Related Experiment Video
Updated: Feb 17, 2026
A Preterm Rat Model for Pain Studies
Published on: February 9, 2024
Procedural pain and oral glucose in preterm neonates: brain development and sex-specific effects
Juliane Schneider1,2, Emma G Duerden1, Ting Guo1
1Department of Paediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Insights
Neonatal procedural pain and glucose exposure negatively impact preterm infant brain development, particularly in females, leading to poorer neurodevelopmental outcomes. Glucose did not mitigate pain
Area of Science:
- Neonatal neuroscience
- Developmental psychology
- Pediatric neuroimaging
Background:
- Premature infants experience significant procedural pain and glucose exposure in the NICU.
- Early life stress can impact brain development and long-term neurodevelopmental outcomes.
- Sex differences in brain development and vulnerability to environmental factors are increasingly recognized.
Purpose of the Study:
- To investigate the differential impact of procedural pain and glucose exposure on structural and functional brain development in preterm males and females.
- To assess the association between early pain and glucose exposure with neurodevelopmental outcomes at 18-month corrected age.
- To determine if glucose administration mitigates the adverse effects of pain on brain development.
Main Methods:
- Serial MRI scans (T1-weighted and resting-state functional MRI) were performed on 51 very preterm neonates at multiple time points.
- Brain volumes (thalamus, basal ganglia, total brain) were segmented, and functional connectivity was analyzed.
- Procedural pain was quantified by the number of invasive procedures, and neurodevelopment was assessed using the Bayley Scales of Infant Development.
- Generalized estimating equations were used to analyze the associations.
Main Results:
- Increased procedural pain was independently associated with slower growth in thalamic, basal ganglia, and total brain volumes, especially in females.
- Similar negative associations were found between glucose exposure and brain volumes.
- Functional connectivity between the thalamus and sensorimotor cortices was negatively correlated with the number of invasive procedures.
- Greater procedural pain and higher glucose exposure were linked to poorer neurodevelopmental outcomes at 18 months.
Conclusions:
- Structural and functional brain development in preterm infants is vulnerable to procedural pain and glucose exposure.
- Glucose administration for analgesia does not appear to mitigate the adverse effects of pain on brain development.
- Female preterm infants show distinct vulnerability to early pain compared to other neonatal morbidities.
- Procedural pain and glucose exposure have a lasting impact on neurodevelopment.
Abstract:
Our objectives were to determine whether procedural pain and glucose exposure are associated with altered structural and functional brain development differently in preterm males and females, and neurodevelopment at 18-month corrected age. Fifty-one very preterm neonates (22 males; median [interquartile range] gestational age 27.6 [2.0] weeks) underwent 3 serial scans including T1-weighted and resting-state functional magnetic resonance imaging (MRI) at median postmenstrual weeks: 29.4, 31.9, and 41.1. Thalamus, basal ganglia, and total brain volumes were segmented. Functional resting-state MRI data were extracted from the independent-components maps. Pain was operationalized as the total number of neonatal intensive care unit-administered invasive procedures. Neurodevelopmental outcomes at 18-month corrected age were assessed with the Bayley Scales of Infant Development, second edition. Generalized estimating equations assessed the association of pain and glucose exposure with brain structural and functional development. More invasive procedures were independently associated with slower growth of thalamic (P < 0.001), basal ganglia (P = 0.028), and total brain volumes (P = 0.001), particularly in females. Similar relationships were observed between glucose exposure and brain volumes. Functional connectivity between thalamus and sensorimotor cortices was negatively associated with number of invasive procedures. Greater procedural pain and higher glucose exposure were related to poorer neurodevelopmental outcomes. These findings suggest that structural and functional brain development is vulnerable to procedural pain. Glucose used for analgesia does not appear to mitigate the adverse impact of pain on brain development. The vulnerability of brain development in females towards early pain is distinct from other neonatal morbidities. The link between pain and glucose with neurodevelopment suggests that these factors have long-lasting impact.
