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Published on: November 20, 2015
Neuroinflammatory markers at school age in preterm born children with neurodevelopmental impairments
S Van der Zwart1, E F Knol2, P Gressens3
1Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Insights
Neonatal immune activation in preterm infants may lead to long-term neuroinflammation. School-aged preterm children with impairments show altered inflammatory profiles, with higher GM-CSF, Gal1, and TRAIL levels, indicating persistent immune system changes.
Area of Science:
- Neuroscience
- Immunology
- Developmental Pediatrics
Background:
- Neonatal immune system activation is linked to white matter injury in preterm infants.
- Animal studies suggest chronic immune activation and altered neuroinflammation persist years after preterm birth.
- The extent of these effects in humans remains largely unknown.
Purpose of the Study:
- To identify neuro-inflammatory markers at school age in preterm children.
- To correlate these markers with motor, cognitive, and behavioral impairments.
- To investigate differences in inflammatory profiles between preterm children with and without impairments.
Main Methods:
- A pilot case-control study included 20 preterm children (GA < 28 weeks) and 30 healthy adult controls.
- Thirty-nine inflammatory markers were measured in serum samples of preterm children at 8-9 years of age.
- Statistical analyses included comparisons to adult controls, univariate analysis for impairment groups, and principal component analysis.
Main Results:
- Inflammatory protein levels in preterm children differed significantly from adult controls.
- Preterm children with impairments exhibited higher levels of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) (p < 0.01).
- Trends towards significance were observed for Galectin-1 (Gal1) and TNF-Related Apoptosis-Inducing Ligand (TRAIL) in impaired preterm children.
Conclusions:
- The inflammatory profile in school-aged preterm children differs from adults.
- Elevated immune-modulating cytokines (GM-CSF, Gal1, TRAIL) in impaired preterm children suggest altered immune responses.
- Neuroinflammatory pathways appear to remain activated in preterm children with neurodevelopmental impairments even at school age.
Background:
Immune system activation in the neonatal period is associated with white matter injury in preterm infants. In animal studies, neonatal priming of the immune system leads to chronic activation of i.e. microglia cells and altered neuroinflammatory responses potentially years after preterm birth. This may contribute further to brain injury and neurodevelopmental impairment. It is unknown to what extend this also occurs in human.
Aim:
To identify neuro-inflammatory markers at school age that relate to motor, cognitive and behavioral impairments in preterm born children in a pilot case-control study.
Methods:
We included n = 20 preterm born children (GA < 28 weeks) in this study, of which n = 10 with motor, cognitive and behavorial impairments and n = 10 preterm born controls next to n = 30 healthy adult controls. In the preterm children, at 8-9 years, 39 inflammatory markers were assessed by Luminex assay in blood serum samples. Firstly, the preterm concentrations of these markers were compared to n = 30 adult controls. Then a univariate analysis was performed to determine differences in values between preterm children with and without impairment at school age. Finally, a principal component analysis and hierarchical clustering was performed to identify protein profiles in preterm born children that relate to impairment at school age.
Results:
Inflammatory proteins in preterm children at school age differed from values of adult controls. Within the group of preterm children, we found significantly higher levels of GM-CSF in preterms with impairment (p < 0.01) and a trend towards significance for Gal1 and TRAIL (p = 0.06 and p = 0.06 respectively) when compared to preterms without impairment. In addition, differences in clustering of proteins between preterm children was observed, however this variance was not explained by presence of neurodevelopmental impairments.
Conclusion:
The inflammatory profile at school age in preterm children is different from that of adult controls. The immune modulating cytokines GM-CSF, Gal1 and TRAIL were higher in preterm children with impairment than control preterm children, suggesting that immune responses are altered in these children. No specific cluster of inflammatory markers could be identified. Results indicate that even at school age, neuroinflammatory pathways are activated in preterm born children with neurodevelopmental impairments.
