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Updated: May 6, 2026
A Preterm Rat Model for Pain Studies
Published on: February 9, 2024
Neonatal pain-related stress predicts cortical thickness at age 7 years in children born very preterm
Manon Ranger1, Cecil M Y Chau, Amanmeet Garg
1Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada ; Developmental Neurosciences and Child Health, Child and Family Research Institute, Vancouver, British Columbia, Canada.
Insights
Neonatal pain-related stress in very preterm infants is linked to thinner cortical thickness at school age. This association persists even after accounting for other prematurity-related clinical factors.
Area of Science:
- Neuroscience
- Developmental Pediatrics
- Medical Imaging
Background:
- Children born very preterm exhibit altered brain development, including reduced gray and white matter volumes and thinner cortex.
- Neonatal pain-related stress is a potential etiological factor in these developmental changes.
- Previous research indicated neonatal pain stress is associated with atypical brain development from birth to term-equivalent age.
Purpose of the Study:
- To investigate the association between neonatal pain-related stress and cortical thickness at school age in very preterm children.
- To adjust for clinical confounders of prematurity in this analysis.
Main Methods:
- Longitudinal study of 42 very preterm children (24-32 weeks gestational age) with 3-D T1 MRI at ~7.9 years.
- Exclusion of children with severe brain injury or major impairments.
- Cortical thickness calculated using FreeSurfer; association with pain-related stress (number of skin-breaking procedures) analyzed using constrained principal component analysis and generalized linear modeling, controlling for clinical factors.
Main Results:
- Greater neonatal pain-related stress was significantly associated with thinner cortex in 21 out of 66 cerebral regions.
- These thinner cortical regions were predominantly located in the frontal and parietal lobes.
- The association remained significant after correcting for multiple comparisons and adjusting for neonatal clinical factors.
Conclusions:
- Neonatal pain-related stress is associated with thinner cortex in multiple brain regions at school age in very preterm children.
- This finding holds true even in children without major sensory, motor, or cognitive impairments.
- The results suggest pain-related stress is an independent risk factor for altered cortical development in this population.
Background:
Altered brain development is evident in children born very preterm (24-32 weeks gestational age), including reduction in gray and white matter volumes, and thinner cortex, from infancy to adolescence compared to term-born peers. However, many questions remain regarding the etiology. Infants born very preterm are exposed to repeated procedural pain-related stress during a period of very rapid brain development. In this vulnerable population, we have previously found that neonatal pain-related stress is associated with atypical brain development from birth to term-equivalent age. Our present aim was to evaluate whether neonatal pain-related stress (adjusted for clinical confounders of prematurity) is associated with altered cortical thickness in very preterm children at school age.
Methods:
42 right-handed children born very preterm (24-32 weeks gestational age) followed longitudinally from birth underwent 3-D T1 MRI neuroimaging at mean age 7.9 yrs. Children with severe brain injury and major motor/sensory/cognitive impairment were excluded. Regional cortical thickness was calculated using custom developed software utilizing FreeSurfer segmentation data. The association between neonatal pain-related stress (defined as the number of skin-breaking procedures) accounting for clinical confounders (gestational age, illness severity, infection, mechanical ventilation, surgeries, and morphine exposure), was examined in relation to cortical thickness using constrained principal component analysis followed by generalized linear modeling.
Results:
After correcting for multiple comparisons and adjusting for neonatal clinical factors, greater neonatal pain-related stress was associated with significantly thinner cortex in 21/66 cerebral regions (p-values ranged from 0.00001 to 0.014), predominately in the frontal and parietal lobes.
Conclusions:
In very preterm children without major sensory, motor or cognitive impairments, neonatal pain-related stress appears to be associated with thinner cortex in multiple regions at school age, independent of other neonatal risk factors.
