremely preterm babies may be more vulnerable to pain in comparison to babies born closer to term are consistent with previous animal studies.

What are the implications of your findings? Are there clinical applications that can be applied in the next few years?

Minimizing painful procedures in extremely preterm babies may be an opportunity to promote brain health and improve outcomes. Invasive procedures should be minimized in extremely preterm babies and finding pain-management strategies that promote brain development should be prioritized.

How did you assess the babies in your research?

MRI brain imaging was performed on the babies at around the time of birth and again at the babies’ due dates at B.C. Children’s Hospital. The neuroimaging techniques that we used provided information about the development of the sensorimotor system, the parts of our brain responsible for sensations on our skin and movement. By having two scans this allowed us to examine how painful procedures impacted the growth of the sensorimotor system.

The babies were followed through early childhood with testing to assess cognitive and motor function. By having long-term follow-up information about the babies’ cognitive and motor function, we were able to assess how early brain growth was associated with later motor abilities and higher-order thinking abilities.

What led you to pursue this question?

Neonatal care practices vary worldwide. Our overall goal is to inform the delivery of neonatal intensive care in ways that promote optimal brain development and enhance the outcomes of babies born preterm. In some international neonatal intensive care units, efforts are made to minimize invasive procedures for extremely preterm babies. However, no previous study with infants had provided clinical evidence for minimizing invasive procedures for young gestational ages.

What are the next steps for this research?

The infants are being followed to school age with MRI and neuropsychological testing. The next steps of our research are to examine if early stressors like pain are associated with academic ability and how we can promote long-term healthy outcomes in children born extremely preterm.